OA11388A - Hydroxamic acid derivatives as matrix metalloprotease (MMP) inhibitors. - Google Patents

Hydroxamic acid derivatives as matrix metalloprotease (MMP) inhibitors. Download PDF

Info

Publication number: OA11388A
Authority: OA; OAPI
Prior art keywords: préparation; brs; title compound; lrms; mmol
Prior art date: 1997-12-05

Application number

OA1200000160A

Other languages

English (en)

Inventor

Kevin Neil Dack

Gavin Alistair Whitlock

Original Assignee

Pfizer

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.)

1997-12-05

Filing date

2000-05-31

Publication date

2004-04-14

2000-05-31 Application filed by Pfizer filed Critical Pfizer

2004-04-14 Publication of OA11388A publication Critical patent/OA11388A/en

Links

239000003112 inhibitor Substances 0.000 title claims description 14
239000002253 acid Substances 0.000 title description 28
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 title description 4
239000011159 matrix material Substances 0.000 title description 3
102000005741 Metalloproteases Human genes 0.000 title description 2
108010006035 Metalloproteases Proteins 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 325
239000001257 hydrogen Substances 0.000 claims abstract description 36
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 36
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 27
125000000217 alkyl group Chemical group 0.000 claims abstract description 24
125000003545 alkoxy group Chemical group 0.000 claims abstract description 18
125000005843 halogen group Chemical group 0.000 claims abstract description 12
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 11
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 11
229910052799 carbon Inorganic materials 0.000 claims abstract description 10
229940124761 MMP inhibitor Drugs 0.000 claims abstract description 9
125000003342 alkenyl group Chemical group 0.000 claims abstract description 8
125000005842 heteroatom Chemical group 0.000 claims abstract description 7
208000017520 skin disease Diseases 0.000 claims abstract description 7
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125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 6
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238000000034 method Methods 0.000 claims description 171
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 144
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 142
239000000203 mixture Substances 0.000 claims description 85
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 64
-1 -136- thienyl Chemical group 0.000 claims description 59
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 32
239000002904 solvent Substances 0.000 claims description 27
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 24
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VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 claims description 15
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WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 14
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JRIUEEGXFJPYTG-UHFFFAOYSA-N n-hydroxy-2-[4-[4-[3-(2-methoxyethoxy)phenyl]-3-methylphenyl]piperidin-1-yl]sulfonyl-2-methylpropanamide Chemical compound COCCOC1=CC=CC(C=2C(=CC(=CC=2)C2CCN(CC2)S(=O)(=O)C(C)(C)C(=O)NO)C)=C1 JRIUEEGXFJPYTG-UHFFFAOYSA-N 0.000 claims 1
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239000011686 zinc sulphate Substances 0.000 description 1
235000009529 zinc sulphate Nutrition 0.000 description 1

Classifications

- 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
- C07D401/02—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 two hetero rings
- C07D401/10—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 two hetero rings linked by a carbon chain containing aromatic rings
- 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
- 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
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
- 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
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- 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
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
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Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Pharmacology & Pharmacy (AREA)
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Heart & Thoracic Surgery (AREA)
Dermatology (AREA)
Rheumatology (AREA)
Immunology (AREA)
Physical Education & Sports Medicine (AREA)
Pain & Pain Management (AREA)
Orthopedic Medicine & Surgery (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Oncology (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)
Enzymes And Modification Thereof (AREA)
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OA1200000160A 1997-12-05 2000-05-31 Hydroxamic acid derivatives as matrix metalloprotease (MMP) inhibitors. OA11388A (en)

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Application Number	Priority Date	Filing Date	Title
GBGB9725782.8A GB9725782D0 (en)	1997-12-05	1997-12-05	Therapeutic agents

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OA1200000160A OA11388A (en)	1997-12-05	2000-05-31	Hydroxamic acid derivatives as matrix metalloprotease (MMP) inhibitors.

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EP (1)	EP1036062B1 (cs)
JP (1)	JP3445242B2 (cs)
KR (1)	KR100372990B1 (cs)
CN (1)	CN1281433A (cs)
AP (1)	AP930A (cs)
AR (1)	AR016429A1 (cs)
AT (1)	ATE257151T1 (cs)
AU (1)	AU741859B2 (cs)
BG (1)	BG104506A (cs)
BR (1)	BR9813360A (cs)
CA (1)	CA2312935C (cs)
CZ (1)	CZ20002037A3 (cs)
DE (1)	DE69820906T2 (cs)
DK (1)	DK1036062T3 (cs)
DZ (1)	DZ2666A1 (cs)
EA (1)	EA002882B1 (cs)
ES (1)	ES2212373T3 (cs)
GB (1)	GB9725782D0 (cs)
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HR (1)	HRP20000373A2 (cs)
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MA (1)	MA26571A1 (cs)
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NZ (1)	NZ504421A (cs)
OA (1)	OA11388A (cs)
PA (1)	PA8463501A1 (cs)
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TN (1)	TNSN98216A1 (cs)
TR (1)	TR200001611T2 (cs)
UA (1)	UA52791C2 (cs)
UY (2)	UY25280A1 (cs)
WO (1)	WO1999029667A1 (cs)
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ZA (1)	ZA9811112B (cs)

Families Citing this family (336)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9801690D0 (en) *	1998-01-27	1998-03-25	Pfizer Ltd	Therapeutic agents
PL341984A1 (en) *	1998-01-28	2001-05-07	Shionogi & Co	Novel tricycle compounds
US6800646B1 (en)	1999-02-08	2004-10-05	Pharmacia Corporation	Sulfamato hydroxamic acid metalloprotease inhibitor
AU775701B2 (en)	1999-02-08	2004-08-12	G.D. Searle & Co.	Sulfamato hydroxamic acid metalloprotease inhibitor
US6511993B1 (en) *	1999-06-03	2003-01-28	Kevin Neil Dack	Metalloprotease inhibitors
GB9912961D0 (en) *	1999-06-03	1999-08-04	Pfizer Ltd	Metalloprotease inhibitors
UA74803C2 (uk)	1999-11-11	2006-02-15	Осі Фармасьютікалз, Інк.	Стійкий поліморф гідрохлориду n-(3-етинілфеніл)-6,7-біс(2-метоксіетокси)-4-хіназолінаміну, спосіб його одержання (варіанти) та фармацевтичне застосування
EP1261595A1 (en) *	2000-02-21	2002-12-04	AstraZeneca AB	Arylpiperazines and arylpiperidines and their use as metalloproteinase inhibiting agents
JO2409B1 (en)	2000-11-21	2007-06-17	شركة جانسين فارماسوتيكا ان. في	Second-phenyl carboxy amides are useful as lipid-lowering agents
NZ527302A (en)	2001-01-05	2006-10-27	Abgenix Inc	Antibodies to insulin-like growth factor I receptor
US6821972B2 (en)	2001-03-30	2004-11-23	Pfizer Inc.	3-heterocyclylpropanohydroxamic acid PCP inhibitors
GB0108102D0 (en) *	2001-03-30	2001-05-23	Pfizer Ltd	Compounds
WO2003000194A2 (en)	2001-06-21	2003-01-03	Pfizer Inc.	Thienopyridine and thienopyrimidine anticancer agents
GB0119474D0 (en) *	2001-08-09	2001-10-03	Astrazeneca Ab	Compounds
AR039067A1 (es)	2001-11-09	2005-02-09	Pfizer Prod Inc	Anticuerpos para cd40
EP1463505A2 (en) *	2001-12-13	2004-10-06	Abbott Laboratories	3-(phenyl-alkoxy)-5-(phenyl)-pyridine derivatives and related compounds as kinase inhibitors for the treatment of cancer
SG2013013339A (en)	2002-03-13	2014-12-30	Array Biopharma Inc	N3 alkylated benzimidazole derivatives as mek inhibitors
CA2483314A1 (en)	2002-04-25	2003-11-06	Pharmacia Corporation	Piperidinyl-and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors
US20050209278A1 (en) *	2002-04-25	2005-09-22	Mcdonald Joseph J	Piperidinyl- and piperazinyl-sulfonylmethyl hydroxamic acids and their use as protease inhibitors
UA77303C2 (en)	2002-06-14	2006-11-15	Pfizer	Derivatives of thienopyridines substituted by benzocondensed heteroarylamide useful as therapeutic agents, pharmaceutical compositions and methods for their use
US20040167182A1 (en) *	2002-06-25	2004-08-26	Becker Daniel P.	Hydroxamic acid and amide compounds and their use as protease inhibitors
MXPA05005474A (es) *	2002-11-25	2005-07-25	Pharmacia Corp	Acidos y amidas heteroarilsulfonilmetil hidroxamicos y su uso como inhibidores de proteasas.
DK1587821T6 (da) *	2002-12-19	2025-05-26	Scripps Research Inst	Sammensætninger og fremgangsmåder til stabilisering af trans-thyretin og inhibering af transthyretin-fejlfoldning
AU2003286321A1 (en)	2002-12-19	2004-07-14	Pfizer Inc.	2-(1h-indazol-6-ylamino)-benzamide compounds as protein kinases inhibitors useful for the treatment of ophtalmic diseases
WO2004060346A2 (en)	2002-12-30	2004-07-22	Angiotech International Ag	Drug delivery from rapid gelling polymer composition
PT2476667E (pt)	2003-02-26	2014-09-18	Sugen Inc	Compostos de aminoheteroarilo como inibidores da proteína quinase
HN2004000285A (es)	2003-08-04	2006-04-27	Pfizer Prod Inc	ANTICUERPOS DIRIGIDOS A c-MET
US7144907B2 (en)	2003-09-03	2006-12-05	Array Biopharma Inc.	Heterocyclic inhibitors of MEK and methods of use thereof
AR045563A1 (es)	2003-09-10	2005-11-02	Warner Lambert Co	Anticuerpos dirigidos a m-csf
KR101190912B1 (ko)	2003-11-19	2012-10-12	어레이 바이오파마 인크.	Ｍｅｋ의 헤테로시클릭 억제제 및 그의 사용 방법
WO2005112913A1 (en) *	2004-05-20	2005-12-01	The Scripps Research Institute	Transthyretin stabilization
CN101014365B (zh)	2004-07-16	2011-04-13	辉瑞产品公司	使用抗-igf-1r抗体联合治疗非血液的恶性肿瘤
JP4242911B2 (ja)	2004-08-26	2009-03-25	ファイザー・インク	プロテインキナーゼ阻害薬としてのエナンチオピュアなアミノヘテロアリール化合物
MY146381A (en)	2004-12-22	2012-08-15	Amgen Inc	Compositions and methods relating relating to anti-igf-1 receptor antibodies
US7429667B2 (en)	2005-01-20	2008-09-30	Ardea Biosciences, Inc.	Phenylamino isothiazole carboxamidines as MEK inhibitors
TWI441637B (zh)	2005-05-18	2014-06-21	Array Biopharma Inc	Ｍｅｋ雜環抑制劑及其使用方法
US8101799B2 (en)	2005-07-21	2012-01-24	Ardea Biosciences	Derivatives of N-(arylamino) sulfonamides as inhibitors of MEK
WO2007016525A2 (en)	2005-07-29	2007-02-08	Resverlogix Corp.	Pharmaceutical compositions for the prevention and treatment of complex diseases and their delivery by insertable medical devices
AU2006292278B2 (en)	2005-09-20	2012-03-08	Osi Pharmaceuticals, Inc.	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
TWI405756B (zh)	2005-12-21	2013-08-21	Array Biopharma Inc	新穎硫酸氫鹽
US7842836B2 (en)	2006-04-11	2010-11-30	Ardea Biosciences	N-aryl-N'alkyl sulfamides as MEK inhibitors
AU2007237901B2 (en)	2006-04-18	2012-07-05	Ardea Biosciences, Inc.	Pyridone sulfonamides and pyridone sulfamides as MEK inhibitors
WO2008034016A2 (en) *	2006-09-15	2008-03-20	Foldrx Pharmaceuticals, Inc.	Assays for detecting native-state proteins and identifying compounds that modulate the stability of native-state proteins
WO2008075196A1 (en)	2006-12-15	2008-06-26	Pfizer Products Inc.	Benzimidazole derivatives
ES2547303T3 (es)	2007-01-19	2015-10-05	Ardea Biosciences, Inc.	Inhibidores de MEK
PT2118074E (pt)	2007-02-01	2014-03-20	Resverlogix Corp	Compostos para a prevenção e tratamento de doenças cardiovasculares
DK2146779T3 (en)	2007-04-18	2016-11-28	Pfizer Prod Inc	Sulfonylamid derivatives to treat abnormal cell growth.
US8530463B2 (en)	2007-05-07	2013-09-10	Hale Biopharma Ventures Llc	Multimodal particulate formulations
CA2694646C (en)	2007-07-30	2017-09-05	Ardea Biosciences, Inc.	Combinations of mek inhibitors and raf kinase inhibitors and uses thereof
TWI441820B (zh)	2007-12-19	2014-06-21	Genentech Inc	５－苯胺咪唑并吡啶及使用方法
CA2708176A1 (en)	2007-12-21	2009-07-02	Genentech, Inc.	Azaindolizines and methods of use
US8193182B2 (en)	2008-01-04	2012-06-05	Intellikine, Inc.	Substituted isoquinolin-1(2H)-ones, and methods of use thereof
BRPI0906473A8 (pt)	2008-01-04	2016-02-10	Intellikine Inc	Certas entidades químicas, composições e métodos
WO2009114870A2 (en)	2008-03-14	2009-09-17	Intellikine, Inc.	Kinase inhibitors and methods of use
US20090258865A1 (en)	2008-03-28	2009-10-15	Hale Biopharma Ventures, Llc	Administration of benzodiazepine compositions
US8114995B2 (en)	2008-06-26	2012-02-14	Resverlogix Corp.	Methods of preparing quinazolinone derivatives
MX2011000216A (es)	2008-07-08	2011-03-29	Intellikine Inc	Inhibidores de cinasa y metodos para su uso.
EP2147684A1 (en)	2008-07-22	2010-01-27	Bracco Imaging S.p.A	Diagnostic Agents Selective Against Metalloproteases
EP2149568A1 (en)	2008-07-22	2010-02-03	Bracco Imaging S.p.A	Aryl-sulphonamidic dimers as metalloproteases inhibitors
CA2737597C (en)	2008-10-16	2017-03-14	University Of Pittsburgh-Of The Commonwealth System Of Higher Education	Fully human antibodies to high molecular weight-melanoma associated antigen and uses thereof
US8476431B2 (en)	2008-11-03	2013-07-02	Itellikine LLC	Benzoxazole kinase inhibitors and methods of use
ES2542835T3 (es)	2009-01-08	2015-08-12	Resverlogix Corporation	Compuestos para la prevención y el tratamiento de enfermedades cardiovasculares
CA3014224C (en)	2009-02-05	2022-05-24	Immunogen, Inc.	Condensed benzodiazepine-indoline derivatives and processes to prepare said derivatives
SG172857A1 (en)	2009-02-09	2011-08-29	Supergen Inc	Pyrrolopyrimidinyl axl kinase inhibitors
US20120189641A1 (en)	2009-02-25	2012-07-26	OSI Pharmaceuticals, LLC	Combination anti-cancer therapy
US20110171124A1 (en)	2009-02-26	2011-07-14	Osi Pharmaceuticals, Inc.	In situ methods for monitoring the EMT status of tumor cells in vivo
US8642834B2 (en)	2009-02-27	2014-02-04	OSI Pharmaceuticals, LLC	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
WO2010098866A1 (en)	2009-02-27	2010-09-02	Supergen, Inc.	Cyclopentathiophene/cyclohexathiophene dna methyltransferase inhibitors
JP2012519282A (ja)	2009-02-27	2012-08-23	オーエスアイ・ファーマシューティカルズ，エルエルシー	間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法
WO2010099138A2 (en)	2009-02-27	2010-09-02	Osi Pharmaceuticals, Inc.	Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation
NZ617779A (en)	2009-03-18	2015-08-28	Resverlogix Corp	Novel anti-inflammatory agents
US8673919B2 (en)	2009-03-27	2014-03-18	Ardea Biosciences, Inc.	Dihydropyridin sulfonamides and dihydropyridin sulfamides as MEK inhibitors
US9757368B2 (en)	2009-04-22	2017-09-12	Resverlogix Corp.	Anti-inflammatory agents
JP5789252B2 (ja)	2009-05-07	2015-10-07	インテリカイン，エルエルシー	複素環式化合物およびその使用
WO2011014726A1 (en)	2009-07-31	2011-02-03	Osi Pharmaceuticals, Inc.	Mtor inhibitor and angiogenesis inhibitor combination therapy
UA111579C2 (uk)	2009-08-17	2016-05-25	Інтеллікіне Ллк	ГЕТЕРОЦИКЛІЧНІ ПОХІДНІ 2-АМІНОБЕНЗО[d]ОКСАЗОЛУ, ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ НА ЇХ ОСНОВІ ТА ЇХ ЗАСТОСУВАННЯ ДЛЯ ЛІКУВАННЯ ЗАХВОРЮВАННЯ, ПОВ'АНОГО З РІ3-КІНАЗОЮ
US20120157471A1 (en)	2009-09-01	2012-06-21	Pfizer Inc.	Benzimidazole derivatives
CA2814617C (en)	2009-10-13	2017-12-19	Allostem Therapeutics Llc	Novel mek inhibitors, useful in the treatment of diseases
WO2011049625A1 (en)	2009-10-20	2011-04-28	Mansour Samadpour	Method for aflatoxin screening of products
LT2496567T (lt)	2009-11-05	2017-11-27	Rhizen Pharmaceuticals S.A.	Nauji benzopirano kinazės moduliatoriai
AR080154A1 (es)	2010-02-10	2012-03-14	Immunogen Inc	Anticuerpos cd20 y su utilizacion
ES2607806T5 (es)	2010-02-12	2024-10-07	Pfizer	Sales y polimorfos de 8-fluoro-2-{4-[(metilamino}metil]fenil}-1,3,4,5-tetrahidro-6H-azepino[5,4,3-cd]indol-6-ona
AU2011223643A1 (en)	2010-03-03	2012-06-28	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
AU2011223655A1 (en)	2010-03-03	2012-06-28	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors
JP5960688B2 (ja)	2010-05-17	2016-08-02	インコゼンセラピューティクスプライベートリミテッド	プロテインキナーゼ調節物質としての新規３，５−二置換−３ｈ−［１，２，３］トリアゾロ［４，５−ｂ］ピリジン化合物
JP5951600B2 (ja)	2010-05-21	2016-07-13	インフィニティーファーマシューティカルズ，インコーポレイテッド	キナーゼ調節のための、化合物、組成物および方法
CN103068851B (zh)	2010-06-16	2015-03-11	高等教育联邦系统-匹兹堡大学	内质蛋白的抗体及其用途
US9738604B2 (en)	2010-09-03	2017-08-22	Duke University	Ethynylbenzene derivatives
US9056865B2 (en)	2010-10-20	2015-06-16	Pfizer Inc.	Pyridine-2-derivatives as smoothened receptor modulators
WO2012064973A2 (en)	2010-11-10	2012-05-18	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
EP3238722B1 (en)	2011-01-10	2019-03-13	Infinity Pharmaceuticals, Inc.	Solid forms of isoquinolinones
WO2012106556A2 (en)	2011-02-02	2012-08-09	Amgen Inc.	Methods and compositons relating to inhibition of igf-1r
SI2675480T1 (sl)	2011-02-15	2019-05-31	Immunogen, Inc.	Metode priprave konjugatov
WO2012116040A1 (en)	2011-02-22	2012-08-30	OSI Pharmaceuticals, LLC	Biological markers predictive of anti-cancer response to insulin-like growth factor-1 receptor kinase inhibitors in hepatocellular carcinoma
WO2012116237A2 (en)	2011-02-23	2012-08-30	Intellikine, Llc	Heterocyclic compounds and uses thereof
WO2012142164A1 (en)	2011-04-12	2012-10-18	The United States Of America, As Represented By The Secretary, Department Of Health & Human Services	Human monoclonal antibodies that bind insulin-like growth factor (igf) i and ii
US20140178368A1 (en)	2011-04-19	2014-06-26	Leslie Lynne SHARP	Combinations of anti-4-1bb antibodies and adcc-inducing antibodies for the treatment of cancer
JP2014519813A (ja)	2011-04-25	2014-08-21	オーエスアイ・ファーマシューティカルズ，エルエルシー	癌薬剤発見、診断、および治療におけるｅｍｔ遺伝子シグネチャーの使用
PT2705029T (pt)	2011-05-04	2019-02-01	Rhizen Pharmaceuticals S A	Novos compostos como moduladores de proteína quinases
PT3415139T (pt)	2011-06-14	2022-06-20	Neurelis Inc	Administração de benzodiazepina
EP2734520B1 (en)	2011-07-19	2016-09-14	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
US9056877B2 (en)	2011-07-19	2015-06-16	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
DK2734205T3 (en)	2011-07-21	2018-06-14	Tolero Pharmaceuticals Inc	Heterocyclic Protein Kinase Inhibitors
PE20141371A1 (es)	2011-08-29	2014-10-13	Infinity Pharmaceuticals Inc	Compuestos heterociclicos y usos de los mismos
WO2013038351A1 (en)	2011-09-16	2013-03-21	Pfizer Inc.	Solid forms of a transthyretin dissociation inhibitor
MD20140023A2 (ro)	2011-09-22	2014-06-30	Pfizer Inc.	Derivaţi de pirolpirimidină şi purină
US9630979B2 (en)	2011-09-29	2017-04-25	Infinity Pharmaceuticals, Inc.	Inhibitors of monoacylglycerol lipase and methods of their use
ES2654160T3 (es)	2011-10-04	2018-02-12	Igem Therapeutics Limited	Anticuerpos de IgE anti-HMW-MAA
PT2773354T (pt)	2011-11-01	2019-07-17	Resverlogix Corp	Formulações orais de libertação imediata para quinazolinonas substituídas
MX2014005570A (es)	2011-11-08	2014-05-30	Pfizer	El uso de anticuerpos anti factor estimulante de la colonia de macrofagos para tratar trastornos inflamatorios.
US9452215B2 (en)	2012-02-22	2016-09-27	The Regents Of The University Of Colorado	Bourvadin derivatives and therapeutic uses thereof
WO2013126617A1 (en)	2012-02-22	2013-08-29	The Regents Of The University Of Colorado, A Body Corporate	Bouvardin derivatives and therapeutic uses thereof
CN104321322A (zh)	2012-03-30	2015-01-28	理森制药股份公司	作为c-met蛋白激酶调节剂的新型3,5-二取代-3h-咪唑并[4,5-b]吡啶和3,5-二取代-3h-[1,2,3]三唑并[4,5-b]吡啶化合物
WO2013152252A1 (en)	2012-04-06	2013-10-10	OSI Pharmaceuticals, LLC	Combination anti-cancer therapy
US8940742B2 (en)	2012-04-10	2015-01-27	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
US9738724B2 (en)	2012-06-08	2017-08-22	Sutro Biopharma, Inc.	Antibodies comprising site-specific non-natural amino acid residues, methods of their preparation and methods of their use
EP3135690A1 (en)	2012-06-26	2017-03-01	Sutro Biopharma, Inc.	Modified fc proteins comprising site-specific non-natural amino acid residues, conjugates of the same, methods of their preparation and methods of their use
HK1211208A1 (zh)	2012-08-22	2016-05-20	Immunogen, Inc.	細胞毒性苯並二氮呯衍生物
SI2890402T1 (sl)	2012-08-31	2019-07-31	Sutro Biopharma, Inc.	Modificirane aminokisline vsebujoče acido skupino
EP2909181B1 (en)	2012-10-16	2017-08-09	Tolero Pharmaceuticals, Inc.	Pkm2 modulators and methods for their use
RU2702908C2 (ru)	2012-11-01	2019-10-14	Инфинити Фармасьютикалз, Инк.	Лечение злокачественных опухолей с использованием модуляторов изоформ pi3-киназы
US9765039B2 (en)	2012-11-21	2017-09-19	Zenith Epigenetics Ltd.	Biaryl derivatives as bromodomain inhibitors
US9073878B2 (en)	2012-11-21	2015-07-07	Zenith Epigenetics Corp.	Cyclic amines as bromodomain inhibitors
JP2016507496A (ja)	2012-12-21	2016-03-10	ゼニス・エピジェネティクス・コーポレイションＺｅｎｉｔｈＥｐｉｇｅｎｅｔｉｃｓＣｏｒｐ．	ブロモドメイン阻害剤としての新規複素環式化合物
HK1219422A1 (zh)	2013-02-28	2017-04-07	Immunogen, Inc.	包含细胞结合剂及细胞毒素剂的轭合物
HK1219423A1 (zh)	2013-02-28	2017-04-07	Immunogen, Inc.	包含细胞结合剂及细胞毒素剂的轭合物
PT2970205T (pt)	2013-03-14	2019-08-26	Tolero Pharmaceuticals Inc	Inibidores da jak2 e da alk2 e métodos para a sua utilização
HK1219421A1 (zh)	2013-03-15	2017-04-07	因特利凯有限责任公司	激酶抑制剂的组合及其用途
WO2014143659A1 (en)	2013-03-15	2014-09-18	Araxes Pharma Llc	Irreversible covalent inhibitors of the gtpase k-ras g12c
US9227978B2 (en)	2013-03-15	2016-01-05	Araxes Pharma Llc	Covalent inhibitors of Kras G12C
NZ629037A (en)	2013-03-15	2017-04-28	Infinity Pharmaceuticals Inc	Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
TW201524952A (zh)	2013-03-15	2015-07-01	Araxes Pharma Llc	Ｋｒａｓｇ１２ｃ之共價抑制劑
KR20160013204A (ko)	2013-05-30	2016-02-03	인피니티 파마슈티칼스, 인코포레이티드	Pi3 키나아제 동형단백질 조절제를 사용하는 암의 치료
WO2014194030A2 (en)	2013-05-31	2014-12-04	Immunogen, Inc.	Conjugates comprising cell-binding agents and cytotoxic agents
WO2015006555A2 (en)	2013-07-10	2015-01-15	Sutro Biopharma, Inc.	Antibodies comprising multiple site-specific non-natural amino acid residues, methods of their preparation and methods of their use
WO2015024016A2 (en)	2013-08-16	2015-02-19	Duke University	2-piperidinyl substituted n,3-dihydroxybutanamides
WO2015024011A2 (en)	2013-08-16	2015-02-19	Duke University	Antibacterial compounds
AU2014306451B2 (en)	2013-08-16	2019-01-17	Duke University	Substituted hydroxamic acid compounds
SI3052096T1 (en)	2013-10-03	2018-04-30	Kura Oncology, Inc.	EAQ inhibitors and application procedures
WO2015051241A1 (en)	2013-10-04	2015-04-09	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
EP3964507A1 (en)	2013-10-04	2022-03-09	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
MX380928B (es)	2013-10-10	2025-03-12	Araxes Pharma Llc	Inhibidores de kras g12c.
TWI659021B (zh)	2013-10-10	2019-05-11	亞瑞克西斯製藥公司	Ｋｒａｓｇ１２ｃ之抑制劑
WO2015054658A1 (en)	2013-10-11	2015-04-16	Sutro Biopharma, Inc.	Modified amino acids comprising tetrazine functional groups, methods of preparation, and methods of their use
US20160244452A1 (en)	2013-10-21	2016-08-25	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
UA115388C2 (uk)	2013-11-21	2017-10-25	Пфайзер Інк.	2,6-заміщені пуринові похідні та їх застосування в лікуванні проліферативних захворювань
WO2015155624A1 (en)	2014-04-10	2015-10-15	Pfizer Inc.	Dihydropyrrolopyrimidine derivatives
WO2015168079A1 (en)	2014-04-29	2015-11-05	Infinity Pharmaceuticals, Inc.	Pyrimidine or pyridine derivatives useful as pi3k inhibitors
HRP20192056T1 (hr)	2014-04-30	2020-02-21	Pfizer Inc.	Derivati diheterocikla vezani na cikloalkil
CA2949793C (en)	2014-06-19	2024-02-27	Ariad Pharmaceuticals, Inc.	Heteroaryl compounds for kinase inhibition
WO2016001789A1 (en)	2014-06-30	2016-01-07	Pfizer Inc.	Pyrimidine derivatives as pi3k inhibitors for use in the treatment of cancer
EP3177320B1 (en)	2014-07-31	2021-01-06	The Government of the United States of America as represented by the Secretary of the Department of Health and Human Services	Human monoclonal antibodies against epha4 and their use
JO3556B1 (ar)	2014-09-18	2020-07-05	Araxes Pharma Llc	علاجات مدمجة لمعالجة السرطان
US9862701B2 (en)	2014-09-25	2018-01-09	Araxes Pharma Llc	Inhibitors of KRAS G12C mutant proteins
US10011600B2 (en)	2014-09-25	2018-07-03	Araxes Pharma Llc	Methods and compositions for inhibition of Ras
WO2016097918A1 (en)	2014-12-18	2016-06-23	Pfizer Inc.	Pyrimidine and triazine derivatives and their use as axl inhibitors
CN114984016A (zh)	2015-03-13	2022-09-02	雷斯韦洛吉克斯公司	用于治疗补体相关疾病之组合物及治疗方法
AU2016245864C1 (en)	2015-04-10	2021-09-09	Araxes Pharma Llc	Substituted quinazoline compounds and methods of use thereof
ES2856880T3 (es)	2015-04-15	2021-09-28	Araxes Pharma Llc	Inhibidores tricíclicos condensados de KRAS y métodos de uso de los mismos
AU2016252609B2 (en)	2015-04-20	2022-06-30	Sumitomo Pharma Oncology, Inc.	Predicting response to alvocidib by mitochondrial profiling
CN107709344B (zh)	2015-05-01	2022-07-15	共晶制药股份有限公司	用于治疗黄病毒科病毒和癌症的核苷类似物
HUE045585T2 (hu)	2015-05-18	2020-01-28	Tolero Pharmaceuticals Inc	Megnövelt biológiai hozzáférhetõséggel rendelkezõ Alvocidib gyógyszer-elõanyagok
TWI703150B (zh)	2015-06-04	2020-09-01	美商庫拉腫瘤技術股份有限公司	用於抑制ｍｅｎｉｎ及ｍｌｌ蛋白之交互作用的方法及組合物
WO2017009751A1 (en)	2015-07-15	2017-01-19	Pfizer Inc.	Pyrimidine derivatives
US10144724B2 (en)	2015-07-22	2018-12-04	Araxes Pharma Llc	Substituted quinazoline compounds and methods of use thereof
AU2016301315C1 (en)	2015-08-03	2022-07-07	Sumitomo Pharma Oncology, Inc.	Combination therapies for treatment of cancer
CN114230571B (zh)	2015-09-14	2025-07-08	无限药品股份有限公司	异喹啉酮的固体形式、其制备方法、包含其的组合物及其使用方法
US10730867B2 (en)	2015-09-28	2020-08-04	Araxes Pharma Llc	Inhibitors of KRAS G12C mutant proteins
EP3356347A1 (en)	2015-09-28	2018-08-08	Araxes Pharma LLC	Inhibitors of kras g12c mutant proteins
US10975071B2 (en)	2015-09-28	2021-04-13	Araxes Pharma Llc	Inhibitors of KRAS G12C mutant proteins
WO2017058728A1 (en)	2015-09-28	2017-04-06	Araxes Pharma Llc	Inhibitors of kras g12c mutant proteins
WO2017058902A1 (en)	2015-09-28	2017-04-06	Araxes Pharma Llc	Inhibitors of kras g12c mutant proteins
EP3356359B1 (en)	2015-09-28	2021-10-20	Araxes Pharma LLC	Inhibitors of kras g12c mutant proteins
WO2017058768A1 (en)	2015-09-28	2017-04-06	Araxes Pharma Llc	Inhibitors of kras g12c mutant proteins
JP2018533939A (ja)	2015-10-19	2018-11-22	アラクセスファーマエルエルシー	Ｒａｓの阻害剤をスクリーニングするための方法
KR102932353B1 (ko)	2015-11-16	2026-02-27	아락세스 파마 엘엘씨	치환된 헤테로사이클릭 그룹을 포함하는 2-치환된 퀴나졸린 화합물 및 이의 사용 방법
WO2017096165A1 (en)	2015-12-03	2017-06-08	Agios Pharmaceuticals, Inc.	Mat2a inhibitors for treating mtap null cancer
WO2017100546A1 (en)	2015-12-09	2017-06-15	Araxes Pharma Llc	Methods for preparation of quinazoline derivatives
AU2017212739B2 (en)	2016-01-27	2024-03-21	Sutro Biopharma, Inc.	Anti-CD74 antibody conjugates, compositions comprising anti-CD74 antibody conjugates and methods of using anti-CD74 antibody conjugates
US10752639B2 (en)	2016-03-16	2020-08-25	Kura Oncology, Inc.	Bridged bicyclic inhibitors of menin-MLL and methods of use
WO2017161028A1 (en)	2016-03-16	2017-09-21	Kura Oncology, Inc.	Substituted inhibitors of menin-mll and methods of use
WO2017172979A1 (en)	2016-03-30	2017-10-05	Araxes Pharma Llc	Substituted quinazoline compounds and methods of use
CN109414596B (zh)	2016-05-12	2023-09-29	密歇根大学董事会	Ash1l抑制剂和用其进行治疗的方法
WO2017201302A1 (en)	2016-05-18	2017-11-23	The University Of Chicago	Btk mutation and ibrutinib resistance
US10919914B2 (en)	2016-06-08	2021-02-16	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
US10646488B2 (en)	2016-07-13	2020-05-12	Araxes Pharma Llc	Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof
CA3035081A1 (en)	2016-09-02	2018-03-08	Dana-Farber Cancer Institute, Inc.	Composition and methods of treating b cell disorders
JP2019529484A (ja)	2016-09-29	2019-10-17	アラクセスファーマエルエルシー	Ｋｒａｓｇ１２ｃ変異体タンパク質の阻害剤
US10377743B2 (en)	2016-10-07	2019-08-13	Araxes Pharma Llc	Inhibitors of RAS and methods of use thereof
WO2018094275A1 (en)	2016-11-18	2018-05-24	Tolero Pharmaceuticals, Inc.	Alvocidib prodrugs and their use as protein kinase inhibitors
WO2018098352A2 (en)	2016-11-22	2018-05-31	Jun Oishi	Targeting kras induced immune checkpoint expression
RU2632703C1 (ru) *	2016-12-12	2017-10-09	федеральное государственное автономное образовательное учреждение высшего образования "Южный федеральный университет"	Средство для ингибирования метастазирования в легких
CA3047557A1 (en)	2016-12-19	2018-06-28	Tolero Pharmaceuticals, Inc.	Profiling peptides and methods for sensitivity profiling
CR20190338A (es)	2016-12-22	2019-09-09	Amgen Inc	Inhibidores de kras g12c y métodos para su uso
WO2018140599A1 (en)	2017-01-26	2018-08-02	Araxes Pharma Llc	Benzothiophene and benzothiazole compounds and methods of use thereof
EP3573971A1 (en)	2017-01-26	2019-12-04	Araxes Pharma LLC	1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1yl)prop-2-en-1-one derivatives and similar compounds as kras g12c modulators for treating cancer
EP3573954A1 (en)	2017-01-26	2019-12-04	Araxes Pharma LLC	Fused bicyclic benzoheteroaromatic compounds and methods of use thereof
JP7327802B2 (ja)	2017-01-26	2023-08-16	アラクセスファーマエルエルシー	縮合ヘテロ－ヘテロ二環式化合物およびその使用方法
US11136308B2 (en)	2017-01-26	2021-10-05	Araxes Pharma Llc	Substituted quinazoline and quinazolinone compounds and methods of use thereof
KR102607101B1 (ko)	2017-01-26	2023-11-29	제트엘아이피 홀딩 리미티드	Cd47 항원 결합 유닛 및 그것의 사용
US20200385364A1 (en)	2017-01-26	2020-12-10	Araxes Pharma Llc	Fused n-heterocyclic compounds and methods of use thereof
CN110691779B (zh)	2017-03-24	2023-10-10	库拉肿瘤学公司	治疗血液系统恶性肿瘤和尤因肉瘤的方法
UA127968C2 (uk)	2017-05-22	2024-02-28	Емджен Інк.	Інгібітори g12c kras і способи їх застосування
WO2018218069A1 (en)	2017-05-25	2018-11-29	Araxes Pharma Llc	Quinazoline derivatives as modulators of mutant kras, hras or nras
TW201906832A (zh)	2017-05-25	2019-02-16	美商亞瑞克西斯製藥公司	用於癌症治療之化合物及其使用方法
CN110869358A (zh)	2017-05-25	2020-03-06	亚瑞克西斯制药公司	Kras的共价抑制剂
US11542248B2 (en)	2017-06-08	2023-01-03	Kura Oncology, Inc.	Methods and compositions for inhibiting the interaction of menin with MLL proteins
EP3658588A1 (en)	2017-07-26	2020-06-03	Sutro Biopharma, Inc.	Methods of using anti-cd74 antibodies and antibody conjugates in treatment of t-cell lymphoma
US10640504B2 (en)	2017-09-08	2020-05-05	Amgen Inc.	Inhibitors of KRAS G12C and methods of using the same
JP7196160B2 (ja)	2017-09-12	2022-12-26	スミトモファーマオンコロジー，インコーポレイテッド	Ｍｃｌ－１阻害剤アルボシジブを用いた、ｂｃｌ－２阻害剤に対して非感受性である癌の治療レジメン
MA50265A (fr)	2017-09-18	2020-07-29	Sutro Biopharma Inc	Conjugués anticorps-récepteur alpha anti-folate et leurs utilisations
TW201920170A (zh)	2017-09-20	2019-06-01	美商庫拉腫瘤技術股份有限公司	經取代之menin-mll 抑制劑及使用方法
US20200237766A1 (en)	2017-10-13	2020-07-30	Tolero Pharmaceuticals, Inc.	Pkm2 activators in combination with reactive oxygen species for treatment of cancer
US10632209B2 (en)	2017-11-10	2020-04-28	The Regents Of The University Of Michigan	ASH1L inhibitors and methods of treatment therewith
JP7414282B2 (ja)	2017-12-07	2024-01-16	ザリージェンツオブザユニバーシティオブミシガン	Ｎｓｄファミリー阻害物質及びそれによる治療の方法
BR112020020246A8 (pt)	2018-04-05	2022-10-18	Sumitomo Dainippon Pharma Oncology Inc	Inibidores de cinase axl e uso dos mesmos
EP3788053B1 (en)	2018-05-04	2024-07-10	Amgen Inc.	Kras g12c inhibitors and methods of using the same
MX2020010836A (es)	2018-05-04	2021-01-08	Amgen Inc	Inhibidores de kras g12c y métodos para su uso.
WO2019217691A1 (en)	2018-05-10	2019-11-14	Amgen Inc.	Kras g12c inhibitors for the treatment of cancer
WO2019232419A1 (en)	2018-06-01	2019-12-05	Amgen Inc.	Kras g12c inhibitors and methods of using the same
EP3813784B1 (en)	2018-06-07	2024-01-10	The Regents Of The University Of Michigan	Prc1 inhibitors and prc1 inhibitors for use in methods of treatment therewith
AU2019284472B2 (en)	2018-06-11	2024-05-30	Amgen Inc.	KRAS G12C inhibitors for treating cancer
JP7369719B2 (ja)	2018-06-12	2023-10-26	アムジエン・インコーポレーテツド	ＫＲａｓＧ１２Ｃ阻害剤及びそれを使用する方法
KR20210038906A (ko)	2018-07-26	2021-04-08	스미토모 다이니폰 파마 온콜로지, 인크.	비정상적 acvr1 발현과 연관된 질환을 치료하는 방법 및 그에 사용하기 위한 acvr1 억제제
BR112021001709A2 (pt)	2018-08-01	2021-05-04	Araxes Pharma Llc	compostos espiro heterocíclicos e métodos de uso dos mesmos para o tratamento de câncer
JP2022500454A (ja)	2018-09-17	2022-01-04	ストロバイオファーマインコーポレーテッド	抗葉酸受容体抗体コンジュゲートによる併用療法
AU2019364417A1 (en)	2018-10-24	2021-05-20	Araxes Pharma Llc	2-(2-acryloyl-2,6-diazaspiro[3.4]octan-6-yl)-6-(1H-indazol-4-yl)-benzonitrile derivatives and related compounds as inhibitors of G12C mutant KRAS protein for inhibiting tumor metastasis
JP7516029B2 (ja)	2018-11-16	2024-07-16	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤化合物の重要な中間体の改良合成法
JP7377679B2 (ja)	2018-11-19	2023-11-10	アムジエン・インコーポレーテツド	がん治療のためのｋｒａｓｇ１２ｃ阻害剤及び１種以上の薬学的に活性な追加の薬剤を含む併用療法
JP7454572B2 (ja)	2018-11-19	2024-03-22	アムジエン・インコーポレーテツド	Ｋｒａｓｇ１２ｃ阻害剤及びその使用方法
EP3887373A1 (en)	2018-11-29	2021-10-06	Araxes Pharma LLC	Compounds and methods of use thereof for treatment of cancer
US11034710B2 (en)	2018-12-04	2021-06-15	Sumitomo Dainippon Pharma Oncology, Inc.	CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
IL283639B2 (en)	2018-12-20	2024-06-01	Amgen Inc	Kif18a inhibitors
AU2019401495B2 (en)	2018-12-20	2025-06-26	Amgen Inc.	Heteroaryl amides useful as KIF18A inhibitors
MA54550A (fr)	2018-12-20	2022-03-30	Amgen Inc	Inhibiteurs de kif18a
AU2019404576B2 (en)	2018-12-20	2025-07-17	Amgen Inc.	Heteroaryl amides useful as KIF18A inhibitors
HUE072069T2 (hu)	2019-02-12	2025-10-28	Sumitomo Pharma America Inc	2-((1R,4R)-4-((3-(3-(trifluormetil)fenil)imidazo[1,2- b]piridazin-6-il)amino)ciklohexil)propán-2-ol sósavas sójának kristályos formája
WO2020180768A1 (en)	2019-03-01	2020-09-10	Revolution Medicines, Inc.	Bicyclic heteroaryl compounds and uses thereof
US20230096028A1 (en)	2019-03-01	2023-03-30	Revolution Medicines, Inc.	Bicyclic heterocyclyl compounds and uses thereof
JP2022525149A (ja)	2019-03-20	2022-05-11	スミトモダイニッポンファーマオンコロジー，インコーポレイテッド	ベネトクラクスが失敗した急性骨髄性白血病（ａｍｌ）の処置
AU2020245437A1 (en)	2019-03-22	2021-09-30	Sumitomo Pharma Oncology, Inc.	Compositions comprising PKM2 modulators and methods of treatment using the same
US20220362394A1 (en)	2019-05-03	2022-11-17	Sutro Biopharma, Inc.	Anti-bcma antibody conjugates
EP3738593A1 (en)	2019-05-14	2020-11-18	Amgen, Inc	Dosing of kras inhibitor for treatment of cancers
EP3972973A1 (en)	2019-05-21	2022-03-30	Amgen Inc.	Solid state forms
AU2020300619A1 (en)	2019-07-03	2022-01-27	Sumitomo Pharma Oncology, Inc.	Tyrosine kinase non-receptor 1 (TNK1) inhibitors and uses thereof
JP7699100B2 (ja)	2019-08-02	2025-06-26	アムジエン・インコーポレーテツド	Ｋｉｆ１８ａ阻害剤
AU2020325115B2 (en)	2019-08-02	2026-03-12	Amgen Inc.	Pyridine derivatives as KIF18A inhibitors
US20220289724A1 (en)	2019-08-02	2022-09-15	Amgen Inc.	Kif18a inhibitors
MX428368B (es)	2019-08-02	2025-11-13	Amgen Inc	Inhibidores de kif18a
US20220402916A1 (en)	2019-09-18	2022-12-22	Merck Sharp & Dohme Corp.	Small molecule inhibitors of kras g12c mutant
TW202126636A (zh)	2019-09-30	2021-07-16	美商阿吉歐斯製藥公司	作為ｍｅｎｉｎ抑制劑之六氫吡啶化合物
AU2020369569B2 (en)	2019-10-24	2026-06-18	Amgen Inc.	Pyridopyrimidine derivatives useful as KRAS G12C and KRAS G12D inhibitors in the treatment of cancer
MD4051678T2 (en)	2019-10-28	2026-07-31	Merck Sharp & Dohme Llc	Small molecule inhibitors of the KRAS G12C mutant
WO2021085653A1 (en)	2019-10-31	2021-05-06	Taiho Pharmaceutical Co., Ltd.	4-aminobut-2-enamide derivatives and salts thereof
CN121471132A (zh)	2019-11-04	2026-02-06	锐新医药公司	Ras抑制剂
MX2022005359A (es)	2019-11-04	2022-06-02	Revolution Medicines Inc	Inhibidores de ras.
WO2021091956A1 (en)	2019-11-04	2021-05-14	Revolution Medicines, Inc.	Ras inhibitors
PH12022551102A1 (en)	2019-11-08	2023-11-20	Revolution Medicines Inc	Bicyclic heteroaryl compounds and uses thereof
CA3161156A1 (en)	2019-11-14	2021-05-20	Amgen Inc.	Improved synthesis of kras g12c inhibitor compound
EP4700030A3 (en)	2019-11-14	2026-03-18	Amgen, Inc.	Improved synthesis of kras g12c inhibitor compound
CN114980976A (zh)	2019-11-27	2022-08-30	锐新医药公司	共价ras抑制剂及其用途
WO2021106231A1 (en)	2019-11-29	2021-06-03	Taiho Pharmaceutical Co., Ltd.	A compound having inhibitory activity against kras g12d mutation
CA3163703A1 (en)	2020-01-07	2021-07-15	Steve Kelsey	Shp2 inhibitor dosing and methods of treating cancer
CN115151533B (zh)	2020-01-10	2025-08-08	医疗免疫工程公司	Mek抑制剂及其治疗用途
WO2021155006A1 (en)	2020-01-31	2021-08-05	Les Laboratoires Servier Sas	Inhibitors of cyclin-dependent kinases and uses thereof
US20230095053A1 (en)	2020-03-03	2023-03-30	Sutro Biopharma, Inc.	Antibodies comprising site-specific glutamine tags, methods of their preparation and methods of their use
WO2021204159A1 (en)	2020-04-08	2021-10-14	Agios Pharmaceuticals, Inc.	Menin inhibitors and methods of use for treating cancer
TW202204334A (zh)	2020-04-08	2022-02-01	美商阿吉歐斯製藥公司	Menin抑制劑及治療癌症之使用方法
US12702658B2 (en)	2020-04-24	2026-08-11	Taiho Pharmaceutical Co., Ltd.	Anticancer combination therapy with N-(1-acryloyl-azetidin-3-yl)-2-((1H-indazol-3-yl)amino)methyl)-1H-imidazole-5-carboxamide inhibitor of KRAS-G12C
WO2021215544A1 (en)	2020-04-24	2021-10-28	Taiho Pharmaceutical Co., Ltd.	Kras g12d protein inhibitors
CN115916194A (zh)	2020-06-18	2023-04-04	锐新医药公司	用于延迟、预防和治疗针对ras抑制剂的获得性抗性的方法
CN116113406B (zh)	2020-07-10	2025-08-29	密歇根大学董事会	Gas41抑制剂及其使用方法
TW202216151A (zh)	2020-07-15	2022-05-01	日商大鵬藥品工業股份有限公司	含有使用於腫瘤之治療之嘧啶化合物之組合
EP4185279A4 (en)	2020-07-24	2024-05-01	Secura Bio, Inc.	TREATING CANCER WITH PI3-KINASE ISOFORM MODULATORS
EP4208261A1 (en)	2020-09-03	2023-07-12	Revolution Medicines, Inc.	Use of sos1 inhibitors to treat malignancies with shp2 mutations
IL301298A (en)	2020-09-15	2023-05-01	Revolution Medicines Inc	Indole derivatives as RAS inhibitors in cancer therapy
TW202237119A (zh)	2020-12-10	2022-10-01	美商住友製藥腫瘤公司	Ａｌｋ﹘５抑制劑和彼之用途
AU2021409816A1 (en)	2020-12-22	2023-07-06	Qilu Regor Therapeutics Inc.	Sos1 inhibitors and uses thereof
TW202309022A (zh)	2021-04-13	2023-03-01	美商努法倫特公司	用於治療具egfr突變之癌症之胺基取代雜環
CN117396231A (zh)	2021-04-30	2024-01-12	新基公司	使用抗BCMA抗体药物缀合物（ADC）与γ分泌酶抑制剂（GSI）的组合的组合疗法
IL308195A (en)	2021-05-05	2024-01-01	Revolution Medicines Inc	RAS inhibitors for cancer treatment
WO2022235866A1 (en)	2021-05-05	2022-11-10	Revolution Medicines, Inc.	Covalent ras inhibitors and uses thereof
PE20240088A1 (es)	2021-05-05	2024-01-16	Revolution Medicines Inc	Inhibidores de ras
CN117769554A (zh)	2021-05-28	2024-03-26	大鹏药品工业株式会社	Kras突变蛋白的小分子抑制剂
CA3221395A1 (en)	2021-06-10	2022-12-15	Neurelis, Inc.	Methods and compositions for treating seizure disorders in pediatric patients
AR127308A1 (es)	2021-10-08	2024-01-10	Revolution Medicines Inc	Inhibidores ras
WO2023056589A1 (en)	2021-10-08	2023-04-13	Servier Pharmaceuticals Llc	Menin inhibitors and methods of use for treating cancer
US20240294548A1 (en)	2021-10-12	2024-09-05	Peloton Therapeutics Inc.	Tricyclic sultams and sulfamides as antitumor agents
TW202340214A (zh)	2021-12-17	2023-10-16	美商健臻公司	做為shp2抑制劑之吡唑并吡𠯤化合物
EP4227307A1 (en)	2022-02-11	2023-08-16	Genzyme Corporation	Pyrazolopyrazine compounds as shp2 inhibitors
KR20240156373A (ko)	2022-03-07	2024-10-29	암젠 인크	4-메틸-2-프로판-2-일-피리딘-3-카르보니트릴의 제조 방법
WO2023172940A1 (en)	2022-03-08	2023-09-14	Revolution Medicines, Inc.	Methods for treating immune refractory lung cancer
WO2023211812A1 (en)	2022-04-25	2023-11-02	Nested Therapeutics, Inc.	Heterocyclic derivatives as mitogen-activated protein kinase (mek) inhibitors
EP4536364A1 (en)	2022-06-10	2025-04-16	Revolution Medicines, Inc.	Macrocyclic ras inhibitors
IL317782A (en)	2022-06-30	2025-02-01	Sutro Biopharma Inc	Anti-ROR1 antibodies and conjugates thereof, compositions containing anti-ROR1 antibodies or conjugates thereof, and methods for preparing and using anti-ROR1 antibodies and conjugates thereof
EP4551558A2 (en)	2022-07-08	2025-05-14	Nested Therapeutics, Inc.	Mitogen-activated protein kinase (mek) inhibitors
IL320217A (en)	2022-10-14	2025-06-01	Black Diamond Therapeutics Inc	Methods for treating cancer using isoquinoline or 6-azaquinoline derivatives
CN121487738A (zh)	2023-03-30	2026-02-06	锐新医药公司	诱导ras gtp水解的组合物和其用途
WO2024211712A1 (en)	2023-04-07	2024-10-10	Revolution Medicines, Inc.	Condensed macrocyclic compounds as ras inhibitors
CN121487951A (zh)	2023-04-07	2026-02-06	锐新医药公司	大环ras抑制剂
AU2024251341A1 (en)	2023-04-14	2025-10-16	Revolution Medicines, Inc.	Crystalline forms of a ras inhibitor
EP4695261A1 (en)	2023-04-14	2026-02-18	Revolution Medicines, Inc.	Crystalline forms of ras inhibitors, compositions containing the same, and methods of use thereof
CN121889153A (zh)	2023-04-24	2026-04-17	耐斯泰德医疗公司	作为促分裂原活化蛋白激酶(mek)抑制剂的杂环衍生物
KR20260019479A (ko)	2023-05-04	2026-02-10	레볼루션 메디슨즈, 인크.	Ras 관련 질환 또는 장애를 위한 병용 요법
CN121889155A (zh)	2023-08-07	2026-04-17	锐新医药公司	用于治疗ras蛋白相关疾病或病症的rmc-6291
KR20260042550A (ko)	2023-08-24	2026-03-31	다이호야쿠힌고교 가부시키가이샤	세다주리딘 및 아자시티딘의 고정 용량 조합물
AU2024360465A1 (en)	2023-10-12	2026-04-09	Revolution Medicines, Inc.	Macrocyclic ras inhibitors
US12540197B2 (en)	2023-10-13	2026-02-03	Sutro Biopharma, Inc.	Anti-tissue factor antibodies and antibody conjugates, compositions comprising anti-tissue factor antibodies or antibody conjugates, and methods of making and using anti-tissue factor antibodies and antibody conjugates
KR20260096846A (ko)	2023-10-20	2026-06-24	머크 샤프 앤드 돔 엘엘씨	Kras 단백질의 소분자 억제제
WO2025090905A1 (en)	2023-10-26	2025-05-01	Nested Therapeutics, Inc.	Crystalline forms of 3-[[3-fluoro-2-(methylsulfamoylamino)-4-pyridyl]methyl]-7-[(3-fluoro-2-pyridyl)oxy]-4-methyl-chromen-2-one
AU2024404879A1 (en)	2023-12-22	2026-06-25	Regor Pharmaceuticals, Inc.	Sos1 inhibitors and uses thereof
WO2025240847A1 (en)	2024-05-17	2025-11-20	Revolution Medicines, Inc.	Ras inhibitors
WO2025250825A1 (en)	2024-05-30	2025-12-04	Sutro Biopharma, Inc.	Anti-trop2 antibodies, compositions comprising anti-trop2 antibodies and methods of making and using anti-trop2 antibodies
US20250375445A1 (en)	2024-06-07	2025-12-11	Revolution Medicines, Inc.	Methods of treating a ras protein-related disease or disorder
WO2025259841A1 (en)	2024-06-13	2025-12-18	Nested Therapeutics, Inc.	Crystalline forms of 3-[[3-fluoro-2-(methylsulfamoylamino)-4-pyridyl]jmethyl]-7-[(3-fluoro-2-pyridyl)oxy]-4-methyl-chromen-2-one
WO2025265060A1 (en)	2024-06-21	2025-12-26	Revolution Medicines, Inc.	Therapeutic compositions and methods for managing treatment-related effects
WO2026006747A1 (en)	2024-06-28	2026-01-02	Revolution Medicines, Inc.	Ras inhibitors
WO2026015801A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015796A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015790A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Methods of treating a ras related disease or disorder
WO2026015825A1 (en)	2024-07-12	2026-01-15	Revolution Medicines, Inc.	Use of ras inhibitor for treating pancreatic cancer
WO2026035750A1 (en)	2024-08-05	2026-02-12	Pivot Therapeutics, Inc.	Inhibitors of akt and uses thereof
WO2026043823A2 (en)	2024-08-19	2026-02-26	Sutro Biopharma, Inc.	Antibodies comprising site-specific non-natural amino acid residues, methods of preparation and uses thereof
WO2026050446A1 (en)	2024-08-29	2026-03-05	Revolution Medicines, Inc.	Ras inhibitors
WO2026072904A2 (en)	2024-09-26	2026-04-02	Revolution Medicines, Inc.	Compositions and methods for treating lung cancer
WO2026080697A1 (en)	2024-10-09	2026-04-16	Sutro Biopharma, Inc.	Antibody conjugates with high payload to antibody ratios, compositions comprising the same, and methods of their use
WO2026090116A2 (en)	2024-10-21	2026-04-30	Revolution Medicines, Inc.	Ras inhibitors
WO2026090245A1 (en)	2024-10-22	2026-04-30	Revolution Medicines, Inc.	Use of ras inhibitors for treating cancer
US20260108528A1 (en)	2024-10-22	2026-04-23	Revolution Medicines, Inc.	Methods of treating a ras protein-related disease or disorder
WO2026106912A1 (en)	2024-11-12	2026-05-21	Revolution Medicines, Inc.	Ras inhibitors
WO2026112260A1 (en)	2024-11-21	2026-05-28	Revolution Medicines, Inc.	Ras inhibitors
WO2026122764A2 (en)	2024-12-06	2026-06-11	Revolution Medicines, Inc.	Ras inhibitors
WO2026128688A2 (en)	2024-12-13	2026-06-18	Revolution Medicines, Inc.	Ras inhibitors
WO2026161671A1 (en)	2025-01-23	2026-07-30	Merck Sharp & Dohme Llc	Small molecule inhibitors of kras proteins
WO2026161839A1 (en)	2025-01-27	2026-07-30	Revolution Medicines, Inc.	Ras inhibitors
WO2026165269A1 (en)	2025-01-29	2026-08-06	Sutro Biopharma, Inc.	Anti-b7-h3 antibodies, compositions comprising anti-b7-h3 antibodies and methods of making and using anti- b7-h3 antibodies

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5455258A (en) *	1993-01-06	1995-10-03	Ciba-Geigy Corporation	Arylsulfonamido-substituted hydroxamic acids
US5646167A (en) *	1993-01-06	1997-07-08	Ciba-Geigy Corporation	Arylsulfonamido-substituted hydroxamix acids
AU691829B2 (en) *	1993-07-16	1998-05-28	Merck & Co., Inc.	Benzoxazinone and benzopyrimidinone piperidinyl tocolytic oxytocin receptor antagonists
DK0780386T3 (da) *	1995-12-20	2003-02-03	Hoffmann La Roche	Matrixmetalloproteaseinhibitorer
US6172057B1 (en) *	1997-02-27	2001-01-09	American Cyanamid Company	N-Hydroxy-2-(alkyl, aryl, or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors
AU748998B2 (en)	1997-02-27	2002-06-13	Wyeth Holdings Corporation	N-hydroxy-2-(alkyl, aryl, or heteroaryl sulfanyl, sulfinyl or sulfonyl)-3-substituted alkyl, aryl or heteroarylamides as matrix metalloproteinase inhibitors
CA2255284A1 (en) *	1997-12-22	1999-06-22	Forschungszentrum Julich Gmbh	Unicellular or multicellular organisms for preparing riboflavin
GB9801690D0 (en) *	1998-01-27	1998-03-25	Pfizer Ltd	Therapeutic agents

1997
- 1997-12-05 GB GBGB9725782.8A patent/GB9725782D0/en not_active Ceased
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- 1998-09-10 UA UA2000053127A patent/UA52791C2/uk unknown
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- 1998-10-09 NZ NZ504421A patent/NZ504421A/en unknown
- 1998-10-09 PT PT98955494T patent/PT1036062E/pt unknown
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- 1998-10-09 DK DK98955494T patent/DK1036062T3/da active
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- 1998-10-09 JP JP2000524264A patent/JP3445242B2/ja not_active Expired - Fee Related
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- 1998-10-09 CN CN98811874A patent/CN1281433A/zh active Pending
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- 1998-12-02 DZ DZ980276A patent/DZ2666A1/xx active
- 1998-12-03 UY UY25280A patent/UY25280A1/es not_active IP Right Cessation
- 1998-12-03 AP APAP/P/1998/001412A patent/AP930A/en active
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- 1998-12-03 AR ARP980106144A patent/AR016429A1/es not_active Application Discontinuation
- 1998-12-04 ZA ZA9811112A patent/ZA9811112B/xx unknown
2000
- 2000-05-19 IS IS5503A patent/IS5503A/is unknown
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Also Published As

Publication number	Publication date
US6495568B1 (en)	2002-12-17
IL136300A0 (en)	2001-05-20
ID24626A (id)	2000-07-27
WO1999029667A1 (en)	1999-06-17
ZA9811112B (en)	2000-06-05
PA8463501A1 (es)	2000-09-29
TR200001611T2 (tr)	2000-10-23
CN1281433A (zh)	2001-01-24
ES2212373T3 (es)	2004-07-16
AU741859B2 (en)	2001-12-13
BG104506A (bg)	2001-01-31
ATE257151T1 (de)	2004-01-15
PE133999A1 (es)	2000-01-10
UY25280A1 (es)	2001-01-31
NO20002826D0 (no)	2000-06-02
JP3445242B2 (ja)	2003-09-08
PL341031A1 (en)	2001-03-26
AR016429A1 (es)	2001-07-04
EA200000481A1 (ru)	2000-12-25
EA002882B1 (ru)	2002-10-31
GB9725782D0 (en)	1998-02-04
TNSN98216A1 (fr)	2005-03-15
CZ20002037A3 (cs)	2001-09-12
DZ2666A1 (fr)	2003-03-22
CA2312935A1 (en)	1999-06-17
EP1036062B1 (en)	2004-01-02
HUP0100845A2 (hu)	2001-08-28
MA26571A1 (fr)	2004-12-20
GT199800189A (es)	2000-05-18
KR20010024688A (ko)	2001-03-26
AP9801412A0 (en)	1998-12-31
HRP20000373A2 (en)	2000-12-31
EP1036062A1 (en)	2000-09-20
DE69820906T2 (de)	2004-07-15
UY25282A1 (es)	1999-07-19
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DK1036062T3 (da)	2004-04-05
AU1230199A (en)	1999-06-28
UA52791C2 (uk)	2003-01-15
AP930A (en)	2001-01-26
SK7822000A3 (en)	2001-12-03
YU32100A (sh)	2003-02-28
CA2312935C (en)	2006-03-14
KR100372990B1 (ko)	2003-02-25
NZ504421A (en)	2002-02-01
BR9813360A (pt)	2000-10-17
NO20002826L (no)	2000-07-26
IS5503A (is)	2000-05-19
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HUP0100845A3 (en)	2002-12-28
DE69820906D1 (de)	2004-02-05

Publication	Publication Date	Title
US6495568B1 (en)	2002-12-17	Hydroxamic acid derivatives as matrix metalloprotease (MMP) inhibitors
EP0363963B1 (en)	1995-04-26	Piperidinyl benzimidazoles as antihistamines
US6610711B2 (en)	2003-08-26	4-phenylpiperidines for the treatment of pruritic dermatoses
CA2278694C (en)	2006-09-26	Sulfamide-metalloprotease inhibitors
MXPA01012450A (es)	2002-06-04	Inhibidores de metaloproteasas.
KR100234600B1 (ko)	1999-12-15	중추신경계 약제로서의 1,3-치환된 시클로알켄 및 시클로알칸
EP0623120A1 (en)	1994-11-09	Piperidineacetic acid derivatives as inhibitors of fibrinogen-dependent blood platelet aggregation
JP2004520347A (ja)	2004-07-08	Ｌｄｌ−受容体発現のインデューサーとしてのアリールピペリジンおよびピペラジン誘導体
MX2011003500A (es)	2011-05-02	Derivado de 7-piperidinoalquil-3,4-dihidroquinolona.
US20040102418A1 (en)	2004-05-27	Compounds for the treatment of inflammatory disorders
KR100694682B1 (ko)	2007-03-13	4-치환 피페리딘 유도체 불화물
EP0364123B1 (en)	1991-06-12	Muscarinic receptor antagonists
US5604242A (en)	1997-02-18	Heterocyclic chemistry
US5182399A (en)	1993-01-26	Process for preparing piperidinyl benzimidazoles
MXPA00005520A (en)	2001-07-03	Hydroxamic acid derivatives as matrix metalloprotease (mmp) inhibitors
EP1708704A2 (en)	2006-10-11	4-aryl piperidines
KR100838645B1 (ko)	2008-06-16	베타-세크리테아제 활성을 억제하는 피페리딘 화합물
US5608069A (en)	1997-03-04	1-substituted, 3-carboxylic acid piperidine derivatives