DE68904018T2 - Antihypercholesterolemische 4,5-diaryl-2-substituierte thioimidazole. - Google Patents
Antihypercholesterolemische 4,5-diaryl-2-substituierte thioimidazole.Info
- Publication number
- DE68904018T2 DE68904018T2 DE8989116858T DE68904018T DE68904018T2 DE 68904018 T2 DE68904018 T2 DE 68904018T2 DE 8989116858 T DE8989116858 T DE 8989116858T DE 68904018 T DE68904018 T DE 68904018T DE 68904018 T2 DE68904018 T2 DE 68904018T2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- carbon atoms
- pharmaceutically acceptable
- pharmaceutical composition
- effective amount
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
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- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005157 alkyl carboxy group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 239000003529 anticholesteremic agent Substances 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000003143 atherosclerotic effect Effects 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960002130 benzoin Drugs 0.000 description 1
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 238000001085 differential centrifugation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- RGWOAXNKJWTDFA-UHFFFAOYSA-N ethyl 11-bromoundecanoate Chemical compound CCOC(=O)CCCCCCCCCCBr RGWOAXNKJWTDFA-UHFFFAOYSA-N 0.000 description 1
- UBTQVPMVWAEGAC-UHFFFAOYSA-N ethyl 8-bromooctanoate Chemical compound CCOC(=O)CCCCCCCBr UBTQVPMVWAEGAC-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000019382 gum benzoic Nutrition 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 239000011539 homogenization buffer Substances 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 210000001853 liver microsome Anatomy 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 210000003470 mitochondria Anatomy 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229950005522 octimibate Drugs 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000002653 sulfanylmethyl group Chemical group [H]SC([H])([H])[*] 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000009424 thromboembolic effect Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 239000003656 tris buffered saline Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Chemical group 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/04—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D233/28—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/30—Oxygen or sulfur atoms
- C07D233/42—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/84—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Photoreceptors In Electrophotography (AREA)
- Dental Preparations (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/244,170 US4900744A (en) | 1988-09-14 | 1988-09-14 | Antihypercholesterolemic 4,5-diaryl-2-substituted thioimidazoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE68904018D1 DE68904018D1 (de) | 1993-02-04 |
| DE68904018T2 true DE68904018T2 (de) | 1993-04-29 |
Family
ID=22921646
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE8989116858T Expired - Fee Related DE68904018T2 (de) | 1988-09-14 | 1989-09-12 | Antihypercholesterolemische 4,5-diaryl-2-substituierte thioimidazole. |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4900744A (enExample) |
| EP (1) | EP0359197B1 (enExample) |
| JP (1) | JPH02174762A (enExample) |
| KR (1) | KR900004697A (enExample) |
| AT (1) | ATE83772T1 (enExample) |
| AU (1) | AU615572B2 (enExample) |
| DE (1) | DE68904018T2 (enExample) |
| DK (1) | DK451389A (enExample) |
| ES (1) | ES2053896T3 (enExample) |
| GR (1) | GR3006839T3 (enExample) |
| IL (1) | IL91620A0 (enExample) |
| NZ (1) | NZ230624A (enExample) |
| ZA (1) | ZA897022B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5290814A (en) * | 1988-11-21 | 1994-03-01 | Burroughs Wellcome Co. | Anti-atherosclerotic diaryl compounds |
| EP0505481A1 (en) * | 1989-12-12 | 1992-09-30 | Rhone-Poulenc Sante | 2-substituted 4,5-diphenyl-imidazoles |
| MX9203711A (es) * | 1990-01-12 | 1992-07-01 | Rhone Poulenc Rorer Sa | Derivados de imidazol y composiciones farmaceuticas que los contienen. |
| US5011851A (en) * | 1990-02-13 | 1991-04-30 | Bristol-Myers Squibb Co. | Imidazole carboxylic acids and esters and inhibition of blood platelet aggregation therewith |
| GB9019838D0 (en) * | 1990-09-11 | 1990-10-24 | Smith Kline French Lab | Compounds |
| US5179117A (en) * | 1991-12-20 | 1993-01-12 | Du Pont Merck Pharmaceutical Company | Antihypercholesterolemic 2-substituted imidazoles |
| US5310748A (en) * | 1992-05-11 | 1994-05-10 | The Du Pont Merck Pharmaceutical Company | Imidazoles for the treatment of atherosclerosis |
| US5364875A (en) * | 1992-05-11 | 1994-11-15 | The Du Pont Merck Pharmaceutical Company | Imidazoles linked to bicyclic heterocyclic groups for the treatment of atherosclerosis |
| WO1994008038A1 (en) | 1992-10-02 | 1994-04-14 | Trustees Of Dartmouth College | Bispecific reagents for redirected targeting of low density lipoprotein |
| US5491152A (en) * | 1994-03-23 | 1996-02-13 | The Du Pont Merck Pharmaceutical Company | Derivatives of cyclic ethers and sulfides for the treatment of atherosclerosis |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US465438A (en) * | 1891-12-15 | Alcide frangois trouard | ||
| US3636003A (en) * | 1969-11-17 | 1972-01-18 | Geigy Chem Corp | Substituted 2-mercaptoimidazole derivatives |
| DE2823197A1 (de) * | 1978-05-24 | 1979-11-29 | Schering Ag | Neue imidazolderivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| DE3228271A1 (de) * | 1982-07-29 | 1984-02-02 | A. Nattermann & Cie GmbH, 5000 Köln | Triphenylimidazolyloxyalkansaeuren und ihre derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| DE3323870A1 (de) * | 1983-07-02 | 1985-01-03 | A. Nattermann & Cie GmbH, 5000 Köln | Neue imidazol-2-ylthioalkansaeuren und ihre derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate |
| ZA854550B (en) * | 1984-06-18 | 1986-04-30 | Smithkline Beckman Corp | Leukotriene antagonists |
| US4743613A (en) * | 1986-04-08 | 1988-05-10 | Smithkline Beckman Corporation | Ester prodrugs of dopamine-β-hydroxylase, inhibitors, composition containing them, and method of using them to inhibit dopamine-β-hydroxylase activity |
| US4734421A (en) * | 1986-10-29 | 1988-03-29 | Merck & Co., Inc. | Anti-inflammatory substituted 2-benzyl-mercapto-imidazole and pyrimidine derivatives compositions and method of use therefor |
| US4935438A (en) * | 1987-12-29 | 1990-06-19 | Smithkline Beckman Corporation | Dopamine-β-hydroxylase inhibitors |
-
1988
- 1988-09-14 US US07/244,170 patent/US4900744A/en not_active Expired - Lifetime
-
1989
- 1989-09-12 EP EP89116858A patent/EP0359197B1/en not_active Expired - Lifetime
- 1989-09-12 KR KR1019890013199A patent/KR900004697A/ko not_active Withdrawn
- 1989-09-12 ES ES89116858T patent/ES2053896T3/es not_active Expired - Lifetime
- 1989-09-12 DE DE8989116858T patent/DE68904018T2/de not_active Expired - Fee Related
- 1989-09-12 AT AT89116858T patent/ATE83772T1/de active
- 1989-09-12 NZ NZ230624A patent/NZ230624A/en unknown
- 1989-09-13 DK DK451389A patent/DK451389A/da not_active Application Discontinuation
- 1989-09-13 IL IL91620A patent/IL91620A0/xx unknown
- 1989-09-14 AU AU41361/89A patent/AU615572B2/en not_active Ceased
- 1989-09-14 ZA ZA897022A patent/ZA897022B/xx unknown
- 1989-09-14 JP JP1237384A patent/JPH02174762A/ja active Pending
-
1993
- 1993-01-21 GR GR930400090T patent/GR3006839T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2053896T3 (es) | 1994-08-01 |
| DE68904018D1 (de) | 1993-02-04 |
| NZ230624A (en) | 1991-06-25 |
| EP0359197A1 (en) | 1990-03-21 |
| KR900004697A (ko) | 1990-04-12 |
| IL91620A0 (en) | 1990-04-29 |
| ATE83772T1 (de) | 1993-01-15 |
| EP0359197B1 (en) | 1992-12-23 |
| DK451389A (da) | 1990-03-15 |
| JPH02174762A (ja) | 1990-07-06 |
| DK451389D0 (da) | 1989-09-13 |
| US4900744A (en) | 1990-02-13 |
| GR3006839T3 (enExample) | 1993-06-30 |
| AU4136189A (en) | 1990-03-22 |
| ZA897022B (en) | 1991-05-29 |
| AU615572B2 (en) | 1991-10-03 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8339 | Ceased/non-payment of the annual fee |