SK9162000A3 - Integrin receptor antagonists - Google Patents

Integrin receptor antagonists Download PDF

Info

Publication number: SK9162000A3
Authority: SK; Slovakia
Prior art keywords: alkyl; aryl; oxo; compound; propyl
Prior art date: 1997-12-17

Application number

SK916-2000A

Other languages

English (en)

Slovak (sk)

Inventor

Mark E Duggan

Robert S Meissner

John H Hutchinson

Wasyl Halczenko

Ben C Askew

Paul J Coleman

Michael A Patane

Jiabing Wang

James J Perkins

Original Assignee

Merck & Co Inc

Priority date (The priority date 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 date listed.)

1997-12-17

Filing date

1998-12-14

Publication date

2001-03-12

1998-05-13 Priority claimed from GBGB9810182.7A external-priority patent/GB9810182D0/en

1998-05-20 Priority claimed from GBGB9810882.2A external-priority patent/GB9810882D0/en

1998-05-20 Priority claimed from GBGB9810892.1A external-priority patent/GB9810892D0/en

1998-05-26 Priority claimed from GBGB9811283.2A external-priority patent/GB9811283D0/en

1998-06-12 Priority claimed from GBGB9812686.5A external-priority patent/GB9812686D0/en

1998-10-13 Priority claimed from GBGB9822331.6A external-priority patent/GB9822331D0/en

1998-10-16 Priority claimed from GBGB9822701.0A external-priority patent/GB9822701D0/en

1998-12-14 Application filed by Merck & Co Inc filed Critical Merck & Co Inc

2001-03-12 Publication of SK9162000A3 publication Critical patent/SK9162000A3/sk

Links

229940127449 Integrin Receptor Antagonists Drugs 0.000 title abstract description 10
150000001875 compounds Chemical class 0.000 claims abstract description 410
125000003118 aryl group Chemical group 0.000 claims description 104
125000001424 substituent group Chemical group 0.000 claims description 59
125000004432 carbon atom Chemical group C* 0.000 claims description 27
125000005842 heteroatom Chemical group 0.000 claims description 22
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 19
229910052717 sulfur Inorganic materials 0.000 claims description 15
229910052757 nitrogen Inorganic materials 0.000 claims description 14
229910052760 oxygen Inorganic materials 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
125000006574 non-aromatic ring group Chemical group 0.000 claims description 10
208000006386 Bone Resorption Diseases 0.000 abstract description 32
230000024279 bone resorption Effects 0.000 abstract description 32
108010044426 integrins Proteins 0.000 abstract description 26
102000006495 integrins Human genes 0.000 abstract description 26
230000002401 inhibitory effect Effects 0.000 abstract description 25
208000001132 Osteoporosis Diseases 0.000 abstract description 20
230000033115 angiogenesis Effects 0.000 abstract description 20
201000010099 disease Diseases 0.000 abstract description 20
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 20
206010061218 Inflammation Diseases 0.000 abstract description 19
230000004054 inflammatory process Effects 0.000 abstract description 19
230000004614 tumor growth Effects 0.000 abstract description 19
206010012689 Diabetic retinopathy Diseases 0.000 abstract description 16
208000037803 restenosis Diseases 0.000 abstract description 15
206010027476 Metastases Diseases 0.000 abstract description 14
208000002780 macular degeneration Diseases 0.000 abstract description 14
230000009401 metastasis Effects 0.000 abstract description 14
201000001320 Atherosclerosis Diseases 0.000 abstract description 13
230000003612 virological effect Effects 0.000 abstract description 12
230000015572 biosynthetic process Effects 0.000 abstract description 10
239000005557 antagonist Substances 0.000 abstract description 9
238000003786 synthesis reaction Methods 0.000 abstract description 9
230000029663 wound healing Effects 0.000 abstract description 5
230000002792 vascular Effects 0.000 abstract description 3
239000000243 solution Substances 0.000 description 230
-1 trifluoromethoxy, trifluoroethoxy Chemical group 0.000 description 217
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 198
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 178
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 171
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 128
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 122
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 117
238000005481 NMR spectroscopy Methods 0.000 description 115
239000000203 mixture Substances 0.000 description 111
238000004809 thin layer chromatography Methods 0.000 description 73
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 66
125000000217 alkyl group Chemical group 0.000 description 62
239000007787 solid Substances 0.000 description 61
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238000003756 stirring Methods 0.000 description 50
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239000012267 brine Substances 0.000 description 46
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238000000034 method Methods 0.000 description 40
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210000000988 bone and bone Anatomy 0.000 description 33
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UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 30
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
150000001721 carbon Chemical group 0.000 description 30
235000002639 sodium chloride Nutrition 0.000 description 29
238000003818 flash chromatography Methods 0.000 description 28
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 26
150000002148 esters Chemical class 0.000 description 26
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 24
150000002431 hydrogen Chemical class 0.000 description 24
150000003839 salts Chemical class 0.000 description 24
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 23
229910052786 argon Inorganic materials 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
210000002997 osteoclast Anatomy 0.000 description 21
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 21
230000003042 antagnostic effect Effects 0.000 description 20
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238000001704 evaporation Methods 0.000 description 20
230000008020 evaporation Effects 0.000 description 20
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 19
238000006243 chemical reaction Methods 0.000 description 19
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239000002253 acid Substances 0.000 description 18
239000008194 pharmaceutical composition Substances 0.000 description 18
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239000011734 sodium Substances 0.000 description 17
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239000000725 suspension Substances 0.000 description 16
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
230000005764 inhibitory process Effects 0.000 description 15
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 14
238000002360 preparation method Methods 0.000 description 14
238000010992 reflux Methods 0.000 description 14
235000017557 sodium bicarbonate Nutrition 0.000 description 14
229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
229910052736 halogen Inorganic materials 0.000 description 13
150000002367 halogens Chemical class 0.000 description 13
ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 description 13
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CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
241000124008 Mammalia Species 0.000 description 12
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 12
239000002464 receptor antagonist Substances 0.000 description 12
229940044551 receptor antagonist Drugs 0.000 description 12
238000012360 testing method Methods 0.000 description 12
ZYZHMSJNPCYUTB-CYBMUJFWSA-N (1r)-n-benzyl-1-phenylethanamine Chemical compound N([C@H](C)C=1C=CC=CC=1)CC1=CC=CC=C1 ZYZHMSJNPCYUTB-CYBMUJFWSA-N 0.000 description 11
125000004657 aryl sulfonyl amino group Chemical group 0.000 description 11
230000000694 effects Effects 0.000 description 11
239000000706 filtrate Substances 0.000 description 11
239000010410 layer Substances 0.000 description 11
102000005962 receptors Human genes 0.000 description 11
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238000004458 analytical method Methods 0.000 description 10
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239000003814 drug Substances 0.000 description 10
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230000002265 prevention Effects 0.000 description 10
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 10
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 9
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206010028980 Neoplasm Diseases 0.000 description 9
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WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 8
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XADICJHFELMBGX-UHFFFAOYSA-N 5-bromo-2-methoxypyridine Chemical compound COC1=CC=C(Br)C=N1 XADICJHFELMBGX-UHFFFAOYSA-N 0.000 description 6
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NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
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230000030991 negative regulation of bone resorption Effects 0.000 description 6
125000004043 oxo group Chemical group O=* 0.000 description 6
YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 6
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 6
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125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
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VOUKBZSJHLYBLX-GOSISDBHSA-N (2S)-2-(6-aminopyridin-3-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]imidazolidin-1-yl]propanoic acid Chemical compound Nc1ccc(cn1)[C@@H](CN1CCN(CCCc2ccc3CCCNc3n2)C1=O)C(O)=O VOUKBZSJHLYBLX-GOSISDBHSA-N 0.000 description 5
NMGQIPQAXQQHLQ-AREMUKBSSA-N (2s)-2-(5-ethoxypyridin-3-yl)-3-[3-[3-[6-[(4-methoxyphenyl)methylamino]pyridin-2-yl]propyl]-2-oxoimidazolidin-1-yl]propanoic acid Chemical compound CCOC1=CN=CC([C@@H](CN2C(N(CCCC=3N=C(NCC=4C=CC(OC)=CC=4)C=CC=3)CC2)=O)C(O)=O)=C1 NMGQIPQAXQQHLQ-AREMUKBSSA-N 0.000 description 5
ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical compound C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 description 5
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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
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235000019341 magnesium sulphate Nutrition 0.000 description 5
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230000004797 therapeutic response Effects 0.000 description 1
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125000001544 thienyl group Chemical group 0.000 description 1
125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
239000003104 tissue culture media Substances 0.000 description 1
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HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
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QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications

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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- 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
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- 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
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Rheumatology (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Heart & Thoracic Surgery (AREA)
Oncology (AREA)
Cardiology (AREA)
Dermatology (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Virology (AREA)
Communicable Diseases (AREA)
Endocrinology (AREA)
Pain & Pain Management (AREA)
Ophthalmology & Optometry (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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SK916-2000A 1997-12-17 1998-12-14 Integrin receptor antagonists SK9162000A3 (en)

Applications Claiming Priority (16)

Application Number	Priority Date	Filing Date	Title
US6991097P	1997-12-17	1997-12-17
US7919798P	1998-03-24	1998-03-24
US7994498P	1998-03-30	1998-03-30
US8039798P	1998-04-02	1998-04-02
US8325198P	1998-04-27	1998-04-27
GBGB9810182.7A GB9810182D0 (en)	1998-05-13	1998-05-13	Vitronectin receptor antagonists
GBGB9810882.2A GB9810882D0 (en)	1998-05-20	1998-05-20	Vitronectin receptor antagonists
GBGB9810892.1A GB9810892D0 (en)	1998-05-20	1998-05-20	Vitronectin receptor antagonists
GBGB9811283.2A GB9811283D0 (en)	1998-05-26	1998-05-26	Vironectin receptor antagonists
GBGB9812686.5A GB9812686D0 (en)	1998-06-12	1998-06-12	Vitronectin receptor antagonists
US9262498P	1998-07-13	1998-07-13
US9258898P	1998-07-13	1998-07-13
US9994898P	1998-09-11	1998-09-11
GBGB9822331.6A GB9822331D0 (en)	1998-10-13	1998-10-13	Vitronectin receptor antagonists
GBGB9822701.0A GB9822701D0 (en)	1998-10-16	1998-10-16	Intergrin receptor antagonists
PCT/US1998/026568 WO1999031099A1 (en)	1997-12-17	1998-12-14	Integrin receptor antagonists

Publications (1)

Publication Number	Publication Date
SK9162000A3 true SK9162000A3 (en)	2001-03-12

Family

ID=27585232

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK916-2000A SK9162000A3 (en)	1997-12-17	1998-12-14	Integrin receptor antagonists

Country Status (23)

Country	Link
EP (1)	EP1040111B1 (de)
JP (2)	JP3589633B2 (de)
KR (2)	KR20010024748A (de)
AT (1)	ATE298338T1 (de)
AU (1)	AU741769B2 (de)
BG (1)	BG104601A (de)
CA (1)	CA2315189C (de)
DK (1)	DK1040111T3 (de)
EA (1)	EA003095B1 (de)
EE (1)	EE200000360A (de)
ES (1)	ES2243016T3 (de)
HU (1)	HUP0100178A3 (de)
IL (1)	IL136314A0 (de)
IS (1)	IS5513A (de)
NO (1)	NO317975B1 (de)
NZ (1)	NZ504896A (de)
PE (1)	PE20000010A1 (de)
PL (1)	PL341095A1 (de)
PT (1)	PT1040111E (de)
SI (1)	SI1040111T1 (de)
SK (1)	SK9162000A3 (de)
TR (1)	TR200001752T2 (de)
WO (1)	WO1999031099A1 (de)

Families Citing this family (59)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU736026B2 (en) *	1997-12-17	2001-07-26	Merck & Co., Inc.	Integrin receptor antagonists
GB9805655D0 (en)	1998-03-16	1998-05-13	Celltech Therapeutics Ltd	Chemical compounds
US6521626B1 (en)	1998-03-24	2003-02-18	Celltech R&D Limited	Thiocarboxamide derivatives
GB9814414D0 (en)	1998-07-03	1998-09-02	Celltech Therapeutics Ltd	Chemical compounds
JP2002522540A (ja) *	1998-08-13	2002-07-23	メルクエンドカムパニーインコーポレーテッド	インテグリン受容体拮抗薬
GB9821061D0 (en)	1998-09-28	1998-11-18	Celltech Therapeutics Ltd	Chemical compounds
GB9826174D0 (en)	1998-11-30	1999-01-20	Celltech Therapeutics Ltd	Chemical compounds
CN1398189A (zh) *	1998-12-23	2003-02-19	G.D.西尔公司	用于治疗肿瘤形成的放疗与cox－2抑制剂的联合治疗
HUP0203338A2 (hu)	1999-04-13	2003-03-28	Abbott Gmbh & Co. Kg	Integrin receptor ligandumok
US6518283B1 (en)	1999-05-28	2003-02-11	Celltech R&D Limited	Squaric acid derivatives
DK1187592T3 (da)	1999-06-02	2007-11-05	Merck & Co Inc	Alfa v-integrinreceptorantagonister
DE19936780A1 (de) *	1999-08-09	2001-02-15	Basf Ag	Neue Antagonisten von Integrinrezeptoren
US6534513B1 (en)	1999-09-29	2003-03-18	Celltech R&D Limited	Phenylalkanoic acid derivatives
JP2003510360A (ja)	1999-10-04	2003-03-18	メルクエンドカムパニーインコーポレーテッド	インテグリン受容体拮抗薬
CZ20021508A3 (cs) *	1999-11-08	2002-10-16	Merck & Co., Inc.	Způsob výroby imidazolidinonových derivátů
US6407241B1 (en)	1999-11-08	2002-06-18	Merck & Co., Inc.	Process and intermediates for the preparation of imidazolidinone αv integrin antagonists
GB2356630A (en)	1999-11-10	2001-05-30	Merck & Co Inc	Intermediates used in the preparation of tetrahydronaphthyridine
JP2003514908A (ja)	1999-11-23	2003-04-22	メルクエンドカムパニーインコーポレーテッド	テトラヒドロ−［１，８］−ナフチリジンに向けた方法および中間体
US6849639B2 (en)	1999-12-14	2005-02-01	Amgen Inc.	Integrin inhibitors and their methods of use
US6455539B2 (en)	1999-12-23	2002-09-24	Celltech R&D Limited	Squaric acid derivates
WO2001053297A1 (en)	2000-01-20	2001-07-26	Merck & Co., Inc.	Alpha v integrin receptor antagonists
DE60130910T2 (de)	2000-04-17	2008-07-10	Ucb Pharma, S.A.	Enamin-derivate als zell-adhäsionsmoleküle
US6403608B1 (en)	2000-05-30	2002-06-11	Celltech R&D, Ltd.	3-Substituted isoquinolin-1-yl derivatives
US6545013B2 (en)	2000-05-30	2003-04-08	Celltech R&D Limited	2,7-naphthyridine derivatives
JP2004502762A (ja)	2000-07-07	2004-01-29	セルテック　アール　アンド　ディ　リミテッド	二環性ヘテロ芳香環を含有するインテグリンアンタゴニストとしてのスクエア酸誘導体
JP2004505110A (ja)	2000-08-02	2004-02-19	セルテック　アール　アンド　ディ　リミテッド	３位置換イソキノリン−１−イル誘導体
EP1322310A4 (de) *	2000-09-13	2004-09-15	Merck & Co Inc	Alpha-v-integrin-rezeptorantagonisten
AU2001292598B2 (en)	2000-09-14	2006-06-29	Merck & Co., Inc.	Alpha V integrin receptor antagonists
WO2002053099A2 (en) *	2001-01-03	2002-07-11	Merck & Co., Inc.	Methods and compositions for treating periodontal disease
ES2200617B1 (es)	2001-01-19	2005-05-01	Almirall Prodesfarma, S.A.	Derivados de urea como antagonistas de integrinas alfa 4.
ES2366775T3 (es)	2001-04-24	2011-10-25	Merck Patent Gmbh	POLITERAPIA UTILIZANDO AGENTES ANTIANGIOGÉNICOS Y TNF(alfa).
US6855724B2 (en)	2002-04-08	2005-02-15	Agouron Pharmaceuticals, Inc.	Tropane derivatives useful in therapy
UA87854C2 (en)	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
EP1798224A1 (de) *	2004-10-05	2007-06-20	Shionogi Co., Ltd.	Biarylderivat
AU2007207465B2 (en)	2006-01-18	2012-12-06	Merck Patent Gmbh	Specific therapy using integrin ligands for treating cancer
DE102006024024A1 (de)	2006-05-23	2007-11-29	Bayer Healthcare Aktiengesellschaft	Substituierte Arylimidazolone und -triazolone sowie ihre Verwendung
BRPI0806596A2 (pt)	2007-01-18	2013-07-23	Merck Patent Ges Mit Berchraenkter Haftung	medicamento e terapia especÍfica usando-se ligantes de integrina para o tratamento de cÂncer
WO2009114776A2 (en) *	2008-03-14	2009-09-17	Visen Medical, Inc.	Integrin targeting agents and methods of using same
DE102008060967A1 (de)	2008-12-06	2010-06-10	Bayer Schering Pharma Aktiengesellschaft	Substituierte Phenylsulfonyltriazolone und ihre Verwendung
DE102010001064A1 (de)	2009-03-18	2010-09-23	Bayer Schering Pharma Aktiengesellschaft	Substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung
EP2445534A2 (de)	2009-05-25	2012-05-02	Merck Patent GmbH	Kontinuierliche verabreichung von cilengitid in der krebstherapie
PL2539326T3 (pl)	2010-02-27	2017-10-31	Bayer Ip Gmbh	Połączone bis-arylem arylotriazolony i ich zastosowanie
DE102010040187A1 (de)	2010-09-02	2012-03-08	Bayer Schering Pharma Aktiengesellschaft	Substituierte N-Phenethyl-triazolonacetamide und ihre Verwendung
DE102010040924A1 (de)	2010-09-16	2012-03-22	Bayer Schering Pharma Aktiengesellschaft	Substituierte Phenylacet- und Phenylpropanamide und ihre Verwendung
US8901144B2 (en)	2013-02-07	2014-12-02	Scifluor Life Sciences, Llc	Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives
WO2014124302A1 (en)	2013-02-07	2014-08-14	Scifluor Life Sciences, Llc	Fluorinated integrin antagonists
EP3050878B1 (de)	2013-09-24	2021-10-27	FUJIFILM Corporation	Neuartige stickstoffhaltige verbindung oder salz davon oder metallkomplex davon
ES2864079T3 (es)	2014-05-30	2021-10-13	Pfizer	Derivados de carbonitrilo como moduladores selectivos del receptor de andrógenos
KR20170081178A (ko)	2014-11-03	2017-07-11	바이엘 파마 악티엔게젤샤프트	히드록시알킬-치환된 페닐트리아졸 유도체 및 그의 용도
CN113855703B (zh) *	2014-12-10	2025-11-25	特里赛达公司	用于口服施用的质子结合聚合物
WO2016134223A2 (en) *	2015-02-19	2016-08-25	Scifluor Life Sciences, Inc.	Fluorinated tetrahydronaphthyridinyl nonanoic acid derivatives and uses thereof
WO2017189828A1 (en) *	2016-04-27	2017-11-02	Scifluor Life Sciences, Inc.	Nonanoic and decanoic acid derivatives and uses thereof
US9988367B2 (en)	2016-05-03	2018-06-05	Bayer Pharma Aktiengesellschaft	Amide-substituted pyridinyltriazole derivatives and uses thereof
SG11201907820SA (en)	2017-02-28	2019-09-27	Morphic Therapeutic Inc	Inhibitors of (alpha-v)(beta-6) integrin
US11046685B2 (en)	2017-02-28	2021-06-29	Morphic Therapeutic, Inc.	Inhibitors of (α-v)(β-6) integrin
CA3109534A1 (en)	2018-08-29	2020-03-05	Morphic Therapeutic, Inc.	Inhibiting .alpha.v .beta.6 integrin
UY38352A (es)	2018-08-29	2020-03-31	Morphic Therapeutic Inc	Inhibidores de integrina alfavbeta6
EP3843727A4 (de)	2018-08-29	2022-08-17	Morphic Therapeutic, Inc.	Inhibitoren von (alpha-v)(beta-6)-integrin
WO2023275715A1 (en)	2021-06-30	2023-01-05	Pfizer Inc.	Metabolites of selective androgen receptor modulators

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1598073A (en) *	1976-12-18	1981-09-16	Beecham Group Ltd	8,10,12-triazaprostaglandins
AU4806879A (en) *	1978-06-15	1979-12-20	Beecham Group Limited	1,2,4 triazole derivatives
DE3042466A1 (de) *	1980-11-11	1982-06-16	A. Nattermann & Cie GmbH, 5000 Köln	N-substituierte (omega) -(2-oxo-4-imidazolin-l-yl)-alkansaeure-derivate, verfahren zu ihrer herstellung und diese enthaltende pharmazeutische praeparate
EP0531382A1 (de) *	1990-05-25	1993-03-17	G.D. Searle & Co.	N-substituierte 1,2,4-triazolonverbindungen zur behandlung von herz-kreislauf-störungen
US5416099A (en) *	1991-10-29	1995-05-16	Merck & Co., Inc.	Fibrinogen receptor antagonists
JP2001527506A (ja) *	1992-02-11	2001-12-25	スミスクライン・ビーチャム・コーポレイション	ＣｏＡ−ＩＴおよびＰＡＦ阻害剤
CA2190870A1 (en) *	1994-05-27	1995-12-07	George D. Hartman	Compounds for inhibiting osteoclast-mediated bone resorption

1998
- 1998-12-14 IL IL13631498A patent/IL136314A0/xx unknown
- 1998-12-14 SI SI9830777T patent/SI1040111T1/xx unknown
- 1998-12-14 CA CA002315189A patent/CA2315189C/en not_active Expired - Lifetime
- 1998-12-14 TR TR2000/01752T patent/TR200001752T2/xx unknown
- 1998-12-14 AU AU19144/99A patent/AU741769B2/en not_active Expired
- 1998-12-14 PT PT98963915T patent/PT1040111E/pt unknown
- 1998-12-14 AT AT98963915T patent/ATE298338T1/de active
- 1998-12-14 NZ NZ504896A patent/NZ504896A/xx unknown
- 1998-12-14 EA EA200000653A patent/EA003095B1/ru not_active IP Right Cessation
- 1998-12-14 KR KR1020007006653A patent/KR20010024748A/ko not_active Abandoned
- 1998-12-14 ES ES98963915T patent/ES2243016T3/es not_active Expired - Lifetime
- 1998-12-14 SK SK916-2000A patent/SK9162000A3/sk unknown
- 1998-12-14 JP JP2000539023A patent/JP3589633B2/ja not_active Expired - Lifetime
- 1998-12-14 DK DK98963915T patent/DK1040111T3/da active
- 1998-12-14 EE EEP200000360A patent/EE200000360A/xx unknown
- 1998-12-14 HU HU0100178A patent/HUP0100178A3/hu unknown
- 1998-12-14 PL PL98341095A patent/PL341095A1/xx not_active Application Discontinuation
- 1998-12-14 WO PCT/US1998/026568 patent/WO1999031099A1/en not_active Ceased
- 1998-12-14 KR KR10-2003-7005778A patent/KR20030048081A/ko not_active Withdrawn
- 1998-12-14 EP EP98963915A patent/EP1040111B1/de not_active Expired - Lifetime
- 1998-12-17 PE PE1998001244A patent/PE20000010A1/es not_active Application Discontinuation
2000
- 2000-05-26 IS IS5513A patent/IS5513A/is unknown
- 2000-06-16 NO NO20003113A patent/NO317975B1/no not_active IP Right Cessation
- 2000-07-13 BG BG104601A patent/BG104601A/bg unknown
2004
- 2004-06-24 JP JP2004185935A patent/JP2004300158A/ja active Pending

Also Published As

Publication number	Publication date
ES2243016T3 (es)	2005-11-16
JP3589633B2 (ja)	2004-11-17
EA200000653A1 (ru)	2000-12-25
DK1040111T3 (da)	2005-10-10
NO20003113L (no)	2000-08-16
EE200000360A (et)	2001-12-17
NO20003113D0 (no)	2000-06-16
TR200001752T2 (tr)	2000-12-21
NO317975B1 (no)	2005-01-17
AU741769B2 (en)	2001-12-06
EP1040111A1 (de)	2000-10-04
PE20000010A1 (es)	2000-01-29
EA003095B1 (ru)	2002-12-26
HUP0100178A2 (hu)	2001-11-28
JP2002508374A (ja)	2002-03-19
IS5513A (is)	2000-05-26
CA2315189A1 (en)	1999-06-24
PT1040111E (pt)	2005-10-31
HUP0100178A3 (en)	2002-12-28
WO1999031099A1 (en)	1999-06-24
SI1040111T1 (en)	2005-10-31
CA2315189C (en)	2005-04-19
PL341095A1 (en)	2001-03-26
KR20010024748A (ko)	2001-03-26
IL136314A0 (en)	2001-05-20
NZ504896A (en)	2002-10-25
ATE298338T1 (de)	2005-07-15
EP1040111B1 (de)	2005-06-22
KR20030048081A (ko)	2003-06-18
BG104601A (bg)	2001-01-31
JP2004300158A (ja)	2004-10-28
AU1914499A (en)	1999-07-05

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EP1040111B1 (de)	2005-06-22	Integrin-rezeptor-antagonisten
US6017926A (en)	2000-01-25	Integrin receptor antagonists
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EP1040098B1 (de)	2005-04-27	Integrin-rezeptor-antagonisten
AU724191B2 (en)	2000-09-14	Integrin antagonists
US6268378B1 (en)	2001-07-31	Integrin receptor antagonists
EP1044001B1 (de)	2005-07-06	Integrinrezeptor antagonisten
EP1047425A1 (de)	2000-11-02	Integrinrezeptor antagonisten
SK17442001A3 (sk)	2002-03-05	Deriváty kyseliny nonánovej, farmaceutický prostriedok s ich obsahom a ich použitie
AU747503B2 (en)	2002-05-16	Benzazepine derivatives as alpha-V integrin receptor antagonists
US6211184B1 (en)	2001-04-03	Integrin antagonists
CZ20002269A3 (cs)	2001-01-17	Látky antagonizující receptor íntegrinu
EP1322310A1 (de)	2003-07-02	Alpha-v-integrin-rezeptorantagonisten
AU2001290884A1 (en)	2002-06-13	Alpha V integrin receptor antagonists
CZ20002276A3 (cs)	2001-03-14	Látky antagonizující receptor integrinu