CA2237221A1 - Protein kinase c inhibitor - Google Patents

Protein kinase c inhibitor

Info

Publication number
CA2237221A1
CA2237221A1 CA002237221A CA2237221A CA2237221A1 CA 2237221 A1 CA2237221 A1 CA 2237221A1 CA 002237221 A CA002237221 A CA 002237221A CA 2237221 A CA2237221 A CA 2237221A CA 2237221 A1 CA2237221 A1 CA 2237221A1
Authority
CA
Canada
Prior art keywords
protein kinase
inhibitor
indolylmaleimide
solvates
mammals
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002237221A
Other languages
French (fr)
Other versions
CA2237221C (en
Inventor
Gary Lowell Engel
Nagy Alphonse Farid
Margaret Mary Faul
Michael Robert Jirousek
Lori Ann Richardson
Leonard Larry Winneroski Jr.
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eli Lilly and Co
Original Assignee
Eli Lilly And Company
Gary Lowell Engel
Nagy Alphonse Farid
Margaret Mary Faul
Michael Robert Jirousek
Lori Ann Richardson
Leonard Larry Winneroski Jr.
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.)
Filing date
Publication date
Application filed by Eli Lilly And Company, Gary Lowell Engel, Nagy Alphonse Farid, Margaret Mary Faul, Michael Robert Jirousek, Lori Ann Richardson, Leonard Larry Winneroski Jr. filed Critical Eli Lilly And Company
Publication of CA2237221A1 publication Critical patent/CA2237221A1/en
Application granted granted Critical
Publication of CA2237221C publication Critical patent/CA2237221C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
    • 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
    • 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
    • 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

Abstract

This invention provides novel bis-indolylmaleimide macrocycle derivatives of formula (Ia), and solvates thereof. The invention further provides the preparation, pharmaceutical formulations and the methods of use for inhibiting Protein Kinase C in mammals.
CA002237221A 1995-11-20 1996-11-18 Protein kinase c inhibitor Expired - Fee Related CA2237221C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US697095P 1995-11-20 1995-11-20
US60/006,970 1995-11-20
PCT/US1996/018512 WO1997018809A1 (en) 1995-11-20 1996-11-18 Protein kinase c inhibitor

Publications (2)

Publication Number Publication Date
CA2237221A1 true CA2237221A1 (en) 1997-05-29
CA2237221C CA2237221C (en) 2003-03-25

Family

ID=21723527

Family Applications (1)

Application Number Title Priority Date Filing Date
CA002237221A Expired - Fee Related CA2237221C (en) 1995-11-20 1996-11-18 Protein kinase c inhibitor

Country Status (34)

Country Link
US (3) US5710145A (en)
EP (1) EP0776895B1 (en)
JP (1) JP3348859B2 (en)
KR (1) KR100304210B1 (en)
CN (1) CN1093759C (en)
AR (2) AR004336A1 (en)
AT (1) ATE172199T1 (en)
AU (1) AU711125B2 (en)
BR (1) BR9611724A (en)
CA (1) CA2237221C (en)
CO (1) CO4750823A1 (en)
CY (1) CY2103B1 (en)
CZ (1) CZ297524B6 (en)
DE (1) DE69600784T2 (en)
DK (1) DK0776895T3 (en)
EA (1) EA000967B1 (en)
EG (1) EG23871A (en)
ES (1) ES2122764T3 (en)
HU (1) HU226821B1 (en)
IL (1) IL124417A (en)
MX (1) MX9803792A (en)
MY (1) MY118068A (en)
NO (1) NO310196B1 (en)
NZ (1) NZ323571A (en)
PE (1) PE22798A1 (en)
PL (1) PL184715B1 (en)
RO (1) RO120074B1 (en)
SI (1) SI0776895T1 (en)
TR (1) TR199800759T2 (en)
TW (1) TW403754B (en)
UA (1) UA61897C2 (en)
WO (1) WO1997018809A1 (en)
YU (1) YU49315B (en)
ZA (1) ZA969646B (en)

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US6093740A (en) * 1997-04-30 2000-07-25 Eli Lilly And Company Therapeutic treatment for skin disorders
AR017200A1 (en) 1997-12-23 2001-08-22 Astrazeneca Ab INHIBITING COMPOUNDS OF PROTEIN CINASE C, PHARMACEUTICALLY ACCEPTABLE SALTS OF THE SAME, PHARMACEUTICAL FORMULATIONS THAT UNDERSTAND THEM, USE THE SAME AND PROCESS FOR THE SYNTHESIS OF SUCH COMPOUNDS
CA2319418A1 (en) * 1998-01-30 1999-08-05 Daiso Co., Ltd. Processes for preparing butanetriol derivatives
US6225301B1 (en) 1998-03-05 2001-05-01 Eli Lilly And Company Therapeutic treatment for renal dysfunction
US6291446B1 (en) * 1998-03-05 2001-09-18 Eli Lilly And Company Therapeutic treatment for cytomegalovirus infection
US6103713A (en) * 1998-03-05 2000-08-15 Eli Lilly And Company Therapeutic treatment for autoimmune diseases
US6103712A (en) * 1998-03-05 2000-08-15 Eli Lilly And Company Therapeutic treatment for asthma
DE69911935T3 (en) * 1998-03-13 2008-02-07 The University Of British Columbia, Vancouver GRANULATIMIDE DERIVATIVES FOR THE TREATMENT OF CANCER
CA2245029A1 (en) 1998-03-13 1999-09-13 University Of British Columbia Granulatimide compounds as g2 checkpoint inhibitors
SE9800835D0 (en) 1998-03-13 1998-03-13 Astra Ab New Compounds
US6706721B1 (en) 1998-04-29 2004-03-16 Osi Pharmaceuticals, Inc. N-(3-ethynylphenylamino)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine mesylate anhydrate and monohydrate
US6127401A (en) 1998-06-05 2000-10-03 Cephalon, Inc. Bridged indenopyrrolocarbazoles
TWI223598B (en) * 1998-06-22 2004-11-11 Pfizer Ireland Pharmaceuticals An intranasal pharmaceutical composition for the treatment of male erectile dysfunction or female sexual disorders, an intranasal delivery system or device and sildenafil mesylate
GB9828640D0 (en) * 1998-12-23 1999-02-17 Smithkline Beecham Plc Novel method and compounds
US6841567B1 (en) 1999-02-12 2005-01-11 Cephalon, Inc. Cyclic substituted fused pyrrolocarbazoles and isoindolones
US6492406B1 (en) 1999-05-21 2002-12-10 Astrazeneca Ab Pharmaceutically active compounds
US6284783B1 (en) 1999-06-09 2001-09-04 The Uab Research Foundation Use of bisindolylmaleimide compounds to induce Fas-mediated apoptosis
US6399780B1 (en) 1999-08-20 2002-06-04 Cephalon, Inc. Isomeric fused pyrrolocarbazoles and isoindolones
UA74803C2 (en) 1999-11-11 2006-02-15 Осі Фармасьютікалз, Інк. A stable polymorph of n-(3-ethynylphenyl)-6,7-bis(2-methoxyetoxy)-4-quinazolinamine hydrochloride, a method for producing thereof (variants) and pharmaceutical use
US7087613B2 (en) * 1999-11-11 2006-08-08 Osi Pharmaceuticals, Inc. Treating abnormal cell growth with a stable polymorph of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine hydrochloride
US6852688B2 (en) 2000-03-10 2005-02-08 University Of Florida Compositions for treating diabetic retinopathy and methods of using same
US20030224415A1 (en) * 2001-06-29 2003-12-04 Gala Design, Inc. Selection free growth of host cells containing multiple integrating vectors
US6852510B2 (en) * 2000-07-03 2005-02-08 Gala Design Inc Host cells containing multiple integrating vectors
JP4762478B2 (en) * 2000-07-03 2011-08-31 キャタレント ファーマ ソリューションズ リミテッド ライアビリティ カンパニー Expression vector
US6300106B1 (en) * 2000-11-22 2001-10-09 Ppg Industries Ohio, Inc. Method of preparing 3-[2-{(Methylsulfonyl)oxy}-ethoxy ]-4-(triphenylmethoxy)-1-butanol, methane sulfonate
US7384738B2 (en) * 2002-03-28 2008-06-10 Bremel Robert D Retrovirus-based genomic screening
US20040038304A1 (en) * 2002-03-28 2004-02-26 Gala Design, Inc. Antibody libraries
CA2484797A1 (en) * 2002-05-06 2003-11-13 Washington University Methods of treatment of glaucoma and other conditions mediated by nos-2 expression via inhibition of the egfr pathway
DE10244453A1 (en) * 2002-09-24 2004-04-01 Phenomiques Gmbh Inhibition of the protein kinase C-alpha for the treatment of diseases
US7232842B2 (en) * 2003-01-10 2007-06-19 Board Of Trustees Of The Leland Stanford Junior University Kinase inhibitors and associated pharmaceutical compositions and methods of use
WO2004111077A1 (en) 2003-06-18 2004-12-23 Tranzyme Pharma Inc. Macrocyclic antagonists of the motilin receptor
US20050152942A1 (en) * 2003-12-23 2005-07-14 Medtronic Vascular, Inc. Medical devices to treat or inhibit restenosis
US20050221429A1 (en) * 2004-01-16 2005-10-06 Cardinal Health Pts, Llc Host cells containing multiple integrating vectors comprising an amplifiable marker
NZ550340A (en) * 2004-03-17 2010-08-27 Lars Michael Larsen Prevention of retinopathy by inhibition of the visual cycle using a retinoid
DE102004019413A1 (en) * 2004-04-19 2005-11-24 Phenos Gmbh Use of substances (e.g. nucleic acids, proteins and peptides), which restrain/reduce the expression and/or activity of protein kinase C-epsilon for the treatment/prevention of e.g. circulatory and vascular diseases
WO2006071451A2 (en) * 2004-12-03 2006-07-06 The Regents Of The University Of California Compounds that prevent macrophage apoptosis and uses thereof
WO2006068988A1 (en) * 2004-12-20 2006-06-29 Eli Lilly And Company Combination therapy for vascular complications associated with hyperglycemia
US8034823B2 (en) * 2005-02-22 2011-10-11 Savvipharm Inc Method of increasing drug oral bioavailability and compositions of less toxic orotate salts
GB0504203D0 (en) * 2005-03-01 2005-04-06 Novartis Ag Organic compounds
US8158586B2 (en) * 2005-04-11 2012-04-17 Pharmagap Inc. Inhibitors of protein kinases and uses thereof
US8508369B2 (en) 2006-09-01 2013-08-13 Intermec Ip Corp. RFID tag system with block coding, such as space-time block coding
PE20091522A1 (en) * 2007-12-21 2009-10-29 Novartis Ag SOLID PHARMACEUTICAL COMPOSITION CONTAINING 3- (1.H-INDOL-3-IL) -4- [2- (4-METHYL-PIPERAZIN-1-IL) -QUINAZOLIN-4-IL] -QUINAZOLIN-4-IL] - PIRROL-2,5-DIONA
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US9265764B2 (en) * 2009-02-27 2016-02-23 Massachusetts Institute Of Technology Uses of chemicals to modulate GSK-3 signaling for treatment of bipolar disorder and other brain disorders
CN102821759A (en) 2010-03-30 2012-12-12 诺华有限公司 PKC inhibitors for the treatment of B-cell lymphoma having chronic active B-cell-receptor signalling
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WO2014174478A1 (en) 2013-04-26 2014-10-30 Novartis Ag Pharmaceutical combinations of a pkc inhibitor and a c-met receptor tyrosine kinase inhibitor
JO3589B1 (en) 2014-08-06 2020-07-05 Novartis Ag Protein kinase c inhibitors and methods of their use
US20180185259A1 (en) 2016-12-19 2018-07-05 Chromaderm, Inc. Methods of treating hyperpigmentation disorders
WO2018175302A1 (en) 2017-03-20 2018-09-27 Sienna Biopharmaceuticals, Inc. Polymer conjugates targeting c-src with reduced exposure
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US5624949A (en) * 1993-12-07 1997-04-29 Eli Lilly And Company Protein kinase C inhibitors
BR9404831A (en) * 1993-12-07 1995-08-08 Lilly Co Eli Compound, pharmaceutical formulation and process for preparing a compound

Also Published As

Publication number Publication date
BR9611724A (en) 1999-06-01
CZ297524B6 (en) 2007-01-03
CO4750823A1 (en) 1999-03-31
US5710145A (en) 1998-01-20
CY2103B1 (en) 2002-04-05
UA61897C2 (en) 2003-12-15
CA2237221C (en) 2003-03-25
HUP9903377A2 (en) 2000-02-28
IL124417A (en) 2002-11-10
AR004336A1 (en) 1998-11-04
CN1093759C (en) 2002-11-06
EA199800374A1 (en) 1998-10-29
YU60996A (en) 1999-03-04
MY118068A (en) 2004-08-30
YU49315B (en) 2005-06-10
JP3348859B2 (en) 2002-11-20
DE69600784T2 (en) 1999-04-08
NO982182D0 (en) 1998-05-13
AU711125B2 (en) 1999-10-07
TR199800759T2 (en) 2001-01-22
WO1997018809A1 (en) 1997-05-29
PE22798A1 (en) 1998-05-11
HU226821B1 (en) 2009-11-30
NO310196B1 (en) 2001-06-05
EP0776895B1 (en) 1998-10-14
US6117861A (en) 2000-09-12
KR19990067596A (en) 1999-08-25
NZ323571A (en) 1998-12-23
ES2122764T3 (en) 1998-12-16
RO120074B1 (en) 2005-08-30
JPH11500149A (en) 1999-01-06
ZA969646B (en) 1998-05-18
CN1202825A (en) 1998-12-23
AR004717A1 (en) 1999-03-10
DE69600784D1 (en) 1998-11-19
ATE172199T1 (en) 1998-10-15
AU1054897A (en) 1997-06-11
TW403754B (en) 2000-09-01
EG23871A (en) 2007-11-27
CZ150298A3 (en) 1998-12-16
PL326754A1 (en) 1998-10-26
MX9803792A (en) 1998-09-30
EA000967B1 (en) 2000-08-28
HUP9903377A3 (en) 2000-04-28
IL124417A0 (en) 1998-12-06
US6015807A (en) 2000-01-18
SI0776895T1 (en) 1999-04-30
EP0776895A1 (en) 1997-06-04
NO982182L (en) 1998-05-13
KR100304210B1 (en) 2001-11-05
DK0776895T3 (en) 1999-06-23
PL184715B1 (en) 2002-12-31

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