ZA200200937B - Oxa- and thiazole derivatives useful as antidiabetic and antiobesity agents. - Google Patents
Oxa- and thiazole derivatives useful as antidiabetic and antiobesity agents. Download PDFInfo
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- ZA200200937B ZA200200937B ZA200200937A ZA200200937A ZA200200937B ZA 200200937 B ZA200200937 B ZA 200200937B ZA 200200937 A ZA200200937 A ZA 200200937A ZA 200200937 A ZA200200937 A ZA 200200937A ZA 200200937 B ZA200200937 B ZA 200200937B
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- 239000003472 antidiabetic agent Substances 0.000 title claims description 23
- 229940125708 antidiabetic agent Drugs 0.000 title claims description 19
- 239000000883 anti-obesity agent Substances 0.000 title claims description 6
- 229940125710 antiobesity agent Drugs 0.000 title claims description 6
- 230000003178 anti-diabetic effect Effects 0.000 title description 2
- 150000007979 thiazole derivatives Chemical class 0.000 title description 2
- 150000007978 oxazole derivatives Chemical class 0.000 title 1
- -1 alkylaryloxycarbonyl Chemical group 0.000 claims description 100
- 125000000217 alkyl group Chemical group 0.000 claims description 75
- 150000001875 compounds Chemical class 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 50
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
- 239000003112 inhibitor Substances 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 238000000034 method Methods 0.000 claims description 30
- 150000002148 esters Chemical class 0.000 claims description 29
- 239000000203 mixture Substances 0.000 claims description 29
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 239000003524 antilipemic agent Substances 0.000 claims description 23
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
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- 229940002612 prodrug Drugs 0.000 claims description 15
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- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 claims description 4
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- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- BAPROVDXKNPHAM-UHFFFAOYSA-N n-(2-aminoethyl)-3-(3,5-ditert-butyl-4-hydroxyphenyl)propanamide Chemical compound CC(C)(C)C1=CC(CCC(=O)NCCN)=CC(C(C)(C)C)=C1O BAPROVDXKNPHAM-UHFFFAOYSA-N 0.000 description 1
- WGESLFUSXZBFQF-UHFFFAOYSA-N n-methyl-n-prop-2-enylprop-2-en-1-amine Chemical class C=CCN(C)CC=C WGESLFUSXZBFQF-UHFFFAOYSA-N 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001979 organolithium group Chemical group 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- 230000002611 ovarian Effects 0.000 description 1
- BDOLXPFAFMNDOK-UHFFFAOYSA-N oxazaborolidine Chemical compound B1CCON1 BDOLXPFAFMNDOK-UHFFFAOYSA-N 0.000 description 1
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- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 229940083256 peripheral vasodilators nicotinic acid and derivative Drugs 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 229960003243 phenformin Drugs 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000008288 physiological mechanism Effects 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- RHGYHLPFVJEAOC-FFNUKLMVSA-L pitavastatin calcium Chemical compound [Ca+2].[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1.[O-]C(=O)C[C@H](O)C[C@H](O)\C=C\C1=C(C2CC2)N=C2C=CC=CC2=C1C1=CC=C(F)C=C1 RHGYHLPFVJEAOC-FFNUKLMVSA-L 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical group CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- LALFOYNTGMUKGG-BGRFNVSISA-L rosuvastatin calcium Chemical compound [Ca+2].CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O.CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O LALFOYNTGMUKGG-BGRFNVSISA-L 0.000 description 1
- IMNTVVOUWFPRSB-JWQCQUIFSA-N sch-48461 Chemical compound C1=CC(OC)=CC=C1[C@H]1N(C=2C=CC(OC)=CC=2)C(=O)[C@@H]1CCCC1=CC=CC=C1 IMNTVVOUWFPRSB-JWQCQUIFSA-N 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 150000003334 secondary amides Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 150000003557 thiazoles Chemical class 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 150000003577 thiophenes Chemical class 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- 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
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- 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
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Emergency Medicine (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15540099P | 1999-09-22 | 1999-09-22 |
Publications (1)
Publication Number | Publication Date |
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ZA200200937B true ZA200200937B (en) | 2003-07-30 |
Family
ID=22555274
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200200937A ZA200200937B (en) | 1999-09-22 | 2002-02-01 | Oxa- and thiazole derivatives useful as antidiabetic and antiobesity agents. |
Country Status (28)
Country | Link |
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US (1) | US7579479B2 (no) |
EP (1) | EP1218361B1 (no) |
JP (2) | JP4332315B2 (no) |
KR (1) | KR100682419B1 (no) |
CN (1) | CN1289490C (no) |
AR (1) | AR025756A1 (no) |
AT (1) | ATE420080T1 (no) |
AU (1) | AU782031B2 (no) |
BR (1) | BR0014189A (no) |
CA (1) | CA2388452C (no) |
CO (1) | CO5200832A1 (no) |
DE (1) | DE60041343D1 (no) |
EG (1) | EG24169A (no) |
ES (1) | ES2319097T3 (no) |
HK (1) | HK1049337B (no) |
HU (1) | HUP0204416A3 (no) |
IL (2) | IL147939A0 (no) |
MX (1) | MXPA02001847A (no) |
MY (1) | MY138525A (no) |
NO (1) | NO322500B1 (no) |
NZ (1) | NZ516820A (no) |
PE (1) | PE20010643A1 (no) |
PL (1) | PL364986A1 (no) |
RU (2) | RU2279427C2 (no) |
TR (1) | TR200200732T2 (no) |
TW (4) | TW200514783A (no) |
WO (1) | WO2001021602A1 (no) |
ZA (1) | ZA200200937B (no) |
Families Citing this family (87)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TW200514783A (en) * | 1999-09-22 | 2005-05-01 | Bristol Myers Squibb Co | Substituted acid derivatives useful as antiodiabetic and antiobesity agents and method |
AR030379A1 (es) * | 2000-08-22 | 2003-08-20 | Novartis Ag | Combinaciones |
AR033390A1 (es) * | 2000-08-22 | 2003-12-17 | Novartis Ag | Una composicion farmaceutica que comprende un antagonista del receptor at1 y un potenciador de la secrecion de insulina, el uso de dicha composicion para la fabricacion de un medicamento y un kit de partes |
US20060089389A1 (en) | 2000-08-22 | 2006-04-27 | Malcolm Allison | Combination |
EP1695716A2 (en) | 2000-12-26 | 2006-08-30 | Sankyo Company, Limited | Medicinal compositions containing diuretics and insulin sensitizers |
US7241785B2 (en) | 2001-03-23 | 2007-07-10 | Takeda Pharmaceutical Company Limited | Five-membered heterocyclic alkanoic acid derivative |
US7105556B2 (en) | 2001-05-30 | 2006-09-12 | Bristol-Myers Squibb Company | Conformationally constrained analogs useful as antidiabetic and antiobesity agents and method |
BRPI0211844B8 (pt) * | 2001-08-10 | 2021-05-25 | Nippon Chemiphar Co | composto de ácido fenóxi-acético ou um de seus sais farmaceuticamente aceitáveis, e, composição farmacêutica |
EP1442028A4 (en) * | 2001-11-06 | 2009-11-04 | Bristol Myers Squibb Co | SUBSTITUTED ACID DERIVATIVES, WHICH APPRECIATE AS ANTIDIBILICS AND AGENTS AGAINST OBESITAS, AND METHODS |
TW200300681A (en) | 2001-11-12 | 2003-06-16 | Ono Pharmaceutical Co | Carboxylic acid derivative compound and medicament containing same as active ingredient |
US7067517B2 (en) * | 2001-12-14 | 2006-06-27 | Nero Nordisk A/S | Use of compounds for decreasing activity of hormone-sensitive lipase |
EP1463751B1 (en) | 2001-12-21 | 2013-05-22 | Human Genome Sciences, Inc. | Albumin fusion proteins |
TW200305415A (en) * | 2002-03-22 | 2003-11-01 | Novartis Ag | Combination of organic compounds |
US6716842B2 (en) | 2002-04-05 | 2004-04-06 | Warner-Lambert Company, Llc | Antidiabetic agents |
US7057046B2 (en) | 2002-05-20 | 2006-06-06 | Bristol-Myers Squibb Company | Lactam glycogen phosphorylase inhibitors and method of use |
PL374860A1 (en) | 2002-07-09 | 2005-11-14 | Bristol-Myers Squibb Company | Substituted heterocyclic derivatives useful as antidiabetic and antiobesity agents and method |
KR101120337B1 (ko) * | 2002-07-09 | 2012-02-29 | 브리스톨-마이어스 스큅 컴퍼니 | 항당뇨제 및 항비만제로서 유용한 치환된 헤테로시클릭유도체 및 방법 |
AR041481A1 (es) | 2002-10-07 | 2005-05-18 | Hoffmann La Roche | Derivados de acido arilpropionico-oxazol y su uso como agonistas de ppar |
US7098235B2 (en) | 2002-11-14 | 2006-08-29 | Bristol-Myers Squibb Co. | Triglyceride and triglyceride-like prodrugs of glycogen phosphorylase inhibiting compounds |
US7148246B2 (en) | 2003-02-27 | 2006-12-12 | Sanofi-Aventis Deutschland Gmbh | Cycloalkyl derivatives having bioisosteric carboxylic acid groups, processes for their preparation and their use as pharmaceuticals |
DE10308353A1 (de) | 2003-02-27 | 2004-12-02 | Aventis Pharma Deutschland Gmbh | Diarylcycloalkylderivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
DE10308352A1 (de) | 2003-02-27 | 2004-09-09 | Aventis Pharma Deutschland Gmbh | Arylcycloalkylderivate mit verzweigten Seitenketten, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel |
DE10308351A1 (de) * | 2003-02-27 | 2004-11-25 | Aventis Pharma Deutschland Gmbh | 1,3-substituierte Cycloalkylderivate mit sauren, meist heterocyclischen Gruppen, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
DE10308355A1 (de) | 2003-02-27 | 2004-12-23 | Aventis Pharma Deutschland Gmbh | Aryl-cycloalkyl substituierte Alkansäurederivate, Verfahren zu ihrer Herstellung und ihre Anwendung als Arzneimittel |
DE10311984A1 (de) * | 2003-03-12 | 2004-09-23 | Freie Universität Berlin | Verwendung von NEP-assoziierten Molekülen zur Behandlung von nichtimmunogenen-nichthypertensiven Zivilisationskrankheiten |
BRPI0411412A (pt) * | 2003-06-13 | 2006-07-25 | S A L V A T Lab Sa | novas benzamidas como moduladores ppary |
WO2005000309A2 (en) * | 2003-06-27 | 2005-01-06 | Ionix Pharmaceuticals Limited | Chemical compounds |
WO2005049589A2 (en) * | 2003-10-14 | 2005-06-02 | Cadila Healthcare Limited | Heterocyclic compounds for the treatment of hyperlipidemia, diabetes, obesity and similar diseases |
SI1679074T1 (sl) | 2003-10-24 | 2011-04-29 | Santen Pharmaceutical Co Ltd | Terapevtsko sredstvo za keratokonjuktivno motnjo |
US7348329B2 (en) | 2003-10-29 | 2008-03-25 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for keratoconjunctival disorder |
CN1882327A (zh) | 2003-11-19 | 2006-12-20 | 症变治疗公司 | 含磷的新的拟甲状腺素药 |
EP1731513A4 (en) * | 2004-03-30 | 2007-10-31 | Daiichi Seiyaku Co | PHENOXYACETIC ACID DERIVATIVE AND MEDICAMENT CONTAINING THE SAME |
JP2007230868A (ja) * | 2004-03-30 | 2007-09-13 | Dai Ichi Seiyaku Co Ltd | 二環性化合物及びそれを用いた医薬 |
EP1586573B1 (en) | 2004-04-01 | 2007-02-07 | Sanofi-Aventis Deutschland GmbH | Oxadiazolones, processes for their preparation and their use as pharmaceuticals |
US7618981B2 (en) * | 2004-05-06 | 2009-11-17 | Cytokinetics, Inc. | Imidazopyridinyl-benzamide anti-cancer agents |
JP2008503482A (ja) | 2004-06-18 | 2008-02-07 | ワイス | 6−アルキル−5−アリールスルホニル−ジヒドロフェナントリジンの製造方法 |
KR100739367B1 (ko) * | 2004-07-14 | 2007-07-16 | 크리스탈지노믹스(주) | 설파마이드 유도체 및 이를 함유하는 지방대사 촉진용약학적 조성물 |
TW200608967A (en) | 2004-07-29 | 2006-03-16 | Sankyo Co | Pharmaceutical compositions containing with diabetic agent |
AR051446A1 (es) | 2004-09-23 | 2007-01-17 | Bristol Myers Squibb Co | Glucosidos de c-arilo como inhibidores selectivos de transportadores de glucosa (sglt2) |
US7635699B2 (en) | 2004-12-29 | 2009-12-22 | Bristol-Myers Squibb Company | Azolopyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
US7589088B2 (en) | 2004-12-29 | 2009-09-15 | Bristol-Myers Squibb Company | Pyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
EP2527337A1 (en) | 2005-04-14 | 2012-11-28 | Bristol-Myers Squibb Company | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
WO2006117743A1 (en) * | 2005-05-03 | 2006-11-09 | Ranbaxy Laboratories Limited | Substituted aromatic compounds as antidiabetic agents |
US7521557B2 (en) | 2005-05-20 | 2009-04-21 | Bristol-Myers Squibb Company | Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods |
DE102005026762A1 (de) | 2005-06-09 | 2006-12-21 | Sanofi-Aventis Deutschland Gmbh | Azolopyridin-2-on-derivate als Inhibitoren von Lipasen und Phospholipasen |
US7488725B2 (en) | 2005-10-31 | 2009-02-10 | Bristol-Myers Squibb Co. | Pyrrolidinyl beta-amino amide-based inhibitors of dipeptidyl peptidase IV and methods |
FR2896159B1 (fr) | 2006-01-13 | 2008-09-12 | Merck Sante Soc Par Actions Si | Combinaison de derives de triazine et d'agents sensibilisateurs a l'insuline. |
FR2897536A1 (fr) * | 2006-02-17 | 2007-08-24 | Galderma Res & Dev | Utilisation du muraglitazar pour la preparation d'une composition pharmaceutique destinee au traitement des affections dermatologiques |
US7919598B2 (en) | 2006-06-28 | 2011-04-05 | Bristol-Myers Squibb Company | Crystal structures of SGLT2 inhibitors and processes for preparing same |
EP2046753A2 (en) | 2006-07-06 | 2009-04-15 | Brystol-Myers Squibb Company | Pyridone/hydroxypyridine 11-beta hydroxysteroid dehydrogenase type i inhibitors |
US7910747B2 (en) | 2006-07-06 | 2011-03-22 | Bristol-Myers Squibb Company | Phosphonate and phosphinate pyrazolylamide glucokinase activators |
US20080009534A1 (en) * | 2006-07-07 | 2008-01-10 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
US7795291B2 (en) * | 2006-07-07 | 2010-09-14 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as anti-atherosclerotic, anti-dyslipidemic, anti-diabetic and anti-obesity agents and method |
US7727978B2 (en) | 2006-08-24 | 2010-06-01 | Bristol-Myers Squibb Company | Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors |
US20100179131A1 (en) | 2006-09-07 | 2010-07-15 | Nycomed Gmbh | Combination treatment for diabetes mellitus |
KR100958831B1 (ko) * | 2006-09-19 | 2010-05-24 | 주식회사유한양행 | 헤테로아릴피리미딘 유도체, 이들의 제조방법, 및 이들을포함하는 조성물 |
CA2672956C (en) * | 2006-10-26 | 2015-02-10 | Amgen Inc. | Calcium receptor modulating agents |
AR065809A1 (es) | 2007-03-22 | 2009-07-01 | Bristol Myers Squibb Co | Formulaciones farmaceuticas que contienen un inhibidor sglt2 |
JP2010524953A (ja) | 2007-04-17 | 2010-07-22 | ブリストル−マイヤーズ スクイブ カンパニー | 縮合ヘテロ環11−β−ヒドロキシステロイドデヒドロゲナーゼI型阻害剤 |
PE20090696A1 (es) | 2007-04-20 | 2009-06-20 | Bristol Myers Squibb Co | Formas cristalinas de saxagliptina y procesos para preparar las mismas |
EP2152663B1 (en) | 2007-06-04 | 2014-03-19 | Ben Gurion University of the Negev Research and Development Authority | Tri-aryl compounds and compositions comprising the same |
JP2010529203A (ja) | 2007-06-11 | 2010-08-26 | ブリストル−マイヤーズ スクイブ カンパニー | 1,3−ジヒドロキシ置換フェニルアミドグルコキナーゼ活性化剤 |
JP5566288B2 (ja) * | 2008-05-30 | 2014-08-06 | 武田薬品工業株式会社 | 複素環化合物 |
WO2010004319A1 (en) * | 2008-07-07 | 2010-01-14 | Astrazeneca Ab | Combination comprising 6-flu0r0-n- ((1s, 4s) - 4- (6-fluoro-2, 4-di0x0-1- (4'- (piperazin-1- ylmethyl) biphenyl- 3-yl) -1, 2-dihydropyrido [2, 3-d] pyrimidin-3 (4h) - yl) cyclohexyl) imidazo [1,2-a] pyridine -2- carboxamide or a salt |
KR101036406B1 (ko) * | 2008-10-24 | 2011-05-24 | 박란 | 축구공 |
EP2196476A1 (en) | 2008-12-10 | 2010-06-16 | Novartis Ag | Antibody formulation |
WO2010093601A1 (en) | 2009-02-10 | 2010-08-19 | Metabasis Therapeutics, Inc. | Novel sulfonic acid-containing thyromimetics, and methods for their use |
PT2498758T (pt) | 2009-11-13 | 2018-10-23 | Astrazeneca Uk Ltd | Formulações de comprimido bicamada |
CA2780938A1 (en) | 2009-11-13 | 2011-05-19 | Bristol-Myers Squibb Company | Reduced mass metformin formulations |
PL2498759T3 (pl) | 2009-11-13 | 2019-03-29 | Astrazeneca Ab | Formulacje tabletek o natychmiastowym uwalnianiu |
TWI562775B (en) | 2010-03-02 | 2016-12-21 | Lexicon Pharmaceuticals Inc | Methods of using inhibitors of sodium-glucose cotransporters 1 and 2 |
WO2011130459A1 (en) | 2010-04-14 | 2011-10-20 | Bristol-Myers Squibb Company | Novel glucokinase activators and methods of using same |
WO2012031124A2 (en) | 2010-09-03 | 2012-03-08 | Bristol-Myers Squibb Company | Drug formulations using water soluble antioxidants |
TWI631963B (zh) | 2011-01-05 | 2018-08-11 | 雷西肯製藥股份有限公司 | 包含鈉-葡萄糖共同輸送體1與2之抑制劑的組合物與應用方法 |
EP2670397B1 (en) | 2011-02-01 | 2020-05-13 | Bristol-Myers Squibb Company | Pharmaceutical formulations including an amine compound |
DK2713722T3 (en) * | 2011-05-31 | 2017-07-03 | Celgene Int Ii Sarl | Newly known GLP-1 receptor stabilizers and modulators |
EP2574607A1 (en) | 2011-09-06 | 2013-04-03 | F. Hoffmann-La Roche AG | PDE10 modulators |
WO2014081660A1 (en) | 2012-11-20 | 2014-05-30 | Lexicon Pharmaceuticals, Inc. | Inhibitors of sodium glucose cotransporter 1 |
ES2864349T3 (es) | 2013-06-11 | 2021-10-13 | Receptos Llc | Nuevos moduladores del receptor GLP-1 |
CN103694195B (zh) * | 2013-09-18 | 2016-04-06 | 华东师范大学 | 芳香杂环类小分子有机化合物及衍生物、制备方法及医药用途 |
WO2015068156A1 (en) | 2013-11-05 | 2015-05-14 | Ben-Gurion University Of The Negev Research And Development Authority | Compounds for the treatment of diabetes and disease complications arising from same |
CA2969944A1 (en) | 2014-12-10 | 2016-06-16 | Celgene International Ii Sarl | Glp-1 receptor modulators |
WO2016161342A2 (en) | 2015-04-02 | 2016-10-06 | Threshold Pharmaceuticals, Inc. | Nitrobenzyl derivatives of anti-cancer agents |
WO2020068661A1 (en) | 2018-09-26 | 2020-04-02 | Lexicon Pharmaceuticals, Inc. | Crystalline forms of n-(1 -((2-(dimethylamino)ethyl)amino)-2-m ethyl-1 -oopropan-2-yl)-4-(4-(2-methyl-5- (2s,3r,4r,5s,6r)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2h-pyran-2-yl)benzyl) phenl)butanamide and methods of their synthesis |
CN114981251B (zh) * | 2020-01-21 | 2023-11-21 | 深圳信立泰药业股份有限公司 | 一种二苯并呋喃类衍生物组织蛋白酶k抑制剂及其制备方法和医药用途 |
JP7407651B2 (ja) | 2020-04-20 | 2024-01-04 | 東ソー・ファインケム株式会社 | 3-アセトキシスチレンの製造方法 |
WO2024100051A1 (en) | 2022-11-08 | 2024-05-16 | Genfit | Ppar-alpha/gamma agonist for use in the treatment of liver failure |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5036079A (en) * | 1989-12-07 | 1991-07-30 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
US5110812A (en) * | 1990-06-04 | 1992-05-05 | Bristol-Myers Squibb Co. | Azetidin-2-one derivatives as serine protease inhibitors |
US5175283A (en) * | 1990-06-04 | 1992-12-29 | Bristol-Myers Squibb Company | Azetidin-2-one derivatives as serine protease inhibitors |
US5250677A (en) * | 1990-06-04 | 1993-10-05 | Bristol-Myers Squibb Company | Azetidin-2-one derivatives as serine protease inhibitors |
US5037819A (en) * | 1990-06-04 | 1991-08-06 | Bristol-Myers Squibb Company | Azetidin-2-one derivatives as serine protease inhibitors |
JPH05213884A (ja) | 1991-06-14 | 1993-08-24 | Upjohn Co:The | 新規な4−アミノキノリン類およびこれを有効成分とする高血圧・鬱血性心不全の予防・治療剤 |
GB9113628D0 (en) | 1991-06-25 | 1991-08-14 | Ici Plc | Heterocyclic derivatives |
US5232945A (en) * | 1992-07-20 | 1993-08-03 | Pfizer Inc. | 3-aryl-2-hydroxypropionic acid derivatives and analogs as antihypertensives |
US5776983A (en) * | 1993-12-21 | 1998-07-07 | Bristol-Myers Squibb Company | Catecholamine surrogates useful as β3 agonists |
JPH08325263A (ja) | 1995-05-31 | 1996-12-10 | Sumitomo Metal Ind Ltd | 新規2−アミノ−3−フェニルプロピオン酸誘導体 |
AU712607B2 (en) | 1996-02-02 | 1999-11-11 | Merck & Co., Inc. | Method of treating diabetes and related disease states |
WO1997028149A1 (en) | 1996-02-02 | 1997-08-07 | Merck & Co., Inc. | Method for raising hdl cholesterol levels |
AU719146B2 (en) | 1996-02-02 | 2000-05-04 | Merck & Co., Inc. | Antidiabetic agents |
WO1997028137A1 (en) | 1996-02-02 | 1997-08-07 | Merck & Co., Inc. | Heterocyclic derivatives as antidiabetic and antiobesity agents |
GB9604242D0 (en) * | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
JP3215048B2 (ja) * | 1996-04-03 | 2001-10-02 | 日本たばこ産業株式会社 | プロピオン酸誘導体及びその用途 |
US5889025A (en) * | 1996-05-06 | 1999-03-30 | Reddy's Research Foundation | Antidiabetic compounds having hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
CA2259431A1 (en) | 1996-07-01 | 1998-01-08 | Eli Lilly And Company | Hypoglycemic and hypolipidemic compounds |
EP0925063A4 (en) | 1996-07-01 | 2000-12-27 | Lilly Co Eli | Blood-glucose-lowering and lipid-lowering compounds |
EP0948327B1 (en) | 1996-12-23 | 2006-03-08 | Merck & Co., Inc. | Antidiabetic agents |
WO1999007357A1 (fr) | 1997-08-08 | 1999-02-18 | Ono Pharmaceutical Co., Ltd. | REGULATEURS DE TYPE η DE RECEPTEUR ACTIVE D'AGENT DE PROLIFERATION DE PEROXYSOME |
AU8750298A (en) | 1997-08-28 | 1999-03-22 | Ono Pharmaceutical Co. Ltd. | Peroxisome proliferator-activated receptor controllers |
WO1999015520A1 (fr) | 1997-09-19 | 1999-04-01 | Ono Pharmaceutical Co., Ltd. | Composes de benzene fusionnes ou non fusionnes |
CN1302206A (zh) | 1997-10-17 | 2001-07-04 | 阿温蒂斯药物制品公司 | 喹啉衍生物的治疗用途 |
WO1999016758A1 (en) | 1997-10-27 | 1999-04-08 | Dr. Reddy's Research Foundation | Novel heterocyclic compounds and their use in medicine, process for their preparation and pharmaceutical compositions containing them |
JP4345230B2 (ja) * | 1998-03-10 | 2009-10-14 | 小野薬品工業株式会社 | カルボン酸誘導体およびその誘導体を有効成分として含有する薬剤 |
DE69828445D1 (de) | 1998-04-23 | 2005-02-03 | Reddys Lab Ltd Dr | Heterozyklische verbindungen,und deren verwendung in arzneimittel,verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammenstellungen |
GB9817118D0 (en) * | 1998-08-07 | 1998-10-07 | Glaxo Group Ltd | Pharmaceutical compounds |
ATE368037T1 (de) | 1999-04-28 | 2007-08-15 | Sanofi Aventis Deutschland | Di-aryl-säurederivate als ppar rezeptor liganden |
BR0010126A (pt) | 1999-04-28 | 2002-02-26 | Aventis Pharma Gmbh | Derivados de ácido tri-arìlico como ligandos receptores de ppar |
TW200514783A (en) * | 1999-09-22 | 2005-05-01 | Bristol Myers Squibb Co | Substituted acid derivatives useful as antiodiabetic and antiobesity agents and method |
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