NO317576B1 - Farnesyltransferase-inhiberende quinazolinoner - Google Patents

Farnesyltransferase-inhiberende quinazolinoner Download PDF

Info

Publication number: NO317576B1
Authority: NO; Norway
Prior art keywords: formula; hydrogen; compound; 6alkyl; alkyl
Prior art date: 1997-04-25

Application number

NO19995169A

Other languages

English (en)

Norwegian (no)

Other versions

NO995169D0 (no

NO995169L (no

Inventor

Eddy Jean Edgard Freyne

Marc Gaston Venet

Patrick Rene Angibaud

Original Assignee

Janssen Pharmaceutica Nv

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.)

1997-04-25

Filing date

1999-10-22

Publication date

2004-11-15

1999-10-22 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

1999-10-22 Publication of NO995169D0 publication Critical patent/NO995169D0/no

1999-12-27 Publication of NO995169L publication Critical patent/NO995169L/no

2004-11-15 Publication of NO317576B1 publication Critical patent/NO317576B1/no

Links

230000002401 inhibitory effect Effects 0.000 title abstract description 5
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108010007508 Farnesyltranstransferase Proteins 0.000 title abstract 2
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 93
239000001257 hydrogen Substances 0.000 claims abstract description 32
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 32
239000002253 acid Substances 0.000 claims abstract description 20
150000003839 salts Chemical class 0.000 claims abstract description 15
238000002360 preparation method Methods 0.000 claims abstract description 10
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 9
239000003814 drug Substances 0.000 claims abstract description 5
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
239000001301 oxygen Substances 0.000 claims abstract description 4
229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 21
125000000217 alkyl group Chemical group 0.000 claims description 14
238000000034 method Methods 0.000 claims description 13
-1 1-methyl-1H-imidazol-5-yl Chemical group 0.000 claims description 8
238000006243 chemical reaction Methods 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 8
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125000002883 imidazolyl group Chemical group 0.000 abstract description 2
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125000004953 trihalomethyl group Chemical group 0.000 abstract 2
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
- C07D239/82—Oxygen atoms with an aryl radical attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D403/06—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 linked by a carbon chain containing only aliphatic 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
- C07D405/04—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 directly linked by a ring-member-to-ring-member bond

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Medicines Containing Plant Substances (AREA)
Silver Salt Photography Or Processing Solution Therefor (AREA)
Cosmetics (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)

NO19995169A 1997-04-25 1999-10-22 Farnesyltransferase-inhiberende quinazolinoner NO317576B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP97201259		1997-04-25
PCT/EP1998/002357 WO1998049157A1 (en)	1997-04-25	1998-04-17	Farnesyltransferase inhibiting quinazolinones

Publications (3)

Publication Number	Publication Date
NO995169D0 NO995169D0 (no)	1999-10-22
NO995169L NO995169L (no)	1999-12-27
NO317576B1 true NO317576B1 (no)	2004-11-15

Family

ID=8228267

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19995169A NO317576B1 (no)	1997-04-25	1999-10-22	Farnesyltransferase-inhiberende quinazolinoner

Country Status (22)

Country	Link
US (2)	US6177432B1 (pt)
EP (1)	EP0977750B1 (pt)
JP (1)	JP4308919B2 (pt)
KR (1)	KR100520401B1 (pt)
CN (1)	CN1094937C (pt)
AT (1)	ATE366250T1 (pt)
AU (1)	AU738628B2 (pt)
BR (1)	BR9809398A (pt)
CA (1)	CA2288140C (pt)
CZ (1)	CZ296959B6 (pt)
DE (1)	DE69838025T2 (pt)
ES (1)	ES2289783T3 (pt)
HU (1)	HUP0001122A3 (pt)
IL (1)	IL130363A (pt)
NO (1)	NO317576B1 (pt)
NZ (1)	NZ336233A (pt)
PL (1)	PL190944B1 (pt)
RU (1)	RU2205831C2 (pt)
SK (1)	SK146199A3 (pt)
TR (1)	TR199902606T2 (pt)
WO (1)	WO1998049157A1 (pt)
ZA (1)	ZA983504B (pt)

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JP4308919B2 (ja) *	1997-04-25	2009-08-05	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	ファルネシルトランスフェラーゼ阻害性キナゾリノン類
HRP20000904A2 (en)	1998-07-06	2001-12-31	Janssen Pharmaceutica Nv	Farnesyl protein transferase inhibitors for treating arthropathies
US6316436B1 (en)	1998-12-08	2001-11-13	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
WO2000034437A2 (en)	1998-12-08	2000-06-15	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
ES2200591T3 (es) *	1998-12-23	2004-03-01	Janssen Pharmaceutica N.V.	Derivados de 1,2-quinolina anelados.
KR20010077400A (ko) *	2000-02-02	2001-08-17	성재갑	에프타아제 저해제인 엘비42908과 타(他) 항암제와의조합에 의한 항암치료제
US20030027839A1 (en) *	2000-02-04	2003-02-06	Palmer Peter Albert	Farnesyl protein transferase inhiitors for treating breast cancer
CA2397558A1 (en)	2000-02-24	2001-08-30	Janssen Pharmaceutica N.V.	Dosing regimen
JP2003525237A (ja) *	2000-02-29	2003-08-26	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	抗腫瘍性アントラサイクリン誘導体とのファルネシルタンパク質トランスフェラーゼ阻害剤組み合わせ剤
US20030125326A1 (en) *	2000-02-29	2003-07-03	Rybak Mary Ellen Margaret	Farnesyl protein transferase inhibitor combinations
WO2001064199A2 (en) *	2000-02-29	2001-09-07	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations with taxane compounds
US20030027808A1 (en) *	2000-02-29	2003-02-06	Palmer Peter Albert	Farnesyl protein transferase inhibitor combinations with platinum compounds
CA2397446A1 (en) *	2000-02-29	2001-09-07	Janssen Pharmaceutica Inc.	Combinations of a farnesyl protein transferase inhibitor with nitrogen mustard or nitrosourea alkylating agents
AU2001254672A1 (en) *	2000-02-29	2001-09-12	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations with an her2 antibody
JP2003525236A (ja) *	2000-02-29	2003-08-26	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	ビンカアルカロイドとのファルネシルタンパク質トランスフェラーゼ阻害剤の組み合わせ剤
US20030212008A1 (en) *	2000-02-29	2003-11-13	Palmer Peter Albert	Farnesyl protein transferase inhibitor combinations with further anti-cancer agents
WO2001064194A2 (en) *	2000-02-29	2001-09-07	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations with camptothecin compounds
JP2003525235A (ja) *	2000-02-29	2003-08-26	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	抗腫瘍ヌクレオシド誘導体とのファルネシルタンパク質トランスフェラーゼ阻害剤の組み合わせ剤
EP1267871A2 (en) *	2000-02-29	2003-01-02	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations with anti-tumor podophyllotoxin derivatives
JO2361B1 (en) *	2000-06-22	2006-12-12	جانسين فارماسيوتيكا ان. في	Enaniumer 1,2-anylated quinoline inhibitor for the transporter - farnesyl
EP1322644A1 (en) *	2000-09-25	2003-07-02	Janssen Pharmaceutica N.V.	Farnesyl transferase inhibiting 6-heterocyclylmethyl quinolinone derivatives
JP4974437B2 (ja) *	2000-09-25	2012-07-11	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	ファルネシルトランスフェラーゼを阻害する６−［（置換フェニル）メチル］−キノリンおよびキナゾリン誘導体
AU2001293826A1 (en) *	2000-09-25	2002-04-02	Janssen Pharmaceutica N.V.	Farnesyl transferase inhibiting quinoline and quinazoline derivatives as farnesyl transferase inhibitors
US7196094B2 (en)	2000-09-25	2007-03-27	Janssen Pharmaceutica, N.V.	Farnesyl transferase inhibiting 6-heterocyclylmethyl quinoline and quinazoline derivatives
JP4348080B2 (ja)	2000-11-21	2009-10-21	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	ファルネシルトランスフェラーゼを阻害するベンゾ複素環誘導体
AU2002218311A1 (en) *	2000-11-28	2002-06-11	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitors for the treatment of inflammatory bowel disease
ES2260316T3 (es) *	2000-12-27	2006-11-01	Janssen Pharmaceutica N.V.	Derivados de quinazolina y quinolina 4-sustituidos que inhiben la farnesil transferasa.
DE60230017D1 (de) *	2001-02-15	2009-01-08	Janssen Pharmaceutica Nv	Farnesyl-protein-transferase hemmer in kombination mit antiöstrogenen
CA2438421C (en) *	2001-03-12	2010-05-18	Janssen Pharmaceutica N.V.	Process for the preparation of imidazole compounds
US20020177575A1 (en) *	2001-05-04	2002-11-28	Ward Wakeland	Identification of farnesyl-protein transferase as a target for systemic lupus erythematosus therapies
CA2469275C (en)	2001-12-19	2011-09-06	Janssen Pharmaceutica N.V.	1,8-annelated quinoline derivatives substituted with carbon-linked triazoles as farnesyl transferase inhibitors
FR2837201A1 (fr) *	2002-03-18	2003-09-19	Servier Lab	Nouveaux composes derives de la quinazoline, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
AU2003223970B2 (en)	2002-03-22	2008-03-06	Janssen Pharmaceutica N.V.	Benzylimidazolyl substituted 2-quinoline and quinazoline derivatives for use as farnesyl transferase inhibitors
EP1497295B1 (en)	2002-04-15	2006-08-16	Janssen Pharmaceutica N.V.	Farnesyl transferase inhibiting tricyclic quinazoline derivatives substituted with carbon-linked imidazoles or triazoles
US20030125268A1 (en) *	2002-08-28	2003-07-03	Rybak Mary Ellen Margaret	Farnesyl protein transferase inhibitor combinations with anti-tumor anthracycline derivatives
US20050272722A1 (en) *	2004-03-18	2005-12-08	The Brigham And Women's Hospital, Inc.	Methods for the treatment of synucleinopathies
WO2005089518A2 (en) *	2004-03-18	2005-09-29	The Brigham And Women's Hospital, Inc.	Uch-l1 expression and cancer therapy
US20070293539A1 (en) *	2004-03-18	2007-12-20	Lansbury Peter T	Methods for the treatment of synucleinopathies
WO2005089504A2 (en) *	2004-03-18	2005-09-29	The Brigham And Women's Hospital, Inc.	Methods for the treatment of synucleinopathies
WO2005089502A2 (en) *	2004-03-18	2005-09-29	The Brigham And Women's Hospital, Inc.	Methods for the treatment of synucleinopathies
WO2005089496A2 (en) *	2004-03-18	2005-09-29	The Brigham And Women's Hospital, Inc.	Methods for the treatment of synucleinopathies
EP1655289A1 (en) *	2004-11-04	2006-05-10	Embl	Quinazoline derivatives, process for their preparation, their use as antimitotics and pharmaceutical compositions comprising said derivatives
RS52741B (sr)	2004-11-05	2013-08-30	Janssen Pharmaceutica N.V.	Terapeutska upotreba inhibitora farneziltransferaze i postupci praćenja njihove efikasnosti
US20060194821A1 (en) *	2005-02-18	2006-08-31	The Brigham And Women's Hospital, Inc.	Compounds inhibiting the aggregation of superoxide dismutase-1
TW200716204A (en)	2005-04-19	2007-05-01	Smithkline Beecham Cork Ltd	Pharmaceutical composition
US20060281788A1 (en)	2005-06-10	2006-12-14	Baumann Christian A	Synergistic modulation of flt3 kinase using a flt3 inhibitor and a farnesyl transferase inhibitor
EP2545919A1 (en)	2005-12-23	2013-01-16	Link Medicine Corporation	Treatment of synucleinopathies
KR101367646B1 (ko)	2006-04-20	2014-02-27	얀센 파마슈티카 엔.브이.	Ｃ-ｆｍｓ 키나제의 저해제
PL2021335T3 (pl)	2006-04-20	2011-10-31	Janssen Pharmaceutica Nv	Związki heterocykliczne jako inhibitory kinazy C-FMS
US8697716B2 (en)	2006-04-20	2014-04-15	Janssen Pharmaceutica Nv	Method of inhibiting C-KIT kinase
RU2009113612A (ru)	2006-09-11	2010-10-20	Н.В. Органон (Nl)	Ацетамидные производные хиназолинона и изохинолинона
JO3240B1 (ar)	2007-10-17	2018-03-08	Janssen Pharmaceutica Nv	c-fms مثبطات كيناز
US7932036B1 (en)	2008-03-12	2011-04-26	Veridex, Llc	Methods of determining acute myeloid leukemia response to treatment with farnesyltransferase
US8232402B2 (en) *	2008-03-12	2012-07-31	Link Medicine Corporation	Quinolinone farnesyl transferase inhibitors for the treatment of synucleinopathies and other indications
US20100331363A1 (en) *	2008-11-13	2010-12-30	Link Medicine Corporation	Treatment of mitochondrial disorders using a farnesyl transferase inhibitor
JP2012508768A (ja) *	2008-11-13	2012-04-12	リンク・メディスン・コーポレーション	アザキノリノン誘導体及びその使用
US20110060005A1 (en) *	2008-11-13	2011-03-10	Link Medicine Corporation	Treatment of mitochondrial disorders using a farnesyl transferase inhibitor
US8431576B2 (en)	2009-06-25	2013-04-30	Alkermes Pharma Ireland Limited	Heterocyclic compounds for the treatment of neurological and psychological disorders
AU2011282614B2 (en)	2010-07-28	2015-11-26	Janssen Pharmaceutica Nv	Methods of determining Acute Myeloid Leukemia response to treatment with farnesyltransferase inhibitors
AU2013299922B2 (en)	2012-08-07	2018-06-21	Janssen Pharmaceutica Nv	Process for the preparation of heterocyclic ester derivatives
JOP20180012A1 (ar)	2012-08-07	2019-01-30	Janssen Pharmaceutica Nv	عملية السلفنة باستخدام نونافلوروبوتانيسولفونيل فلوريد
CN103275085B (zh) *	2013-05-30	2015-04-08	温州大学	一种喹唑啉并喹唑啉酮化合物及其合成方法和用途
TWI621437B (zh) *	2015-08-17	2018-04-21	庫拉腫瘤技術股份有限公司	以法呢基轉移酶（farnesyltransferase）抑制劑治療癌症病患之方法
LT3534885T (lt)	2016-11-03	2021-07-12	Kura Oncology, Inc.	Farneziltransferazės inhibitoriai, skirti naudoti vėžio gydymui
WO2019113269A1 (en)	2017-12-08	2019-06-13	Kura Oncology, Inc.	Methods of treating cancer patients with farnesyltransferase inhibitors
CA3092335A1 (en)	2018-03-05	2019-09-12	Alkermes Pharma Ireland Limited	Aripiprazole dosing strategy
US20220143006A1 (en)	2019-03-15	2022-05-12	Kura Oncology, Inc.	Methods of treating cancer with farnesyltransferase inhibitors

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2002864C (en) *	1988-11-29	1999-11-16	Eddy J. E. Freyne	(1h-azol-1-ylmethyl) substituted quinoline, quinazoline or quinoxaline derivatives
US5430148A (en) *	1992-03-31	1995-07-04	Agouron Pharmaceuticals, Inc.	Antiproliferative quinazolines
CA2146126A1 (en) *	1992-10-07	1994-04-14	Kenji Irie	Pharmaceutical compositions for inhibiting the formation of tumor necrosis factor
TW321649B (pt) *	1994-11-12	1997-12-01	Zeneca Ltd
JP4308919B2 (ja) *	1997-04-25	2009-08-05	ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ	ファルネシルトランスフェラーゼ阻害性キナゾリノン類

1998
- 1998-04-17 JP JP54656198A patent/JP4308919B2/ja not_active Expired - Lifetime
- 1998-04-17 PL PL336468A patent/PL190944B1/pl unknown
- 1998-04-17 AU AU76460/98A patent/AU738628B2/en not_active Expired
- 1998-04-17 DE DE69838025T patent/DE69838025T2/de not_active Expired - Lifetime
- 1998-04-17 SK SK1461-99A patent/SK146199A3/sk unknown
- 1998-04-17 US US09/403,705 patent/US6177432B1/en not_active Expired - Lifetime
- 1998-04-17 TR TR1999/02606T patent/TR199902606T2/xx unknown
- 1998-04-17 RU RU99124815/04A patent/RU2205831C2/ru active
- 1998-04-17 ES ES98924161T patent/ES2289783T3/es not_active Expired - Lifetime
- 1998-04-17 WO PCT/EP1998/002357 patent/WO1998049157A1/en not_active Ceased
- 1998-04-17 CZ CZ0371799A patent/CZ296959B6/cs not_active IP Right Cessation
- 1998-04-17 CA CA002288140A patent/CA2288140C/en not_active Expired - Lifetime
- 1998-04-17 HU HU0001122A patent/HUP0001122A3/hu unknown
- 1998-04-17 AT AT98924161T patent/ATE366250T1/de not_active IP Right Cessation
- 1998-04-17 BR BR9809398-3A patent/BR9809398A/pt not_active Application Discontinuation
- 1998-04-17 EP EP98924161A patent/EP0977750B1/en not_active Expired - Lifetime
- 1998-04-17 IL IL13036398A patent/IL130363A/en not_active IP Right Cessation
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- 1998-04-17 KR KR10-1999-7005507A patent/KR100520401B1/ko not_active Expired - Fee Related
- 1998-04-24 ZA ZA9803504A patent/ZA983504B/xx unknown
1999
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Also Published As

Publication number	Publication date
JP4308919B2 (ja)	2009-08-05
AU738628B2 (en)	2001-09-20
KR20000069560A (ko)	2000-11-25
TR199902606T2 (xx)	2000-07-21
WO1998049157A1 (en)	1998-11-05
ATE366250T1 (de)	2007-07-15
DE69838025D1 (de)	2007-08-16
HUP0001122A3 (en)	2002-03-28
BR9809398A (pt)	2000-06-13
NO995169D0 (no)	1999-10-22
PL336468A1 (en)	2000-06-19
CA2288140C (en)	2007-04-03
US6358961B1 (en)	2002-03-19
EP0977750B1 (en)	2007-07-04
EP0977750A1 (en)	2000-02-09
NZ336233A (en)	2001-01-26
CN1094937C (zh)	2002-11-27
US6177432B1 (en)	2001-01-23
CZ296959B6 (cs)	2006-08-16
AU7646098A (en)	1998-11-24
JP2001522364A (ja)	2001-11-13
CZ371799A3 (cs)	2000-02-16
NO995169L (no)	1999-12-27
KR100520401B1 (ko)	2005-10-12
ZA983504B (en)	1999-10-25
ES2289783T3 (es)	2008-02-01
CA2288140A1 (en)	1998-11-05
PL190944B1 (pl)	2006-02-28
SK146199A3 (en)	2000-06-12
HUP0001122A2 (hu)	2001-04-28
DE69838025T2 (de)	2008-05-08
RU2205831C2 (ru)	2003-06-10
IL130363A0 (en)	2000-06-01
CN1252800A (zh)	2000-05-10
IL130363A (en)	2002-08-14

Publication	Publication Date	Title
NO317576B1 (no)	2004-11-15	Farnesyltransferase-inhiberende quinazolinoner
US6187786B1 (en)	2001-02-13	Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with N- or C-linked imidazoles
EP1322650B1 (en)	2008-09-24	Farnesyl transferase inhibiting 6-heterocyclylmethyl quinoline and quinazoline derivatives
NO318922B1 (no)	2005-05-23	1,2-annelerte kinolinderivater
US7067531B2 (en)	2006-06-27	Farnesyl transferase inhibiting 6-heterocyclylmethyl quinolinone derivatives
NO314037B1 (no)	2003-01-20	Farnesyltransferase-inhiberende 2-kinolonderivater
EP1347966B1 (en)	2006-03-08	Farnesyl transferase inhibiting 4-substituted quinoline and quinazoline derivatives
CN104936944B (zh)	2017-09-12	作为酪氨酸激酶抑制剂的吲哚满酮衍生物
AU2006237920A1 (en)	2006-10-26	Nitrogen-containing heterocyclic compound
EP1351954A1 (en)	2003-10-15	Farnesyl transferase inhibiting 4-heterocyclyl-quinoline and quinazoline derivatives
IL204127A (en)	2013-08-29	Thadiazinone derivatives
EP1339709B1 (en)	2009-06-24	Farnesyl transferase inhibiting benzoheterocyclic derivatives
MXPA99009763A (en)	2000-09-04	Farnesyltransferase inhibiting quinazolinones
HK1024689B (en)	2004-03-05	Farnesyl transferase inhibiting 1,8-annelated quinolinone derivatives substituted with n- or c-linked imidazoles