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Methods for treating hyperlipidemia
The present application relates to a series of compounds, and pharmaceutical formulations thereof, of the formula ##STR1## which provide a method of inhibiting hyperlipidemia, especially hypercholesterolemia, and the pathological sequelae thereof, in mammals, including humans.
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The current invention relates to the fields of medicinal organic chemistry, pharmacology, and medicine. Further, the current invention relates to a group of known and novel compounds which demonstrate the potential for treating a pathological state known as hyperlipidemia in mammals, including humans.BACKGROUND OF THE INVENTION
Hyperlipidemia is a pathological state in mammals, where there is an abnormally high concentration of lipids circulating in the serum. The composition of the lipid pool in the circulation consists mostly of triglyceride (fatty acid esters of glycerol), cholesterol, and fatty acid esters of cholesterol. Such lipophillic molecules are poorly soluble in the aqueous environment of the serum and are, therefore, rarely found as free entities in the circulation. Such molecules are generally found bound to specific proteins in the form of complexes which act as transporting mechanisms. The specific, lipid carrying proteins are known as a class as apoproteins. Various combinations of different and specific lipids and apoproteins form particles (lipoproteins) which serve both to transport lipids and perform specific biological functions. In general, such particles are physically classified by their density, e.g., high density lipoproteins (HDL)--1.063-1.210 g/mL, low density lipoproteins (LDL)--1.019-1.063 g/mL, very low lipoproteins (VLDL)--<1.006 g/mL, etc. In addition, each of these particles contains a specific profile of lipid composition, e.g., HDL contains mostly cholesterol and its esters, whereas LDL's contain more or exclusively triglycerides.
Common pathological sequelae of hyperlipidemia, especially hypercholesterolemia, are atherosclerosis, hypertension, ischemic events, such as, myocardial infarction, cerebral stroke, and organ insufficiency and thrombosis.
A commonly used index of identifying human patients at risk of the pathological sequelae of hyperlipidemia, is the determination of total serum cholesterol. Generally, in adults, total serum cholesterol levels greater than 240 mg/dL are indicative of potential danger of hyperlipidemia, while levels <200 mg/dL are considered normal. As a rough measurement, these criteria are reasonably accurate. However, total cholesterol does not reflect the relative amounts or ratio of cholesterol in the various lipoproteins, e.g., HDL versus LDL. This ratio of the distribution of cholesterol has also been shown to correlate to the potential risk of developing cardiovascular disease due to hyperlipidemia. Thus, the total amount of cholesterol and its distribution are risk factors.
In a large and long epidemiologic study (Framingham Study), it was shown that hyperlipidemia, especially hypercholesterolemia, is a risk factor for atherosclerosis. However, this study also demonstrated that a high ratio of HDL to LDL decreases the chances of developing atherosclerosis. Therefore, in order to treat or prevent hyperlipidemia, this study suggests that it is more efficacious to both lower the total serum cholesterol and to raise the ratio of HDL to LDL than to only lower total cholesterol levels.
Many drugs are available which lower-total serum cholesterol, e.g., the chemical classes known as the statins. These agents have been useful in both treating and preventing hyperlipidemia. However, these agents have little or no effect on the ratio of HDL to LDL.
Agents or life-styles are known to effect the HDL-LDL ratio, e.g., exercise raises HDL, smoking lowers HDL, small amounts of alcohol raise HDL, and hormones may either raise or lower the ratio. Most germane, to the current invention, is the effect which estrogen has on the HDL-LDL ratio.
Premenopausal women, normally, have higher levels of HDL as than their male counterparts. Premenopausal women also have less cardiovascular disease, especially disease related to hyperlipidemia, as compared to males in the same age group. However, postmenopausal women, or women at the menopause, have an increased risk for cardiovascular disease sometimes even surpassing the risk of their male counterparts. At the menopause, women demonstrate a rapid rise in total serum cholesterol and a lowering of HDL. The exact mechanism of this change is not well understood; however, women, who receive Hormone Replacement Therapy, HRT, (estrogens and/or progestins), show a normalization of total serum cholesterol, HDL-LDL ratio, and a lessening in the risk of cardiovascular disease. Estrogen is believed to exert one of its cardiovascular protecting effects by increasing HDL levels.
Although there are many factors controlling the levels of HDL which are known, the entire control mechanism is not totally understood. One factor thought to be important in this process is the effect of hepatic lipase. Hepatic lipase, a liver enzyme, is a major factor in controlling the degradation of HDL particles. This enzyme facilitates the hydrolysis of HDL phospholipids and triglycerides and the subsequent dissolution of the lipoprotein particle. Recently, it has been found that the gene coding for this enzyme, controlled by many factors, is down-regulated by the hormone estrogen. This down-regulation of the lipase gene and subsequent lowering of the production of the enzyme, may, at least in part, explain the rise in HDL and lowering of cardiovascular risk in postmenopausal women on HRT. (For further information see: "Harrison's Principles of Internal Medicine", Eds. Iselbacher, et al., 9th Ed., McGraw-Hill Co., NYC, Chap. 250, pp. 1159-1168 and Chap.99, pp.507-518 and references therein; and Oka, K. et al., "Transcription of the human lipase gene is modulated by multiple negative elements in HepG2 cells.", Gene, 180, p.69-80 (1996) and references therein.)
Today, HRT is used in women to ameliorate the cardiovascular effects of menopause. This therapy, while effective, suffers from poor patient compliance, due to unpleasant side-effects, poor oral absorption, and poor bio-availability of the natural estrogens 17-b-estradiol and estrone.
Compounds of the current invention, i.e., the compounds of formula I(b), have the potential of down regulating the expression of hepatic lipase, thus raising the levels of HDL. This effect of raising HDL indicates usefulness in treating hyperlipidemia, especially hypercholesterolemia, and its subsequent pathological sequelae. In addition, compounds of the current invention are well absorbed by the oral route and possess favorable bio-availability properties.SUMMARY OF THE INVENTION
The current invention relates to compounds of formula I(a): ##STR2## where
R, R.sup.1, and R.sup.2 are independently at each occurrence hydrogen, hydroxy, or 13 O--Pg;
Pg is a hydroxy protecting group;
X is --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --, or --CH.dbd.CH--;
R.sup.3a is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or a moiety of the formula (a), (b), or (c): ##STR3## wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently at each occurrence hydrogen, fluoro, chloro, bromo, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or C.sub.1 -C.sub.4 alkoxy, with the proviso that, in the moiety of formula (a), R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 can not all be hydrogen;
or a pharmaceutically acceptable salt or solvate thereof.
Further, the current invention provides methods for inhibiting hyperlipidemia, especially hypercholesterolemia, and the pathological sequelae thereof, in mammals, including humans, which includes administering to a mammal in need thereof an effective amount of a compound of formula I(b): ##STR4## where
R.sup.a, R.sup.1a, and R.sup.2a are independently at each occurrence hydrogen, hydroxy, --O(C.sub.1 -C.sub.4 alkyl), --OCO(C.sub.1 -C.sub.4 alkyl), --OCOAr, --OCO.sub.2 (C.sub.1 -C.sub.4 alkyl), --OCO.sub.2 Ar, or C.sub.3 -C.sub.6 cycloalkoxy;
Ar is phenyl or substituted phenyl;
X is --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --, or --CH.dbd.CH--;
R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or a moiety of the formula (a), (b), or (c): ##STR5## wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently at each occurrence hydrogen, fluoro, chloro, bromo, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or C.sub.1 -C.sub.4 alkoxy;
or a pharmaceutically acceptable salt or solvate thereof.
Further the current invention includes pharmaceutical formulations, comprising a compound of formula I(a), where
--O--Pg is --O(C.sub.1 -C.sub.4 alkyl), --OCO(C.sub.1 -C.sub.4 alkyl), --OCOAr, --OCO.sub.2 (C.sub.1 -C.sub.4 alkyl), --OCO.sub.2 Ar, or C.sub.3 -C.sub.6 cycloalkoxy, and pharmaceutically acceptable excipients.DETAILED DESCRIPTION OF THE INVENTION
General chemical terms used in the description of compounds herein described bear their usual meanings. For example, "C.sub.1 -C.sub.4 alkyl" refers to a methyl, ethyl, propyl, iso-propyl, n-butyl, s-butyl, or a t-butyl group. The term, "C.sub.1 -C.sub.6 alkyl" would include the C.sub.1 -C.sub.4 alkyl in addition to straight or branched aliphatic chains of 5 or 6 carbon atoms, e.g., pentyl, 2-methylbutyl, hexyl, 2-methylpentyl, 3-methylpentyl, and the like. The term "C.sub.1 -C.sub.4 alkoxy" refers to a methoxy, ethoxy, propoxy, iso-propoxy, t-butoxy, s-butoxy, or a n-butoxy group. The term, "C.sub.3 -C.sub.6 cycloalkyl" means a cyclopropyl, cyclobutyl, cyclopentyl, or a cyclohexyl group. The term "C.sub.3 -C.sub.6 cycloalkoxy" refers to a cylclopropoxy, cyclobutoxy, cyclopentoxy or a cyclohexoxy group.
The symbol "Ar" refers to a phenyl or substituted phenyl group.
The term "substituted phenyl" refers to a phenyl group having one to three substituents selected from the group consisting of C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, hydroxy, nitro, chloro, fluoro, or tri(chloro or fluoro)methyl.
The term "halide" refers to chloro, bromo, or iodo.
The term "suitable solvent" refers to any solvent inert to the ongoing reaction that sufficiently solubilizes the reactants to effect the desired reaction.
The term "suitable kinetic base" refers to a strong base which provides a non-reversible deprotonation of an acidic substrate and is reactive enough to effect the desired reaction without significantly effecting any undesired reactions. Examples of kinetic bases include, but are not limited to, alkyl metals (e.g. n-butyl lithium, s-butyl lithium, and t-butyl lithium or ethyl magnesium bromide), metal amides such as lithium diisopropyl amide, metal alkoxides such as potassium t-butoxide, or metal hydrides (e.g. sodium, lithium, or potassium hydride).
The term "hydroxy protecting group" denotes a group understood by one skilled in the organic chemical arts of the type described in Chapter 2 of "Protective Groups in Organic Synthesis, 2nd Edition, T. H. Greene, et al., John Wiley & Sons, New York, 1991, hereafter "Greene".
Representative hydroxy protecting groups include, for example, C.sub.1 -C.sub.4 alkyl ether groups, including methyl, ethyl, or isopropyl ether; substituted C.sub.1 -C.sub.4 alkyl ether groups, including methoxymethyl ether, methylthiomethyl ether, tert-buylthiomethyl ether, (phenyldimethylsilyl)methoxymethyl ether, benzyloxymethyl ether, p-methoxy-benzyloxymethyl ether, and tert-butoxy-methyl ether; substituted ethyl ether groups such as ethoxyethyl ether, 1-(2-chloroethoxy)ethyl ether, 2,2,2-trichloroethoxymethyl ether, and 2-(trimethylsilyl)ethyl ether; and C.sub.3 -C.sub.6 cycloalkyl ether groups, including cyclopentyl ether and cyclohexyl ether; phenyl and substituted phenyl ether groups such as phenyl ether, p-chlorophenyl ether, p-methoxyphenyl ether, and 2,4-dinitrophenyl ether; benzyl ether groups such as benzyl ether; and alkylsilyl ether groups such as trimethyl-triethyl- and triisopropylsilyl ethers, mixed alkylsilyl ether groups such as dimethylisopropylsilyl ether, and diethylisopropylsilyl ether; and ester groups of the general formula CO.sub.2 C.sub.1 -C.sub.6 alkyl or CO.sub.2 Ar, or specific esters such as formate ester, benzylformate ester, mono- di- and trichloroacetate esters, phenoxyacetate ester, and p-chlorophenoxyacetate, and the like. Acyl groups of the general formula CO(C.sub.1 -C.sub.6 alkyl) or COAr and sulfonyl groups of the general formula SO.sub.2 R.sup.9, where R.sup.9 is Ar or C.sub.1 -C.sub.4 alkyl, are also encompassed within the definition of hydroxy protecting group.
In general, the species of hydroxy protecting group employed is not critical so long as the derivatized hydroxy group is stable to the condition of subsequent reaction(s) on other positions of the intermediate molecule and can be selectively removed at the appropriate point without disrupting the remainder of the molecule including any other hydroxy protecting group(s). However, the skilled artisan will recognize that the definition of R.sup.a, R.sup.1a, and R.sup.2a in compounds of formula I(b) includes hydroxy protecting groups which form a subset of the hydroxy protecting groups listed above. Thus, to carry out the methods of the invention, the species of hydroxy group is important and only those groups embodied within the method claims are operative. For purposes of synthesizing compounds of formula I(a) or I(b), it is within the knowledge of one skilled in the art to select appropriate hydroxy protecting group(s) for a given set of reaction conditions given the guidance provided by Greene cited above.
The term "pharmaceutically acceptable salt" refers to base addition salts of compounds of formula I(a) or I(b) which are known to be non-toxic and are commonly used in the pharmaceutical literature. Commonly used basic addition salts would be the salts formed by: alkali or alkaline earth hydroxides, ammonium hydroxide, sodium hydroxide, alkyl or aromatic amines, and the like.
By "pharmaceutically acceptable" it is also meant that the carrier, diluent, excipients and salt must be compatible with the other ingredients of the formulation, in addition to, not being deleterious to the recipient thereof.
The term "solvate" represents an aggregate that comprises one or more molecules of the solute, such as a formula I(a) or I(b) compound, with one or more molecules of solvent.
As used herein, the term "effective amount" means an amount of a compound of formula I(b) which is capable of alleviating the symptoms of the various pathological conditions herein described. The specific dose of a compound administered according to this invention will, of course, be determined by the particular circumstances surrounding the case including, for example, the compound administered, the route of administration, the state of being of the patient, and the pathological condition being treated.
The term "inhibit" bears its usual meaning which includes prohibiting, ameliorating, halting, restraining, slowing or reversing the progression, or reducing the severity of hyperlipidemia or a pathological symptom related to or resultant from hyperlipidemia, especially hypercholesterolemia. As such, these methods include both medical therapeutic (acute) and/or prophylactic (prevention) administration as appropriate.
Compounds of formula I (a) which encompass all the compounds of formula I (b) except those where R.sup.3 is a moiety of formula (a) wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are all hydrogen, may be synthesized by the routes illustrated in Scheme 1 and 2 below. Compounds of formula I(b), where R.sup.3 is a moiety of formula (a) where R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are all hydrogen, can be prepared by analogy to the methods discussed in Schemes 1 and 2 below. In Schemes 1 and/or 2, Halo, R, R.sup.1, R.sup.2, R.sup.3a are as described supra.
The compounds of formula I(a) where x is --CH.sub.2 -- (indenes) or --CH.sub.2 CH.sub.2 -- (dihydronapthalenes) may be synthesized by the route illustrated in Scheme 1 where n is 1 or 2. ##STR6##
The first step in the synthetic sequence is the cyclization of an appropriately substituted phenylpropionic acid or phenylbutyric acid of formula II in the presence of a strong dehydrating acid, e.g., polyphosphoric acid, concentrated sulfuric acid, and the like. Such reactions are usually carried out at elevated temperatures using either the acid e.g., polyphosphoric acid, or a high boiling, inert liquid as a solvent, e.g., chlorobenzene, toluene, and the like. Such reactions are usually complete in two to twenty hours when conducted at temperatures above 100.degree. C. This step yields the indanones (n=1) and tetralones (n=2) of formula III.
The compounds of formula III may be converted to the diketones of formula V by installation of a benzoyl moiety onto a compound of formula III. This conversion is accomplished by dissolving or suspending a compound of formula III in a suitable solvent and adding a suitable kinetic base to form the corresponding anion. A preferred kinetic base is typically an alkaline metal amide such as lithium amide. Suitable solvents include, but are not limited to tetrahydrofuran, ether, hexane, methylene chloride, mixtures thereof, and the like. Tetrahydrofuran is typically the preferred solvent. The deprotonation is generally run at temperatures from ambient to -50.degree. C., preferably at 0.degree. C. Once the anion is formed, typically in about ten minutes at 0.degree. C., a compound of formula IV may be added directly to the cold anion solution to yield, after stirring at ambient temperature for about 2 hours, a diketone of formula V.
Compounds of formula I(c) may be prepared from a commercially available Grignard reagent of formula VI and a compound of formula V. The Grignard reagent may alternatively be made by dissolving a commercially available compound of the formula R.sup.3 -Halide in the presence of magnesium and mercury (II) chloride in a mutually inert solvent. Once the Grignard reagent is formed, a diketone of formula V may be added to provide the intermediate alcohol of formula VII. Of the standard Grignard reagents known in the art, the magnesium bromide would be preferred. The compound of formula VI is generally employed in a substantial molar excess, for example in from a three molar excess to about a ten molar excess relative to the compound of formula V, preferably in about a 5 molar excess. Typical solvents suitable for use in this reaction include tetrahydrofuran but diethyl ether is preferred. The reaction is generally substantially complete after about 1 to 24 hours when conducted at a temperature in the range of from about ambient to the reflux temperature of the reaction mixture. The reaction is preferably conducted under controlled reflux conditions for about 2 to 6 hours. The alcohol of formula VII is typically dehydrated under the conditions of its formation described above to yield the compound of formula I(c).
The compounds of formula I(a) where X is --CH.sub.2 .dbd.CH.sub.2 -- (naphthalenes) may be prepared by oxidation of dihydronaphthalene derivatives of formula I(d), as illustrated in Scheme 2 below. ##STR7##
Compounds of formula I(e) may be prepared by dissolving or suspending a compound of formula I(d) (i.e. a compound of formula I(c) where n is 2) in a suitable solvent and adding an oxidant. Choices of oxidants and solvents may be found in Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, N.Y., 1989, pg. 95. A preferred oxidant is 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Benzene or toluene is the preferred solvent. While the amount of oxidant employed will vary with the particular oxidant, when DDQ is the oxidant, it is employed in a molar excess. For example, a 1.2 to a 1.6 molar excess, relative to the compound of formula I(d), is usually employed. A 1.3 molar excess is typically preferred. This reaction is most often run at temperatures between 25.degree. C. and 125.degree. C. and is preferably run at about 80.degree. C. Under these conditions, the reaction is usually completed in one to twenty hours.
When any of R, R.sup.a, R.sup.1, R.sup.1a, R.sup.2, or R.sup.2a are hydroxy protecting groups in compounds of formula I(a) or I(b), they may be removed by well known methods in the art. Numerous reactions for the formation and removal of the hydroxy protecting groups contemplated within the scope of this invention are described in a number of standard works including, for example in The Peptides, Vol. I, Schrooder and Lubke, Academic Press (London and New York, 1965) or in Greene. Methods for removing preferred hydroxy protecting groups, particularly methyl groups, are essentially as described in Example 2 infra. In addition, if compounds of formula I(a) contain a hydroxy protecting group(s) which is not operative in the methods of the current invention, it may be removed and an operative hydroxy protecting group(s) may be installed as described in Greene or as described in the paragraph below.
Compounds of formula I(a) or I(b), where R, R.sup.a, R.sup.1, R.sup.1a, R.sup.2, or R.sup.2a are acyl derivatives of the free phenols, may be obtained by removal of the non-acyl hydroxy protecting groups when present and acylation with the appropriate acylating agent. Compounds of formula I(a), where R, R.sup.1, and R.sup.2 are sulfonyl derivatives of the free phenols, may be obtained by removal of the non-sulfonyl hydroxy protecting groups when present and sulfonation with the appropriate sulfonating agent. Methods for the acylation or sulfonation of the deprotected compounds is essentially revealed in U.S. Pat. No. 4,358,593, the teachings of which are herein incorporated by reference.
For specific instruction on the synthesis of compounds of formula I(b) where R.sup.3 is phenyl see U.S. Pat. No. 4,075,227 the teaching of which are hereby incorporated by reference.
The optimal time for performing the reactions of Schemes 1 and 2 can be determined by monitoring the progress of the reaction via conventional chromatographic techniques. Furthermore, it is preferred to conduct the reactions of the invention under an inert atmosphere, such as, for example, argon, or, particularly, nitrogen. Choice of solvent is generally not critical so long as the solvent employed is inert to the ongoing reaction and sufficiently solubilizes the reactants to effect the desired reaction. Intermediate and final products may be purified, if desired by common techniques such as recrystallization or chromatography over solid supports such as silica gel or alumina.
Compounds of formula III, IV, and VI are either commercially available or may be prepared by methods well known in the art.
Application of the above chemistry enables the synthesis of the compounds of formula I(a), which include, but is not limited to:
1-(2-isopropoxyphenyl)-2-(4-methoxybenzoyl)-3,4-dihydro-6-methoxynaphthalen e;
1-(2-hydroxyphenyl)-2-(4-acetyloxybenzoyl)-3,4-dihydro-6-hydroxynaphthalene ;
1-(2,4-difluorophenyl)-2-(3-hydroxybenzoyl)-3,4-dihydro-6,7-dihydroxynaphth alene;
1-(2,3,4,5,6-pentafluorophenyl)-2-(4-acetyloxybenzoyl)-6-hydroxynaphthalene ;
1-methyl-2-(4-cyclopentyloxybenzoyl)-6-hydroxynaphthalene; and the like.
The following examples are provided for the purpose of illustrating the preparation of the compounds of the current invention and are not intended to limit its scope.
In the following Preparations and Examples, the terms melting point, proton nuclear magnetic resonance spectra, electron impact mass spectra, elemental analysis, high performance liquid chromatography, and thin layer chromatography are abbreviated "mp", ".sup.1 H NMR", "MS(EI)", "EA", "HPLC", and "TLC", respectively. The values reported for MS(EI) correspond to mass numbers unless otherwise indicated.Preparations Preparation 1 1-Oxo-5-Methoxyindane
A mixture of 5 g of 3-(3-methoxyphenyl)propionic acid in polyphosphoric acid was prepared. The mixture was heated for 2 hours at 120.degree. C. The mixture was cooled and ice was added. The resulting solid was removed by filtration and dissolved in benzene. The benzene solution was filtered and concentrated to one-fourth its original volume. Petroleum ether was added and the mixture was cooled to 5.degree. C. The product was collected by filtration.
mp: 105.degree. C.-107.degree. C. EA: Calc. for C.sub.10 H.sub.10 O.sub.2 : C, 74.06; H, 6.22; O, 19.73. Found: C, 74.32; H, 6.42; O, 20.03.Preparation 2 1-Oxo-2-(4-Methoxybenzoyl)-5-Methoxyindane
A solution of 22.2 g (137 mmol) of 1-oxo-5-methoxyindane in tetrahydrofuran was added dropwise to a cold suspension of 11 g (274 mmol) of sodium amide in tetrahydrofuran. The resulting mixture was stirred for ten minutes and a solution of 31.3 g (137 mmol) of phenyl-4-methoxybenzoate in tetrahydrofuran was added. Cooling was discontinued and a slight exothermic reaction occurred. The mixture was stirred at ambient temperature for an additional two hours. A thick precipitate developed and the reaction mixture was poured into ice-water. The aqueous mixture was extracted with ethyl acetate. The ethyl acetate extract was evaporated to dryness to obtain 20.7 g of the title compound. mp: 160.degree. C.-162.degree. C.Preparation 3 2-(4-Methoxybenzoyl)-6-Methoxy-a-Tetralone
To a suspension of 10.5 g of sodium amide in tetrahydrofuran was added 23.2 g of 6-methoxy-a-tetralone in tetrahydrofuran. The resulting mixture was stirred for ten minutes and a solution of 30 g of phenyl 4-methoxybenzoate in tetrahydrofuran was added. The reaction was allowed to proceed for sixteen hours at ambient temperature. The reaction was concentrated in vacuo and water was added to the residue. The mixture was filtered and the residue slurried in hot methanol. The hot methanol was allowed to cool and 24.3 g of the title compound crystallized out.
mp: 112.degree. C.-113.degree. C. EA: Calc. for C.sub.19 H.sub.18 O.sub.3 : C, 75.53; H, 5.85; 0, 20.62. Found: C, 72.23; H, 6.55, 0, 20.67. MS(EI): 310 (M+).EXAMPLES EXAMPLE 1 2-(4-Methoxybenzoyl)-3-Phenyl-6-Methoxyindene
A slurry of 20.5 g (97 mmol) of 1-oxo-2-(4-methoxybenzoyl)-5-methoxyindane in benzene was added as a slow stream to a solution of a five-fold excess of phenylmagnesium bromide in ether. The resulting mixture was heated to reflux for four hours, cooled, and poured into a mixture of ice-sulfuric acid. The mixture was extracted with ethyl acetate. The ethyl acetate extract was washed with water, then with aqueous sodium bicarbonate solution, and dried over magnesium sulfate. After filtering, the mixture was concentrated to 28 g of a dark red oil. A mixture of 20% ether in methanol (25 mL) was added. Part of the oil crystallized on standing at ambient temperature and was isolated by filtration to obtain 7.5 g of red crystals. This material was slurried in a hot mixture of benzene and acetone. The insoluble solid was separated by filtration. The filtrate was concentrated to dryness and the residue was crystallized from ether to obtain 5.4 g of the title compound. The filtrate from the aforementioned separation of the red crystals was concentrated and chromatographed on a silica gel column eluted with benzene. From the chromatography was obtained an additional 3 g of the title compound. These two portions of the product were combined and recrystallized from acetone to yield the final form of the title compound.
mp: 115-116.degree. C. EA: Calc. for C.sub.24 H.sub.20 O.sub.3 : C, 80.88; H, 5.66; O, 13.47. Found: C, 80.95; H, 5.84; O, 14.42.EXAMPLE 2 2-(4-Methoxybenzoyl)-3-Phenylindene
A slurry of 13.25 g (50 mmol) of 1-oxo-2-(4-methoxybenzoyl)indane in a mixture of 300 mL of ether and 300 mL of benzene was prepared. To the slurry was added 35.66 g (197 mmol) of phenylmagnesium bromide. The resulting mixture was heated to reflux for sixteen hours and poured into a mixture of ice and sulfuric acid. The mixture was allowed to separate and the organic layer was removed. The organic extract was washed with a bicarbonate solution, dried over sodium sulfate, filtered, and concentrated to a red oil. A small amount of ether was added to the oil and a crystalline precipitate formed. The crystals were removed by filtration. The filtrate was concentrated to dryness and the product crystallized from methanol to yield 9.3 g of the title compound.
mp: 114.degree. C.-115.degree. C. EA: Calc. for C.sub.23 H.sub.18 O.sub.2 : C, 84.64; H, 5.56; O, 9.80. Found: C, 84.69; H, 5.82; O, 9.79.EXAMPLE 3 2-(4-Hydroxybenzoyl)-3-Phenyl-6-Hydroxyindene
To a solution of 4 g of 2-(4-methoxybenzoyl)-3-phenyl-6-methoxyindene in methylene chloride was added two equivalents of boron tribromide. The resulting mixture was stirred for twenty four hours at ambient temperature. Monitoring of the reaction by TLC indicated a small amount of mono-methoxy compound present, therefore, an additional equivalent of boron tribromide was added and the reaction was allowed to proceed for seventy-two hours. The reaction was concentrated to dryness and chromatographed on a silica gel column eluted with a solvent mixture of benzene:ethyl acetate (9:1)(v/v). This yielded 3 g of the title compound.
mp: 191.degree. C.-192.degree. C. EA: Calc. for C.sub.22 H.sub.16 O.sub.3 : C, 80.47; H, 4.91; O, 14.62. Found: C, 80.28; H, 4.98; O, 14.71.EXAMPLE 4 1-Phenyl-2-(4-Methoxybenzoyl)-3,4-Dihydro-6-Methoxynaphthalene
To 500 mL of a 1:1 mixture of ether and benzene was added 21.7 g (70 mmol) of 2-(4-methoxybenzoyl)-6-methoxy-a-tetralone. To this slurry was added 146 mL of 2.05 molar solution (300 mmol) of phenylmagnesium bromide in ether. The green reaction mixture was heated to reflux for four hours and then poured into a mixture of ice/sulfuric acid. The slurry was extracted with ethyl acetate. The ethyl acetate extract was washed with water, bicarbonate solution, then again with water, and finally dried over magnesium sulfate. The extract was filtered then evaporated to a red-yellow oil. The product oil was crystallized from ether to yield 13.8 g of the title compound as a white solid.
mp: 107.degree. C.-108.degree. C. EA: Calc. for C.sub.25 H.sub.22 O.sub.3 : C, 81.06; H, 5.99; O, 12.96. Found: C, 81.14; H, 5.79; O, 12.93. MS(EI): 370 (M+).EXAMPLE 5 1-Phenyl-2-(4-Hydroxybenzoyl)-3,4-Dihydro-6-Hydroxynaphthalene
To a cold 300 mL of dimethylformamide and under a nitrogen atmosphere was added 9.3 g of ethylmercaptan. To this mixture was added 7.2 g of 50% sodium hydride (150 mmol) in oil. To this mixture was added 11.1 g (30 mmol) of 1-phenyl-2-(4-methoxybenzoyl)-3,4-dihydro-6-methoxynaphthalene and the reaction mixture was heated to 60.degree. C. for two hours. The reaction was acidified with the addition of 1N hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extract was washed with water and evaporated to dryness. The final product was crystallized from a mixture of methanol-acetone to yield 8 g of the title compound.
mp: 205.degree. C.-207.degree. C. EA: Calc. for C.sub.23 H.sub.18 O.sub.3 : C, 80.68; H, 5.30; O, 14.02 Found: C, 80.38; H, 5.43; O, 14.28.EXAMPLE 6 1-Phenyl-2-(4-Methoxybenzoyl)-6-Methoxynaphthalene
To 11.1 g (30 mmol) of 1-phenyl-2-(4-methoxybenzoyl)-3,4-dihydro-6-methoxynaphthalene dissolved in benzene was added DDQ (9 g, 40 mmol). The mixture was heated to reflux for two hours and filtered while hot through silica gel. The silica gel was washed three times with ethyl acetate. The ethyl acetate washings and the benzene solution were combined and evaporated to dryness. The residue was crystallized from hot methanol, which yielded 4.5 g of the title compound.
mp: 122.degree. C.-124.degree. C. EA: Calc. for C.sub.25 H.sub.18 O.sub.3 : C, 80.86; H, 5.30; O, 14.02. Found: C, 80.83; H, 5.68; O, 12.93. MS(EI): 368 (M+).
The following examples demonstrating the methods of the current invention are given for the purpose of illustration and are not meant to be limiting in any way.Assay 1
Seventy-five day old female Sprague Dawley rats (weight range of 200 g to 225 g) were obtained from Charles River Laboratories (Portage, Mich.). The animals were either bilaterally ovariectomized (OVX) or exposed to a Sham surgical procedure at Charles River Laboratories, and then shipped after one week. Upon arrival, they were housed in metal hanging cages in groups of 3 or 4 per cage and had ad libitum access to food (calcium content approximately 0.5%) and water for one week. Room temperature was maintained at 22.2.degree..+-.1.7.degree. C. with a minimum relative humidity of 40%. The photoperiod in the room was 12 hours light and 12 hours dark.
Dosing Regimen Tissue Collection. After a one week acclimation period (therefore, two weeks post-OVX) daily dosing with test compound was initiated. 17a-ethynyl estradiol or the test compound were given orally, unless otherwise stated, as a suspension in 1% carboxymethylcellulose or dissolved in 20% cyclodextrin. Animals were dosed daily for 4 days. Following the dosing regimen, animals were weighed and anesthetized with a ketamine: Xylazine (2:1, V:V) mixture and a blood sample was collected by cardiac puncture.
Cholesterol Analysis. Blood samples were allowed to clot at room temperature for 2 hours, and serum was obtained following centrifugation for 10 minutes at 3000 rpm. Serum cholesterol was determined using a Boehringer Mannheim Diagnostics high performance cholesterol assay. Briefly the cholesterol was oxidized to cholest-4-en-3-one and hydrogen peroxide. The hydrogen peroxide was then reacted with phenol and 4-aminophenazone in the presence of peroxidase to produce a p-quinone imine dye, which was read spectrophotemetrically at 500 nm. Cholesterol concentration was then calculated against a standard curve. The entire assay was automated using a Biomek Automated Workstation.
A representative compound of the current invention, when assayed by this method, gave the positive results reported in Table 1 below.
TABLE 1 ______________________________________ Serum Cholesterol Compound (% decrease vs Control) ______________________________________ 1-phenyl-2-(4-methoxybenzoyl)- 75.3* @ 0.1.sup.a 6-methoxynaphthalene 71* @ 1.0.sup.a (Compound of Example 6) 53.3* @ 10.0.sup.a 17a-ethynylestradiol 78.4* @ 0.1.sup.a ______________________________________ .sup.a Dose in mg/kg P.O. *p < 0.05Assay 2
Forty-one to forty-three day old Sprague Dawley male rats (weight range 200 g to 225 g) were obtained from Harlan (Indianapolis, Ind.). Upon arrival, the animals were housed in metal hanging cages with 6 or 7 animals per cage, with access to food and water, ad libitum. After one or two days, the animals were housed individually, ambient temperature was maintained at 22.2.degree. C. with a relative humidity of 40%. The photoperiod in the room was 12 hours of dark and 12 hours of light.
Dosing Regimen Tissue Collection. After a one week acclimation period daily dosing with the test compounds or standards was initiated. The animals were weighed after two days of dosing and the doses were adjusted for any change in the animals weight. All compounds were given by oral gavage in a formulation of 0.5 mL of 1% aqueous carboxymethylcellulose. The animals were dosed for four days. At the end of the dosing period, the animals were weighed and rendered unconscious with carbon dioxide. Blood samples were collected by cardiac puncture into EDTA treated tubes and a portion of the liver was removed and rapidly frozen Liver portions were stored at -80.degree. C. in liquid nitrogen for further analysis.
Lipid Analysis. Plasma was obtained by centrifugation of the blood sample for 10 minutes at 2500 rpm. Plasma cholesterol was determined using a WAKO Diagnostic Cholesterol II Assay.
Hepatic Lipase Assay. A portion of the liver was homogenized in normal saline containing 20 units of heparin per mL. After a 30 minute incubation at ambient temperature, the homogenate was centrifuged for 3 minutes at 8000 g, and the supernatant collected for assay. Hepatic lipase activity was determined essentially by the method of Henderson et al., using H.sup.3 triolein in an acacia emulsion as a substrate. Free fatty acids were separated from non-hydrolyzed substrate by the addition of fumed silica according to Borensztajn et al. and quantitated by liquid scintillation. (See: Henderson, A. D., Richmond, W., and Elkeles, R. S., "Hepatic and Lipoprotein Lipases Selectively Assayed in Postheparin Plasma.", Clin. Chem., 39/2, p. 218-223 (1993). Borensztajn, J., Reddy, M. N., and Gladstone, A. R., "A Simple Method for the Separation of Triacylglycerols from Fatty Acids Released in Lipase Assays.", J. Lipdid Res., 29, p. 1549-1552 (1988).)
Positive results using representative compounds of the current invention demonstrate the potential for the methods of the current invention.
The compounds of this invention can be administered by a variety of routes including oral, rectal, transdermal, subcutaneous, intravenous, intramuscular, and intranasal. These compounds preferably are formulated prior to administration, the selection of which will be decided by the attending physician. Thus, another aspect of the present invention is a pharmaceutical formulation comprising an effective amount of a compound of formula I(a), where R, R.sup.1, and R.sup.2 are independently at each occurrence hydrogen, hydroxy, --O(C.sub.1 -C.sub.4 alkyl), --OCO(C.sub.1 -C.sub.4 alkyl), --OCOAr, --OCO.sub.2 (C.sub.1 -C.sub.4 alkyl), --OCO.sub.2 Ar, or C.sub.3 -C.sub.6 cycloalkoxy; or a pharmaceutically acceptable salt thereof, (hereafter referred to as compounds of formula I(f)) and a pharmaceutical carrier, diluent, or excipient.
The total active ingredients in such formulations comprises from 0.1% to 99.9% by weight of the formulation. A typical daily dose will contain a nontoxic dosage level of from about 1 mg to about 600 mg/day of a compound of formula I(f) or I(b). Preferred daily doses generally will be from about 5 mg to about 80 mg/day.
Pharmaceutical formulations of the present invention can be prepared by procedures known in the art using well known and readily available ingredients. For example, the compounds of formula I(f) can be formulated with common excipients, diluents, or carriers, and formed into tablets, capsules, suspensions, powders, and the like. Examples of excipients, diluents, and carriers that are suitable for such formulations include the following: fillers and extenders such as starch, sugars, mannitol, and silicic derivatives; binding agents such as carboxymethyl cellulose and other cellulose derivatives, alginates, gelatin, and polyvinyl-pyrrolidone; moisturizing agents such as glycerol; disintegrating agents such as calcium carbonate and sodium bicarbonate; agents for retarding dissolution such as paraffin; resorption accelerators such as quaternary ammonium compounds; surface active agents such as cetyl alcohol, glycerol monostearate; adsorptive carriers such as kaolin and bentonite; and lubricants such as talc, calcium and magnesium stearate, and solid polyethyl glycols.
Compounds of formula I(f) also can be formulated as elixirs or solutions for convenient oral administration or as solutions appropriate for parenteral administration, for example, by intramuscular, subcutaneous or intravenous routes. Additionally, the compounds are well suited to formulation as sustained release dosage forms and the like. The formulations can be so constituted that they release the active ingredient only or preferably in a particular physiological location, possibly over a period of time. The coatings, envelopes, and protective matrices may be made, for example, from polymeric substances or waxes.
Compounds of formula I(b) and I(f), generally, will be administered in a convenient formulation as determined by the attending physician. The following formulation examples are only illustrative and are not intended to limit the scope of the present invention.Formulations
In the formulations which follow, "active ingredient" means a compound of formula I(f), or a pharmaceutically acceptable salt or solvate thereof.
Hard gelatin capsules are prepared using the following:
______________________________________ Formulation 1 Gelatin Capsules Ingredient Quantity (mg/capsule) ______________________________________ Active ingredient 0.1-1000 Starch, NF 0-650 Starch flowable powder 0-650 Silicone fluid 350 centistokes 0-15 ______________________________________
The formulation above may be changed in compliance with the reasonable variations provided.
A tablet formulation is prepared using the ingredients below:
______________________________________ Formulation 2 Tablets Ingredient Quantity (mg/tablet) ______________________________________ Active ingredient 2.5-1000 Cellulose, microcrystalline 200-650 Silicon dioxide, fumed 10-650 Stearate acid 5-15 ______________________________________
The components are blended and compressed to form tablets.
Alternatively, tablets each containing 2.5-1000 mg of active ingredient are made up as follows:
______________________________________ Formulation 3 Tablets Ingredient Quantity (mg/tablet) ______________________________________ Active ingredient 25-1000 Starch 45 Cellulose, microcrystalline 35 Polyvinylpyrrolidone 4 (as 10% solution in water) Sodium carboxymethyl cellulose 4.5 Magnesium stearate 0.5 Talc 1 ______________________________________
The active ingredient, starch, and cellulose are passed through a No. 45 mesh U.S. sieve and mixed thoroughly. The solution of polyvinylpyrrolidone is mixed with the resultant powders which are then passed through a No. 14 mesh U.S. sieve. The granules so produced are dried at 50.degree. C.-60.degree. C. and passed through a No. 18 mesh U.S. sieve. The sodium carboxymethyl starch, magnesium stearate, and talc, previously passed through a No. 60 U.S. sieve, are then added to the granules which, after mixing, are compressed on a tablet machine to yield tablets.
Suspensions each containing 0.1-1000 mg of medicament per 5 ml dose are made as follows:
______________________________________ Formulation 4 Suspensions Ingredient Quantity (mg/5 ml) ______________________________________ Active ingredient 0.1-1000 mg Sodium carboxymethyl cellulose 50 mg Syrup 1.25 mg Benzoic acid solution 0.10 mL Flavor q.v. Color q.v. Purified water to 5 mL ______________________________________
The medicament is passed through a No. 45 mesh U.S. sieve and mixed with the sodium carboxymethyl cellulose and syrup to form a smooth paste. The benzoic acid solution, flavor, and color are diluted with some of the water and added, with stirring. Sufficient water is then added to produce the required volume.
An aerosol solution is prepared containing the following ingredients:
______________________________________ Formulation 5 Aerosol Ingredient Quantity (% by weight) ______________________________________ Active ingredient 0.25 Ethanol 25.75 Propellant 22 (Chlorodifluoromethane) 70.00 ______________________________________
The active ingredient is mixed with ethanol and the mixture added to a portion of the propellant 22, cooled to 30.degree. C., and transferred to a filling device. The required amount is then fed to a stainless steel container and diluted with the remaining propellant. The valve units are then fitted to the container.
Suppositories are prepared as follows:
______________________________________ Formulation 6 Suppositories Ingredient Quantity (mg/suppository) ______________________________________ Active ingredient 250 Saturated fatty acid 2,000 glycerides ______________________________________
The active ingredient is passed through a No. 60 mesh U.S. sieve and suspended in the saturated fatty acid glycerides previously melted using the minimal necessary heat. The mixture is then poured into a suppository mold of nominal 2 g capacity and allowed to cool.
An intravenous formulation is prepared as follows:
______________________________________ Formulation 7 Intravenous Solution Ingredient Quantity ______________________________________ Active ingedient 50 mg Isotonic saline 1,000 mL ______________________________________
The solution of the above ingredients is intravenously administered to a patient at a rate of about 1 ml per minute.
1. A method of inhibiting hyperlipidemia comprising administering to a mammal in need thereof an effective amount of a compound of formula I(b): ##STR8## where R.sup.a, R.sup.1a, and R.sup.2a are independently at each occurrence hydrogen, hydroxy, --O(C.sub.1 -C.sub.4 alkyl), --OCO(C.sub.1 -C.sub.4 alkyl), --OCOAr, --OCO.sub.2 (C.sub.1 -C.sub.4 alkyl), --OCO.sub.2 Ar, or C.sub.3 -C.sub.6 cycloalkoxy;
- Ar is phenyl or substituted phenyl;
- X is --CH.sub.2 --, --CH.sub.2 --CH.sub.2 --, or --CH.dbd.CH--;
- R.sup.3 is hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or a moiety of the formula (a), (b), or (c): ##STR9## wherein R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are independently at each occurrence hydrogen, fluoro, chloro, bromo, C.sub.1 -C.sub.4 alkyl, C.sub.3 -C.sub.6 cycloalkyl, or C.sub.1 -C.sub.4 alkoxy;
2. A method according to claim 1 wherein said mammal is a human.
3. A method according to claim 2 wherein said human is female.
4. A method according to claim 3 wherein said female is post-menopausal.
5. A method according to either claim 2 or claim 3 wherein the hyperlipidemia is hypercholesterolemia.
6. A method according to either claim 2 or claim 3 wherein the hyperlipidemia results in atherosclerosis.
7. A method according to claim 2 wherein said compound of formula I(b) is a compound wherein R.sup.2a is not hydrogen and R.sup.1a is hydrogen.
8. A method according to claim 7 wherein said compound of formula I(b) is a compound wherein R.sup.3 is a moiety of formula (a) and R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.8 are all hydrogen.
9. A method according to claim 8 wherein R.sup.a and R.sup.2a are both methoxy.
10. A method according to claim 8 wherein R.sup.a and R.sup.2a are both hydroxy.
11. A method according to claim 2 wherein said compound of formula I(b) is 1-phenyl-2-(4-methoxybenzoyl)-6-methoxynaphthalene.
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- Crenshaw, R.R., et al., Potential Antifertility Agents, J. Med. Chem. vol. 14, No. 12, pp. 1185-1190 (1971). Jones, C.D., et al., Antiestrogens, J. Med. Chem. vol. 27, pp. 1057-1066 (1984). Jones, C.D., et al., Antiestrogens, J. Med. Chem. vol. 35, pp. 931-938 (1992). Silvestri et al, Antifungal agents; Farmaco, 50(4), pp. 227-238, 1995.
Type: Grant
Filed: Aug 4, 1998
Date of Patent: Aug 22, 2000
Assignee: Eli Lilly and Company (Indianapolis, IN)
Inventor: George Joseph Cullinan (Trafalgar, IN)
Primary Examiner: Sreeni Padmanabhan
Attorney: Scott Alexander McNeil
Application Number: 9/128,875
International Classification: A61K 3112;


text:
Sunday, December 24, 2006
My brother Jeff, and his fiance Tara. What a beautiful new sister I am getting!
My niece and nephews
Me and one of my brown-eyed boys!
For some reason I have an annual tradition of neglecting to send Christmas cards. Mostly it is because I have either recently moved, been out of the country - making it difficult to send cards, or simply failed to buy them. So for those of you who keep up with this blog, consider this my Christmas greeting and "life update" all wrapped into one.
This year I am celebrating Christmas with my family - who is now much closer than several states away. I am rejoicing that my life in Texas has been full of old friends and new ones. I am grateful for the many ways God has shown His love and faithfulness to me this year. It has been a good year full of travels and transition. I've had the opportunity to finish a season as a college professor, lead 25 high school students on an international experience, involve myself in a great community of believers in Texas, celebrate my 30th birthday alongside my nine-year-old niece, begin sewing lessons with my grandmother, and start a career as an event planner. It has been an eventful year indeed.
I am truly grateful to look back over this past year and remember that God has given an abundance of good things. May this season be a reminder of how beautiful, precious, and REAL He is.
I pray He is adored by you and yours today, tomorrow, and always.
Sunday, November 26, 2006
Dinosaur Bones.
Over the holiday I took my nephews to the Science Museum in Fort Worth. Aren't they cute? And surprisingly brave to pose in front of this very patient dinosaur?
Matthew loved digging for dinosaur bones in the designated sand pit out front. He kept screaming, "Aunt Nicole, I found something!" Every time I would walk over and inspect the rock he was holding and reassure him that, yes, I think he may have been a part of uncovering a very important artifact. The museum is very gracious to allow 7-year-olds to host their own archaeological digs of sorts out front. I'll bet they don't even notice that kids everywhere are taking home pocketfuls of rocks they are convinced belonged to an ancient dinosaur.
If you are in Fort Worth and want to check it out, you too can take home your very own piece of dinosaur bone - or rocks. Whichever ones you are lucky enough to find.
...Leslie Roberson. She has displayed her party expertise yet again. Check it out. At first glance, it looks like my ipod that got left on the kitchen table...
But look more closely and you'll see that it's a party invitation wrapped up in chocolate. I'm telling you, she should copyright this stuff.
Long Overdue: WE WON
For you faithful blog readers who wondered about the fate of Kelly and I's entry in the pumpkin carving contest - good news! We won. Here's a picture of our reward. We promptly split it up to be used for dinner out or some other unbudgeted entertainment activity. Fantastic!
Wednesday, November 22, 2006
Many of you, if you keep up with global news regarding Christian persecution, have heard about a recent case in Turkey. Two guys I worked closely with in Istanbul have been arrested and are facing a trial tomorrow that could result in a prison sentence.
Hakan and Turan, both Turkish and Christian, were charged initially with illegal gun possession (a totally false accusation) and now face three charges: 1)Article 301-Putting down the Turkish republic and inciting riot 2) Article 216-Saying bad things about another person's religion, 3) Article 135-Gathering and using people's personal information with out their permission.
Hakan and Turan are working along with other Christians in Turkey to send out Bible correspondence information to people who request it. This is not illegal. Being a Christian is not illegal….but these two were targeted by the local community and the government. They are being charged with offenses that are not true and prosecuted under Turkish laws that have received a lot of scrutiny lately as Turkey vies for EU membership.
The outcome of this case could be a very important factor as the EU watches how Turkey treats minorities. These laws don't just affect Turkish Christians, they affect writers, artists, and other religious minorities in Turkey. In fact, anyone who might say anything that seems to go against the strong nationalism/Islamic heritage of Turkey can be a target. Several people have been arrested under these laws. If you'd like to read more about the political details of the law and how it affects people in Turkey, check out this wikipedia article.
How should we respond? As people who live in a country where there is freedom of speech and freedom of religion, our first response should be gratitude. Not one of us has to be concerned that sharing our faith will land us in prison in the US. Secondly, if you are a follower of Christ, pray for these brothers and their families. They have displayed tremendous faith and are not worried about their situation. In fact, Turan wrote a recent email that said pray he will face these trials as Paul did, with boldness and faith. The outcome of this trial could affect the Church in Turkey and how Christians are treated in places where Christ is not known. May we recognize our responsibility as the Church to be involved, to pray, and stay informed about what's going on around the globe.
Tuesday, October 31, 2006
The women sitting at Leslie Roberson's beautifully decorated fall table.
Nick & Traci - friends and neighbors
Leslie's Centerpiece
Nicole & Amy
Callie, Amy, Amanda & Sylvia
Sunday, October 29, 2006
At work on Friday we had a pumpkin carving contest and "Autumn" is what my co-worker and I came up with.
Here are some of the reasons we decided to forego the traditionally carved pumpkin:
1. There is a lot of pressure to come up with an original carving design. This natural pumpkin idea came from google. Not hard at all.
2. Cutting a pumpkin with a knife is hard. Hot gluing acorns and gourds seemed much easier.
3. It's messy to dig out the inside of a pumpkin. Sorry, co-workers, but I'm not willing to get messy at work for the sake of winning a contest.
4. We can label our pumpkin "made with all natural ingredients".
5. Since the contest was on Friday and the pumpkins are hanging around till Tuesday, we know ours isn't going to rot. Rotten pumpkins are stinky. And they attract flies too.
Here's to hoping Autumn wins the contest!
Tuesday, October 17, 2006
This is a picture of me and Kelly, my co-worker. She is a lot of fun and really helping me to learn the catering and party planning ropes. This was Friday's event at The Ashton Depot. We hosted a luncheon for 500 and I couldn't help but think that I really really like this job. Who can beat a job where you are surrounded by good food, fun people, and parties galore?
Monday, October 16, 2006
Today is World Food Day, a time to focus on the issue of hunger in the world. I challenge you to see how much you really know about it. Take this quiz published by the BBC.
Tuesday, September 19, 2006
So this morning I called my niece to wish her a happy birthday before school and I got some other news too...My sister is having another baby! Madison turned 9 today and the twins Matthew and Mitchell are 7. Now they are adding a baby to the mix. This will be so fun!
The kids already asked if they could name it. Their suggestion? Magician. They wanna call it Magic for short. I'm sure they got that idea from some Disney movie or cartoon, but the irony of their suggestion makes me laugh. My sister and brother-in-law are in for a fun ride with a new baby and three little helpers! Let's just hope she doesn't take seriously their offers to help name it...
Monday, September 18, 2006
For my birthday this past weekend, my good friends Rebecca, Amy, and Callie organized a Girls' Weekend in honor of my 30th. Friday began with a great evening of pedicures, movies, girl talk, and baked Brie. Saturday was coffee and brunch (with more girl talk), Tea Time at Tempest in Dallas, and shopping at the Galleria. Could I have asked for a more girly weekend? I don't think so! I loved every minute.
Love those girls.
Love pedicures.
Love girl talk.
Love shopping.
And Love being 30.
Friday, September 15, 2006
Yeah, that's right people I am turning 30 tomorrow! Lots of people have asked me how I feel about it. Honestly? I feel great! My roommate said yesterday that now I am officially thirty, flirty, and thriving.
I can live with that!
Downtown – things'll be great when you're
Downtown – no finer place for sure
Downtown – everything's waiting for you
So, now I am officially employed Downtown. The lyrics from this Petula Clark song may be a bit ambitious (I'm not sure everything is waiting for me there…), but the tune seemed appropriate to usher in this new chapter of working in downtown Fort Worth.
I just started working for the hospitality management company that manages The Ashton Hotel and The Ashton Depot in Fort Worth. They brought me on board to help coordinate people, events, and general business stuff. I have a lot to learn about the hospitality business, but those of you who know me well know that I love to take care of people. This is a great opportunity to do something professionally that I have always enjoyed doing at home! I am working with a great team including managers, executive chefs, event planners, and more. I can't wait to watch and learn.
And, for those of you in the Fort Worth area, these are gorgeous venues for weddings, receptions, parties and more. You can expect luxury treatment and a unique Fort Worth flair. Very chic!
Monday, September 11, 2006
Me too.
On 9/11, I was living in Turkey. I remember that it was about 3:00 p.m. and I was walking down a busy Istanbul street on my way to a popular shopping area with my friend Elizabeth. There wasn't anything out of the ordinary that day, other than the "normal" of everyday life overseas…constantly speaking and thinking in a foreign language, practicing care to not look men in the eyes (important in a Muslim culture), and smiling at the beggar children who always followed us down city streets asking for money.
My cell phone rang and an American friend who also lived in Istanbul said, "Hey there's something going on in New York. I'm watching CNN and it looks like the whole city is on fire." "Okay, Clay," I said. "Thanks for calling." Then I hung up and was actually annoyed that he would interrupt my path to the mall with news of a fire thousands of miles away in New York. Within fifteen minutes, he called again and said, "Nicole, as soon as you guys get to the mall, you need to find a department store with a television. You won't believe it. There's been a terrorist attack in New York and this is big."
We sped up our pace to the mall and immediately went to the electronics department of the biggest store we could find. Without asking, we switched the channel from a Turkish soap opera to CNN in English. Then we saw the pictures of the towers – both smoking by this point. I stood about a foot from the TV in disbelief and I remember thinking that my mouth simply wouldn't close. It felt frozen in shock. Within minutes, the Turks standing around us took notice of what was happening on the screen. This was the first they had seen of the news, and a crowd gathered around the television. They began to say in Turkish, "Change it to Turkish! I can't understand English!" So they switched the channel and the reporting was now by a Turkish reporter, displaying the same images we'd just seen of the towers.
My cell phone rang again and I heard my mom's voice. I couldn't help but break down and cry. "Mom, what's happening?" "Are you okay? Where are you? What are you doing?" She asked a million questions and I remember saying to her, "Mom, you're in America, not me. Nothing is happening here. It's happening there!" I remember her saying at the end of our conversation "The day is not over yet." Then it hit me that it was early morning in the U.S. and she was right. Who knew what the rest of the day held?
The next few days we (me, Elizabeth, and other Americans living in the city) were sort of in a holding pattern. I remember our company issuing plans with all kinds of scenarios and emergency plans to evacuate if that was necessary. We sat glued to CNN all day for three days.
Things I remember most about those days:
1. I felt helpless.
2. I cried a lot.
3. I didn't want to go back to work when things began to settle down.
4. I wanted my mom.
5. I prayed non-stop for the families who had lost people they loved.
I also remember my Turkish neighbors and friends who expressed so much concern for Americans and sadness at such a cowardly act of terrorism. They really were sympathetic. One neighbor even broke down in tears when she was telling me how sorry she was for our loss. Turkish people (and much of the rest of the world) understand the effects of terrorism. They have lived with it as long as they can remember and stand alongside anyone else who is affected by its devastation. I also remember many of them saying "This is NOT the way of Islam." They were heartbroken that now Islam had been the basis for such an act of terrorism.
It's been a long five years. This is not the place to comment on the state of things now. But it is a place to share a story and hope that many others, on this day, will remember that our world is broken. It is in need of redemption. My faith in Jesus Christ tells me the kind of redemption that's needed can only come through Him. If anyone does, He understands betrayal, pain, surrender, and ultimate victory over evil. In Him, there is goodness, hope, healing, and salvation for all people on earth. May we be reminded of those things today…
Rarely do I use this blog for entries like these because it seems like more of personal journal entry than something to be public. But, in this case, it is part of me seeking to identify with other people's experiences on that day and offer a word of hope, even on a day that is very solemn for many Americans.
Saturday, September 02, 2006
Hey, for all of you who are concerned about global issues, I totally recommend Jeffrey Sach's The End of Poverty. This book has completely upset my mind over the past few months and helped me understand more about the issue of extreme poverty in the world. Now, many nay-sayers saw this book when I was reading it and commented "the end of poverty - yeah, right!", or "hmmm. the end of poverty. that sounds like Bono's favorite book", or _____ you fill in the blank on things people might say when they don't understand the issue. Or better yet, when they want to ignore it.
I was introduced to the book when one of my students gave it to me as a gift. He bought it in Delhi and was very thoughtful to bring it back from his study abroad assignment. Until I visited India last year I had never really given much thought to the serious issue of poverty and how it affects global politics, health, education, and culture. Sachs has writen a great book for the average Westerner who doesn't know that much about how we as a developed society either help or hurt the poor of the world.
I won't be so bold to say that now I understand everything about poverty, what causes it, or how to fix it. But this book really made me think. And every once in a while, shouldn't we be reading something that makes us think?? It's a good read. Check it and let me know what you think...
Wednesday, August 30, 2006
1. The sun is out and it's less than 90 degrees. This is a major bonus for Texas in August.
2. I'm having lunch with my grandparents...I'm glad they are only 20 minutes away.
3. My birthday is in 17 days.
4. I have a job interview tomorrow.
5. I went running this morning by the river.
6. My birthday is in 17 days.
7. I watched a funny indie film some friends made recently. Check it out if you're into that kind of thing: http://www.jmcvideo.com/movies/recipe.wmv
8. I decided to go to Oklahoma this weekend. Yeah...I know...but it was cheaper than Cancun for Labor Day.
9. My birthday is in 17 days.
10. I am cooking dinner for friends - one of my favorite evening activities.
Did I mention that my birthday is coming up? Just making sure you caught that...
Monday, August 28, 2006
Probably most tourists don't take photos in the cemetery, but this cross was just too gothic and German to pass up...
Friday, August 25, 2006
Long Overdue:
Berlin Pics
So, finally. I am going to post some pictures of my trip to Germany in July. The trip was the overseas portion of my final project at CBU - an amazing opportunity to take 25 high school students and six incredible college student leaders on a two-week ministry project. Here are some of the pictures. Enjoy!
This is a portion of what's left of the Berlin wall, now called the East Side Gallery. Artists from all over world had a hand in decorating this mile stretch of this historic cement.
This is our leadership team (the six incredible college student leaders) that made sure all 25 high school students were taken care of in Berlin.
This is the door of the Castle Church, where Martin Luther nailed the 95 theses in Wittenburg, Germany.
This is the inside of the Castle Church.
Wednesday, August 02, 2006
2 plane rides
7 fuel stops
12 sweet truck stop bathrooms
1350 miles
24 hours of u-hauling
getting Nicole back to Texas = priceless
I'll update more later with some great pictures of Germany...
Thursday, July 27, 2006
I want to share with you a few things I've learned during my extended stay...
1. There's nothing like taking a walk on the beach - it's absolutely free, relaxing, and always worth the drive.
2. "Sunny California" is your nickname because you've earned it.
3. One can never have too many swimsuits.
4. Flip flops actually do go with everything.
5. There is such a thing as going too slowly on the freeway...it's called 80 mph.
6. Big sunglasses are not just "in", they are necessary.
7. In n' Out burgers and shakes are seriously worth every stinkin' calorie and fat gram.
8. Getting stuck in traffic can actually be a very productive time thanks to rollover minutes.
9. Your greatest strengths are your cultural diversity, open-mindedness, and casual approach to life. Careful, though, because they can also be your worst enemies.
10. The car trunk essentials: beach chairs, bottled water, and a beach towel. Just in case.
Thanks for letting me stay. I enjoyed it immensely and hope one day I'll return and continue to learn more about what a wonderful place you are. You and your residents have been amazing hosts to me this past two years. I am truly grateful...
Wednesday, July 26, 2006
Last night's goodbye party.
So, last night some good friends hosted a goodbye party for me at their home. It was a great time to see lots of people before I leave on Friday...I was truly blessed by seeing many students, fellow staff, and friends from my time here at CBU. My favorite part of the party was when my friends presented me with a bible that had been highlighted and written in by each person at the party. It was very special to see which portions of scripture stood out to friends as they send me off to begin a new chapter in Texas. I was truly honored. I will definitely miss the CBU family and count it a true blessing to have been a part of this community for the past two years.
Now there's only 36 hours till my brother and I begin the long trek to Texas in the U-Haul!
Thursday, July 13, 2006
So, just a short update...I arrived in Berlin a couple of days ago with a group of 30 students. We spent a full 5 days in training at CBU and left directly from there for Berlin (hence, the inability to update...) So far our time here has been amazing. We are now experts at the U-bon and Berlin streets. It has been fun to explore the city together and to see the excitement of all of these students. For most of them this is the first time they have ever travelled overseas and it is great fun to be the one leading them in this experience.
I'm moving to Texas!
So I guess this makes for two somewhat big announcements in one entry. Whoa. Yeah, I know for those of you faithful readers (all four or so) this is like a major event. Anyways, after much thought and prayer over the past several months it is clear that I am heading back to Texas. I will miss California and working with students at CBU, but I am honestly looking forward to the opportunity to be near friends and family again. If there is one thing I could change about my life in Cali, it has been that I wish I could have transported all my friends with me when I moved two years ago! Overall, though, it just seems like it's time to go. And I am excited about the change. I'll keep you posted on the details but it looks like I'll be in Fort Worth by August...just in time for the blazing heat, my nephews' birthday, and maybe even the ACL music fest in September. Can't wait.
Sunday, July 09, 2006
Check out my nephew Matthew staring in a Make-A-Wish video. This commercial is playing in selected markets in West Texas...check him out!
Tuesday, June 27, 2006
Associated Press
Tuesday, June 27, 2006
(source: Fox News)
CORPUS CHRISTI, Texas — A Corpus Christi woman says she got something horrifying in the mail.
Corpus Christi police say the woman reports her ex-boyfriend mailed her a severed human finger.
Police haven't released the identities.
Police Captain John Houston says police aren't sure which finger was removed or how it was removed, but that the finger appeared to have been cleanly severed and washed.
Police said a letter was enclosed, stating -- quote -- "This is the last chance to touch you."
The 32-year-old woman filed for an emergency protective order from the 34-year-old man last week before receiving the package. Police say the man moved to the Houston suburb of Spring last week and hasn't been located.
Yeah, so I think that's how you know. I guess maybe some would call him a romantic...I mean, I guess he didn't do half bad with the note. But seriously, I'd call it psycho. Remind me to never date a guy missing a finger...
Monday, June 05, 2006
This time of year always makes me think of my summers in Turkey. Oh, how I miss the busy streets of Istanbul, the late night dinners on my neighbor's balcony, and the fruit stands on the way home. It seems like every summer I know someone who gets to travel there (either from CBU or other connections) and I must confess that I am jealous.
This is one of my all time favorite views of the ancient city from the top of Galata tower. A friend snapped it last summer while I was pointing out all the highlights of the city to my friend Deb. (by the way, those are her hands seemingly sprouting out of my profile in this photo)
Friends who are there now:
You simply must go to Galata and see this view for yourself. 360 degrees of pure Istanbul!
Others who have been there:
Remember how fabulous this city and the people are?
The rest of you who haven't been to Turkey:
See what you are missing. Why have you not ventured into this historical Mediterranean heaven?
Wednesday, May 31, 2006
Monday, May 22, 2006
So, my best friend from college, Shawn, is here and we are enjoying the time to hang out. We went to see this hilarious musical on Saturday night in LA called Internet Dating: The Musical. It was a whole spoof on the internet love/dating operation with some really great song-writing.
YOU ARE CUTE BUT YOU CAN'T SPELL. For those who rationalize that maybe Mr. or Miss Right is really smart and great, they just have a hard time using spell check...
DID YOU READ MY PROFILE? So appropriately asking the question that often comes up when people ask questions that are already covered in that little profile you wrote about yourself. Why the heck are you asking me if I am a Hindu? Didn't you read my profile that clearly says I follow Jesus and am looking for someone who thinks the same way...? No, I'm not into astrology or supporing gay marriage. Geez.
CHECK MY INBOX. A hysterical song about how many times a day we check our inboxes...before coffee...after coffee...between making copies at the office...before lunch...after lunch...immediately upon returning from the restroom...you know the drill...
INTERNET DATING IS THE BEST THING EVER. For the days when it seems like a good idea.
I NEVER UNDERSTOOD WHY YOU WERE SINGLE. I think in its own sort of way this is meant to be uplifting coming from friends, but let's be honest it really is not a compliment. I'd rather someone say how cool it is that I get to travel the world, keep up with fashion trends, or spend four hours trying on shoes. That brings out the positive aspects of living the cosmopolitan life of a young single woman.
INTERNET DATING IS THE WORST THING EVER. For those days when reality hits and you think about how ridiculous it really is to be writing a profile promoting yourself hoping some guy will ask you out on a date based on what you've written.
When you think about it, it's a really bizarre way to meet people. Honestly I prefer the guys who talk to me in the grocery store or help me out on the paint aisle at Home Depot. At least I know that they have some guts and are willing to take a stab at talking to someone in person. I dig guys with guts..because let's face it, some really wimpy guys can write ANYTHING in their profile. But you can't fool me into thinking that you work out six times a week and are a professional body builder if your grocery cart is full of Twinkies and beer. Not to mention the fact that you are carrying around an extra 30 lbs - and I don't mean the super size bag of dog food in your cart...
Ah, the beauty of seeing people (and internet dating gurus) for who they really are! And, the appreciation for people who can write really funny songs about it.
If you're in LA in the next couple of weeks, I totally suggest you check out Internet Dating: The Musical at the art/works theater. It's playing until June 4.
Friday, May 12, 2006
Thursday, May 11, 2006
Anyways, Jenni McCarthy was the guest on the show...appropriately referred to as "Miss Nasty" by Carson during the interview. The STOMP performers were phenomenal and it was fun to see them and all of their percussion tools up close. I never thought I'd see the day when I referred to banging on metal trash can lids as music, but hey, it works for STOMP. The best part of the evening was before Last Call we were waiting outside of the NBC studio. Ellen Degeneres drove by and waved at us...and I am sure she was waving directly to me behind that dark SUV tinted glass from the backseat. I'm sure of it. Then, while she was filming her "ellen in the park" shows to be aired next week, we watched Kanye West perform Golddigger (or is it Golddigga?) on stage followed by a duet with his mom. It was a good night to be in Hollywood...
Oh, and the show will actually air on May 17. So, if you are into staying up till late to watch it, maybe you'll catch a glimpse of me. Maybe. I should be easy to spot - the normal size person on the front row who looks like they have eaten a brownie sundae or two...
Tuesday, May 09, 2006
Last Call with Carson Daly - Watch it on Wednesday night if you are one of those people who can make it until after Conan O'Brien (the really really late night tv). I'll be in the studio audience probably providing fake laughter and loud clapping when prompted. I'm following up the studio audience gig with the STOMP performance at Pantages. Okay, so I'm not in the STOMP performance, but I'll be there to watch it. Hooray for Hollywood nightlife!
Friday, May 05, 2006
Caution: Big Turns Ahead
So, it looks like I'll be taking a few turns in the coming months...
For the past year or so, I have really wondered if this is it for me. This being serving as a faculty member at a great Christian university in Southern California. I have loved several aspects of this job. I have loved the fact that every day I get to influence students to think beyond themselves and look towards a world in need of Christ. I have loved walking alongside so many college girls and advising them about issues like accessories and boys and everything in between. (Of course, always coupled with my honest confession that I don't know it all, I'm just happy to listen and talk about it.) I have loved being in an environment with colleagues who are always full of thoughtful conversations and new ideas about how to teach and challenge students. But, even with all of these things I've loved...
I've discovered that I don't quite fit in academia. I'd much rather be out there doing what I'm challenging my students to do. Everyday I stand in front of them and say "Go out from here and take the gospel with you wherever you go - in business, into the classroom, into the arts & music - into the WORLD. Jesus is way too valuable to be relegated to Sundays mornings, so be Christians that actually live like them. When you do, the world will notice." Having this as my driving theme for the past two years was bound to get to me at some point. Now, I get to step out and seize the opportunity to use my skills and education in the working world. Serving at CBU has been a tremendous opportunity for me, and I am truly grateful for the time I've spent here. But it's clear the time has come for me to move on...
Move on to what, you ask? Well, that's a good question...one I'm not quite sure I know how to answer yet. All I know at this point is that I am searching out various job opportunities. Texas, NYC, Washington DC - they've all been on the table. So, I am starting the job search and praying like crazy God will direct me to the right place. I know He will. He has proven Himself faithful too many times for me not to trust Him.
I am really glad this path is full of curves. I wouldn't do well on the straight, cruise-controlled, predictable, and adventure-less road...that path lacks excitement and speed. Just check with anyone who knows me well, and they'll tell you that I've got the driving record to prove it.
Friday, April 28, 2006
If you'd like to get involved in expressing your concern for the worst humanitarian crisis in our day, please visit: http://www.savedarfur.org/
People all around the world: Stand together against the genocide in Darfur. Take some responsibility in bringing hope and relief to an entire generation of people...before it's too late.
(photo courtesy of Human Rights Watch - www.hrw.org)
Sunday, April 16, 2006
Is it California...or Europe?
I must have asked this question four hundred times during my three-day road trip to Central California this week. The drive up the 101 to Morro Bay was absolutely breathtaking. Spring has made everything green and painted every spare patch of grass with wildflowers. My friend Merea and I had a great time on the scenic drive up and enjoyed the chance to explore several of Central California's (aka The Wine Country) attractions. We visited Hearst Castle, which many of you may recognize as the most extravagant residence in all of North America. It was built by W.R. Hearst - a journalism tycoon in 1930's & 40's - and the first ever licensed female architect, Julia Morgan. It is a fascinating story of a man and his dream home and the woman who built it for him...and, oh, what a place! You'll probably recognize his pool that shows itself in movies from time to time.
As we drove along the coast, we stopped a several piers just to walk out and take a deep breath of ocean air. I can hardly look at the ocean without thinking of Habakkuk 2:14 "for the earth will be filled with the knowledge of the glory of the Lord as the waters cover the sea". What an amazing picture of His depth that simply cannot be measured or matched!
Venturing inland revealed countless wineries all bragging the best California wine and offering free tastings. Don't worry, Mom (and other Baptist friends), we didn't give into the temptation to visit all of them.... We did NOT heed the advice of the couple sitting next to us at breakfast in our hotel. Their advice? "Oh, you should visit all of them! There are only like 22 or so in that area and you get seven free tastes at each one. (*note: a taste is more like half a glass*) Yesterday we hit eight or so and came home with who knows how many bottles." My question to them? How the heck did you make it back here for breakfast?!?!
Two four-eyed girls! I think Sofia looks a little more like a Hollywood baby than a Chicago one. What do you think?
Thursday, April 13, 2006
what a place! Marshall Field's, pizza, city streets, Wicked, wind, Sears Tower, the El, the Magnificent Mile, Lincoln Park, and so much more! That city truly has so much to offer. I enjoyed wandering the city streets and listening to the constant hum of the El train. I won't even try to guess just how many hours I spent in Marshall Field's...It would probably compare to the number of times I exclaimed to Sofia, "you are so cute!" She responded with a smile every time...
Thursday, April 06, 2006
Check out this website and learn more about the indie film INVISIBLE CHILDREN. Watch the trailer. I'm certain you'll be moved to (at the very least) think about how you can get involved. This film is having an catalytic effect on college campuses all over the USA. I'm amazed at how serious this generation takes issues like these. On one hand, it seems like they are all born with ipods and cell phones in their spoiled little hands. On the polar opposite hand, they are deeply moved by global issues....Christians and non-Christians alike. They are exposed to more information than any other generation, and don't ignore it. They see the emptiness of words without action, and I've observed them to be passionate about global issues and for the believer, how it connects to being a follower of Christ. They have taught me a great deal about the kind of passion it requires to make a difference in the world. It's the kind of passion that involves a willingness to suffer. A willingness to give up their small ambitions of the American dream, and trade it for something eternally valuable. That kind of passion can only be fueled by One who suffered and paid the price we could never pay. He suffered, died, and defeated death to remedy situations like what's happening in Uganda right now (...and Darfur, Iraq, Vietnam, and countless other places...) Take a minute to learn about INVISIBLE CHILDREN and consider it a challenge from this generation to take seriously the desire of Jesus to bring hope and restoration to all the earth...
Monday, April 03, 2006
check out this story reported on Foxnews today:
Okay, this is just plain sad. The situation? Kids in America are too fat to fit in the standard size car seat, so now manufacturers are creating the "Husky" seat to accomodate them. They added 4 inches in the seat (to accomodate larger bottoms) and made room for 10 extra pounds per kid. Are you serious, people??? Has anyone ever thought of limiting their kids' intake of fries and chicken nuggets instead of redefining car seat engineering? This is just plain ridiculous...! Now, I'm not a mom and don't plan to be anytime soon, but God help me if I have to buy my kid a Husky. That'll be my cue to quit feeding my kid junk and get them on a plan to lose that extra 4 inches - in a hurry!
(*please note: this kid in the photo has no relation to this story except that he's the kid who came up when I googled "fat kid photos". Hope he's not offended...*)
Friday, March 31, 2006
Looking forward to Chicago.
So, one week from today, I'll be on my way to Chicago to see my good friends Keri, Kevin, & Sofia Sheckler. Keri and I served overseas together in Turkey and have a wealth of shared experiences. She was the one who showed me the ropes overseas and I'll always be grateful for her adventurous approach to living in another culture. She was always the one to ask the question "Why not?" in relation to all things cultural and adventurous. I love that about her! Kerr and I also have a shared love of the theater. Les Miserables in London and now we are adding Wicked on Broadway in Chicago to our list of theater excursions. I'm starting the book this weekend in preparation for the theater experience. It's rare that I actually get to read something for fun (and not for teaching) so I'm looking forward to that too...hopefully the clouds and the rain hang around to make for good Saturday reading time.
Hmm...what else? Spring Break is just around the corner and it's obvious my students' minds have already turned to mush. They are there in the flesh but simply absent in the mind. I can't blame them, I guess. I was there fairly recently. I remember the frantic thoughts just before the end of the semester and the lack of sleep I suffered from my plain old procrastination. Oh, I am so glad those 10-15 page research paper days are over! My roommate from grad school can testify that I never really felt like the academic type and often wondered, "What the heck am I doing here?"...which makes me wonder why in the world God has chosen to place me back into academics...but that seems like another blog entry entirely. He definitely has a way of placing us where He wishes and doesn't always expain why. I guess that's why He's God and we are not. He defines us and we don't define Him. Believing that allows me to trust His infinite wisdom and be continually reminded that if I was in control, this would be a very scary journey indeed. I'm grateful that He sees the big picture and I don't. Otherwise, I fear I would be obsessive about how to move to what's next, instead of trusting Him to hold my future and patiently guide me on the journey...
Friday, March 24, 2006
A confession: I wanted to be New York, so I took that "what American city are you?" quiz twice to rig it. What can I say? I wanted to be labeled as cosmopolitan and sophisticated. =) Besides, any of you who know me know that I am far from competitive - just ask my family and they'll tell you I'm a middle child peacemaker all the way. I even refuse to play board games with them simply because someone always looses! I can accept the cosmopolitan and sophisticated bit, though, even if I did cheat a little.
Wednesday, March 22, 2006
|You Are New York
Famous people from New York: Sarah Michelle Gellar, Tupac Shakur, Woody Allen
Monday, March 13, 2006
So, yeah, The Bachelor and his reality TV girlfriend pick are done. Geez, maybe reality TV is real once in a while. I mean, what human being on the planet can keep up with an all-romance-no-real-grit-or-commitment-required relationship and expect it to turn into love?
Sorry, Sarah. Hopefully you and Trav can move on from your non-reality romance into something that resembles real life. The kind of real life where people don't have their first date on the French Riviera or Venice...
Sunday, March 12, 2006
Amy in Cali
This past week, my friend Amy Nobles was in California. Amy is a dear friend and it was refreshing (to say the least) to get to spend some time with her. She is a great listener and a great encourager - just one of those people you LOVE to be around. She also loves to laugh, so her presence was a much needed breath of fresh air to my life in California!
Amy is a worship leader and has a brand new cd out. To listen to one of her great new songs "Lord I Praise You", go to http://myspace.com/amynobles
To buy the cd (which I'm certain you'll want to do after listening to a clip), visit her website:
Beyond the Edge
As many of you know, I am working at California Baptist University. I have several different responsibilities at the school, but there is one I am particularly excited about: Beyond the Edge. Beyond the Edge is a brand new high school missions experience we began this year at CBU. Basically, we have invited 30 high school students to go on a 3-week mission trip to Germany this summer. The students will spend an entire week in intensive training on campus, and then we will depart for two weeks of service in Berlin. It is so exciting to be a part of developing this program. It has long been the desire of CBU to encourage and equip young people to serve God all over the world, and Beyond the Edge is part of that.
I have a team of six CBU student leaders (pictured) and we are all working together to make this a meaningful experience for these high school students. We are excited to see how God will use these 3 weeks this summer in the process of discipleship, growth, and maturity for these students. We are also praying for how He will use us to serve Him in Germany this summer. Our desire is to see Christ lifted up before all people as the only One who is able to offer new life. May He use us to proclaim that truth!
Overdue: An update on NASCAR
Okay, so I liked NASCAR! It was more exciting than any other sporting event I've been to. The vibration of the fast car noise and the excitement of 100,000 people packed in grandstands was exhilarating! At first, I wondered if it would really be fun watching these cars go in the same circle for 250 laps, but it was actually really cool.
Perhaps the most fun was watching the die hard fans in their multicolored caps, halter tops, and jackets - each one supporting their driver. It seemed like almost a religious experience for some of them..."C'mon Tony, don't let me down! ...Jeff Gordon, I'm here for you, man!...This is the best day of my life because Matt won..." Hmm...I'm thinking that many of them could benefit from something a little more substantial for a life motivation, because after all, NASCAR is bound to let you down someday...There will come a day when the keg's empty, the cars are all burnt out, and the multicolored jackets no longer fit...
Tuesday, February 28, 2006
I admit it. I am a closet fan of The Bachelor. Tonight my roommate Kimberly and I watched the season finale and we are celebrating Travis' pick of Sarah. She was undeniably the most poised, honest, and beautiful (outside and in) woman on the show. Way to go, Trav! I know, I know, you probably pity me at this point because I have no other exciting stuff to blog about... c'mon, Nicole, get a life! But, humor me please. And allow all those other closet fans to revel in the excitement of a "nice girl" victory. Hurray for all the nice girls out there! It's fleeting, but isn't reality/fantasy love fun...?
Sunday, February 26, 2006
Friday, February 24, 2006
So, this weekend I am in for a cultural experience. Usually this time of year, I would be trotting off to Europe or Asia for some sort of work trip. But this Spring I'm up for a whole new cultural experience: NASCAR. My brother Jeff (probably one of the funniest people I know) is coming to visit me this weekend so we can go to the race at Fontana. I am pumped! I don't know that much about the sport, but I've been studying in preparation for Sunday's race. I know what pole position is. I know that we need earplugs and binoculars. And I know not to carry my big purse ("you don't want to be keeping up with a bunch of crap in a crowd of 80,000 people" - an actual quote from Jeff). So, I'm all set! I mean, what else is there to know?
I'm really looking forward to hanging out with Jeff. Little brothers, even if they are 27-year-old grad students, have the ability to make you laugh about pretty much anything, don't they? Whether it is the noise the squirting ketchup bottle makes or the shared family jokes, I'm certain it will be a laughable time. Plus, I kinda appreciate a date who's willing to honestly tell me not to bring my purse loaded down with "crap" to our day of fun. That's kinda cool...other men could learn from that kind of transparency!
Yay for the NASCAR cultural experience! I'll keep you posted!

subset: commoncrawl


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Carnitine fumarate
100 mg
Other Ingredients: Purified water, natural flavors, stevia extract (steviol glycosides), potassium sorbate.
Does Not Contain: Milk, eggs, fish, shellfish, tree nuts, peanuts, wheat, soy.
Warning: Keep out of the reach of children. If pregnant or nursing, please consult your healthcare practitioner.
Storage: Refrigerate for best taste. Use within 45 days of opening.
‡Proprietary Liposomal Delivery System utilizing a specialized phosphatidylcholine complex with a unique ratio of PC, PE and oleic acid.


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- Snug trunk fit
- Two different fabrics to help you feel great in all the right places.
- Matching drawstring to help make this fit accordingly to your needs.
- Front lining to hold everything in place.
Material:80% Nylon 20% Elastane