ZA200300216B - 3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta. - Google Patents

3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta. Download PDF

Info

Publication number: ZA200300216B
Authority: ZA; South Africa
Prior art keywords: gsk; compound; disease; heteroalkyl; hydrogen
Prior art date: 2000-07-27

Application number

ZA200300216A

Other languages

English (en)

Inventor

Leyi Gong

Gary Allen Peltz

Andrew Grupe

Original Assignee

Hoffmann La Roche

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.)

2000-07-27

Filing date

2003-01-08

Publication date

2004-04-08

2003-01-08 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

2004-04-08 Publication of ZA200300216B publication Critical patent/ZA200300216B/en

Links

239000003112 inhibitor Substances 0.000 title claims description 33
LKDTVSJUXXGXKE-UHFFFAOYSA-N 3-(1h-indol-2-yl)-4-phenylpyrrole-2,5-dione Chemical class C=1C2=CC=CC=C2NC=1C=1C(=O)NC(=O)C=1C1=CC=CC=C1 LKDTVSJUXXGXKE-UHFFFAOYSA-N 0.000 title description 4
108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 title description 2
102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 238
-1 cyano, nitro, amino Chemical group 0.000 claims description 227
239000000203 mixture Substances 0.000 claims description 89
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 85
229910052739 hydrogen Inorganic materials 0.000 claims description 82
239000001257 hydrogen Substances 0.000 claims description 78
238000000034 method Methods 0.000 claims description 69
125000004404 heteroalkyl group Chemical group 0.000 claims description 67
125000000217 alkyl group Chemical group 0.000 claims description 63
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 60
201000010099 disease Diseases 0.000 claims description 58
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 54
125000000623 heterocyclic group Chemical group 0.000 claims description 51
208000006673 asthma Diseases 0.000 claims description 39
150000002431 hydrogen Chemical class 0.000 claims description 38
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 33
125000000753 cycloalkyl group Chemical group 0.000 claims description 33
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
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206010020751 Hypersensitivity Diseases 0.000 claims description 21
230000007815 allergy Effects 0.000 claims description 21
229910052736 halogen Inorganic materials 0.000 claims description 21
239000000126 substance Substances 0.000 claims description 21
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208000026935 allergic disease Diseases 0.000 claims description 17
125000001153 fluoro group Chemical group F* 0.000 claims description 17
125000004475 heteroaralkyl group Chemical group 0.000 claims description 17
239000000546 pharmaceutical excipient Substances 0.000 claims description 16
125000003545 alkoxy group Chemical group 0.000 claims description 15
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
238000004519 manufacturing process Methods 0.000 claims description 15
125000001309 chloro group Chemical group Cl* 0.000 claims description 13
125000004663 dialkyl amino group Chemical group 0.000 claims description 13
230000001404 mediated effect Effects 0.000 claims description 13
125000004442 acylamino group Chemical group 0.000 claims description 12
241000124008 Mammalia Species 0.000 claims description 11
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125000001424 substituent group Chemical group 0.000 claims description 11
208000024827 Alzheimer disease Diseases 0.000 claims description 9
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206010039085 Rhinitis allergic Diseases 0.000 claims description 8
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206010028980 Neoplasm Diseases 0.000 claims description 7
208000008589 Obesity Diseases 0.000 claims description 7
201000011510 cancer Diseases 0.000 claims description 7
125000001041 indolyl group Chemical group 0.000 claims description 7
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239000002253 acid Substances 0.000 claims description 5
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IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 16
102100030627 Transcription factor 7 Human genes 0.000 description 16
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125000001316 cycloalkyl alkyl group Chemical group 0.000 description 13
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235000011152 sodium sulphate Nutrition 0.000 description 13
BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 description 11
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical group O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 11
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VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 10
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WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 9
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SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 8
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Classifications

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- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P3/04—Anorexiants; Antiobesity agents
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- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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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
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- 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
- C07D405/14—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 three or more hetero rings

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ZA200300216A 2000-07-27 2003-01-08 3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta. ZA200300216B (en)

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US22105800P	2000-07-27	2000-07-27

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ZA200300216B true ZA200300216B (en)	2004-04-08

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ZA200300216A ZA200300216B (en)	2000-07-27	2003-01-08	3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta.

Country Status (31)

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US (2)	US6479490B2 (no)
EP (1)	EP1307447B1 (no)
JP (1)	JP3984157B2 (no)
KR (1)	KR20030017655A (no)
CN (1)	CN1185229C (no)
AR (1)	AR033989A1 (no)
AT (1)	ATE284885T1 (no)
AU (1)	AU2001293702A1 (no)
BR (1)	BR0112965A (no)
CA (1)	CA2417277A1 (no)
CZ (1)	CZ2003555A3 (no)
DE (1)	DE60107857T2 (no)
EC (1)	ECSP034452A (no)
ES (1)	ES2233691T3 (no)
GT (1)	GT200100151A (no)
HR (1)	HRP20030030A2 (no)
HU (1)	HUP0301431A2 (no)
IL (1)	IL153851A0 (no)
JO (1)	JO2293B1 (no)
MA (1)	MA26936A1 (no)
MX (1)	MXPA03000695A (no)
NO (1)	NO20030328L (no)
NZ (1)	NZ523462A (no)
PA (1)	PA8523001A1 (no)
PE (1)	PE20020338A1 (no)
PL (1)	PL366701A1 (no)
RU (1)	RU2003104796A (no)
UY (1)	UY26857A1 (no)
WO (1)	WO2002010158A2 (no)
YU (1)	YU4403A (no)
ZA (1)	ZA200300216B (no)

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JP2009536669A (ja)	2006-05-09	2009-10-15	ブレインセルス，インコーポレイティド	アンジオテンシン調節による神経新生
WO2008077138A1 (en)	2006-12-19	2008-06-26	The Board Of Trustees Of The University Of Illinois	3-benzofuranyl-4-indolyl maleimides as potent gsk3 inhibitors for neurogenerative disorders
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EP2474541A1 (en)	2010-12-23	2012-07-11	Johannes- Gutenberg-Universität Mainz	Conjugated 3-(indolyl)- and 3-(azaindolyl)-4-arylmaleimide compounds and their use in tumor treatment
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2001
- 2001-07-18 KR KR10-2003-7001111A patent/KR20030017655A/ko not_active Ceased
- 2001-07-18 AU AU2001293702A patent/AU2001293702A1/en not_active Abandoned
- 2001-07-18 PL PL01366701A patent/PL366701A1/xx not_active Application Discontinuation
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- 2001-07-18 HU HU0301431A patent/HUP0301431A2/hu unknown
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- 2001-07-27 US US09/916,706 patent/US6479490B2/en not_active Expired - Fee Related
2002
- 2002-05-06 US US10/139,410 patent/US20020188018A1/en not_active Abandoned
2003
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- 2003-01-22 NO NO20030328A patent/NO20030328L/no not_active Application Discontinuation
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Also Published As

Publication number	Publication date
HRP20030030A2 (en)	2005-02-28
KR20030017655A (ko)	2003-03-03
US6479490B2 (en)	2002-11-12
AR033989A1 (es)	2004-01-21
UY26857A1 (es)	2002-01-31
US20020052397A1 (en)	2002-05-02
EP1307447B1 (en)	2004-12-15
PL366701A1 (en)	2005-02-07
YU4403A (sh)	2006-05-25
JP3984157B2 (ja)	2007-10-03
JP2004505078A (ja)	2004-02-19
ECSP034452A (es)	2003-03-10
CN1444581A (zh)	2003-09-24
WO2002010158A3 (en)	2002-05-16
HUP0301431A2 (hu)	2003-08-28
PE20020338A1 (es)	2002-04-23
MXPA03000695A (es)	2003-06-04
GT200100151A (es)	2002-05-23
IL153851A0 (en)	2003-07-31
NO20030328D0 (no)	2003-01-22
ATE284885T1 (de)	2005-01-15
CN1185229C (zh)	2005-01-19
AU2001293702A1 (en)	2002-02-13
BR0112965A (pt)	2003-07-08
DE60107857T2 (de)	2005-12-08
CZ2003555A3 (en)	2004-03-17
EP1307447A2 (en)	2003-05-07
HK1058670A1 (en)	2004-05-28
US20020188018A1 (en)	2002-12-12
DE60107857D1 (de)	2005-01-20
MA26936A1 (fr)	2004-12-20
CA2417277A1 (en)	2002-02-07
PA8523001A1 (es)	2002-10-24
WO2002010158A2 (en)	2002-02-07
NZ523462A (en)	2004-09-24
RU2003104796A (ru)	2004-08-20
ES2233691T3 (es)	2005-06-16
JO2293B1 (en)	2005-09-12
NO20030328L (no)	2003-01-22

Publication	Publication Date	Title
ZA200300216B (en)	2004-04-08	3-indolyl-4-phenyl-1H-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta.
CN105492008B (zh)	2020-11-27	用于抑制fasn的化合物及组合物
AP715A (en)	1998-12-30	Quinoline and quinazoline compounds useful in therapy.
US7625889B2 (en)	2009-12-01	Substituted bis aryl and heteroaryl compounds as selective 5HT2A antagonists
CA2670422C (en)	2011-09-06	Spiroketone acetyl-coa carboxylase inhibitors
EP0464558B1 (en)	1994-12-28	Antimigraine alkoxypyrimidine derivatives
JP2002536360A (ja)	2002-10-29	インドール誘導体およびそのｍｃｐ−１受容体拮抗剤としての使用
JP2002536362A (ja)	2002-10-29	抗炎症剤としてのインドール誘導体
JPH09507066A (ja)	1997-07-15	プロテインキナーゼｃ阻害剤
EP1689739B1 (en)	2016-03-30	Azole-based kinase inhibitors
WO2023086350A1 (en)	2023-05-19	Alkyne-containing antiviral agents
HU193754B (en)	1987-11-30	Process for preparing pyrrolo-benzimidazoles
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HU200337B (en)	1990-05-28	Process for producing substituted 6-phenyldihydro-3/2h/-pyridazinone derivatives and pharmaceutical compositions comprising such compounds
TW200403233A (en)	2004-03-01	Chemical compounds
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AU707770B2 (en)	1999-07-22	Antimigraine 1,2,5-thiadiazole derivatives of indolylalkyl- pyridinyl and pyrimidinylpiperazines
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KR20020064374A (ko)	2002-08-07	Ｍｃｐ-1 수용체 길항제인 인돌 유도체
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HK40048161B (en)	2023-01-20	Substituted triazolo quinoxaline derivatives
HK1058670B (en)	2005-05-06	3-indolyl-4-phenyl-1h-pyrrole-2,5-dione derivatives as inhibitors of glycogen synthase kinase-3beta