SK146199A3 - Farnesyltransferase inhibiting quinazolinones - Google Patents

Farnesyltransferase inhibiting quinazolinones Download PDF

Info

Publication number: SK146199A3
Authority: SK; Slovakia
Prior art keywords: alkyl; hydrogen; formula; compound; halo
Prior art date: 1997-04-25

Application number

SK1461-99A

Other languages

English (en)

Slovak (sk)

Inventor

Patrick Rene Angibaud

Marc Gaston Venet

Eddy Jean Edgard Freyne

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

1998-04-17

Publication date

2000-06-12

1998-04-17 Application filed by Janssen Pharmaceutica Nv filed Critical Janssen Pharmaceutica Nv

2000-06-12 Publication of SK146199A3 publication Critical patent/SK146199A3/sk

Links

230000002401 inhibitory effect Effects 0.000 title abstract description 5
102000007317 Farnesyltranstransferase Human genes 0.000 title abstract description 3
108010007508 Farnesyltranstransferase Proteins 0.000 title abstract description 3
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 title description 9
150000001875 compounds Chemical class 0.000 claims abstract description 112
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 76
239000001257 hydrogen Substances 0.000 claims abstract description 75
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 50
239000002253 acid Substances 0.000 claims abstract description 22
150000002431 hydrogen Chemical class 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 19
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 10
238000002360 preparation method Methods 0.000 claims abstract description 10
229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
239000001301 oxygen Substances 0.000 claims abstract description 8
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
229910052717 sulfur Chemical group 0.000 claims abstract description 4
239000011593 sulfur Chemical group 0.000 claims abstract description 4
125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 4
125000004076 pyridyl group Chemical group 0.000 claims abstract 3
125000000217 alkyl group Chemical group 0.000 claims description 107
125000005843 halogen group Chemical group 0.000 claims description 30
125000003545 alkoxy group Chemical group 0.000 claims description 28
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 25
-1 C _' Chemical group 0.000 claims description 23
238000006243 chemical reaction Methods 0.000 claims description 20
238000000034 method Methods 0.000 claims description 18
239000002585 base Substances 0.000 claims description 12
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 12
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 12
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000001424 substituent group Chemical group 0.000 claims description 6
239000003937 drug carrier Substances 0.000 claims description 5
239000013067 intermediate product Substances 0.000 claims description 5
230000009466 transformation Effects 0.000 claims description 5
239000004480 active ingredient Substances 0.000 claims description 4
150000002576 ketones Chemical class 0.000 claims description 4
238000004519 manufacturing process Methods 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 3
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125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
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239000003513 alkali Substances 0.000 claims 2
239000012458 free base Substances 0.000 claims 2
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125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
235000018906 Bauhinia malabarica Nutrition 0.000 claims 1
244000300022 Bauhinia malabarica Species 0.000 claims 1
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239000000203 mixture Substances 0.000 abstract description 77
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125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 7
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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)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (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)
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SK1461-99A 1997-04-25 1998-04-17 Farnesyltransferase inhibiting quinazolinones SK146199A3 (en)

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 (1)

Publication Number	Publication Date
SK146199A3 true SK146199A3 (en)	2000-06-12

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ID=8228267

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1461-99A SK146199A3 (en)	1997-04-25	1998-04-17	Farnesyltransferase inhibiting quinazolinones

Country Status (22)

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

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ATE366250T1 (de) *	1997-04-25	2007-07-15	Janssen Pharmaceutica Nv	Chinazolinone die farnesyltransferase hemmen
HRP20000904A2 (en)	1998-07-06	2001-12-31	Janssen Pharmaceutica Nv	Farnesyl protein transferase inhibitors for treating arthropathies
AU2478500A (en)	1998-12-08	2000-06-26	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
US6284755B1 (en)	1998-12-08	2001-09-04	Merck & Co., Inc.	Inhibitors of prenyl-protein transferase
IL143859A0 (en) *	1998-12-23	2002-04-21	Janssen Pharmaceutica Nv	1,2-annelated quinoline derivatives
KR20010077400A (ko) *	2000-02-02	2001-08-17	성재갑	에프타아제 저해제인 엘비42908과 타(他) 항암제와의조합에 의한 항암치료제
JP5491681B2 (ja) *	2000-02-04	2014-05-14	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	乳ガンの治療のためのファルネシルタンパク質トランスフェラーゼ阻害剤
EP1267848B1 (en)	2000-02-24	2007-10-17	Janssen Pharmaceutica N.V.	Dosing regimen comprising a farnesyl protein transferase inhibitor for the treatment of cancer
JP2003525255A (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	ファルネシルタンパク質トランスフェラーゼ阻害剤とさらなる抗癌剤との組み合わせ剤
EP1267929A2 (en) *	2000-02-29	2003-01-02	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations with an her2 antibody
AU2001244167A1 (en) *	2000-02-29	2001-09-12	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations with anti-tumor anthracycline derivatives
WO2001064218A2 (en) *	2000-02-29	2001-09-07	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations
JP2003525244A (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	抗腫瘍性アルキル化剤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
JP2003525246A (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	白金化合物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
US20030181473A1 (en) *	2000-02-29	2003-09-25	Palmer Peter Albert	Farnesyl protein transferase inhibitor combinations with taxane compounds
EP1261341A2 (en) *	2000-02-29	2002-12-04	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations with camptothecin compounds
US20030186925A1 (en) *	2000-02-29	2003-10-02	Palmer Peter Albert	Farnesyl protein transferase inhibitor combinations with anti-tumor nucleoside derivatives
WO2001064196A2 (en) *	2000-02-29	2001-09-07	Janssen Pharmaceutica N.V.	Farnesyl protein transferase inhibitor combinations with vinca alkaloids
JP2003525238A (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	抗腫瘍性ポドフィロトキシ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
JO2361B1 (en)	2000-06-22	2006-12-12	جانسين فارماسيوتيكا ان. في	Enaniumer 1,2-anylated quinoline inhibitor for the transporter - farnesyl
US7196094B2 (en)	2000-09-25	2007-03-27	Janssen Pharmaceutica, N.V.	Farnesyl transferase inhibiting 6-heterocyclylmethyl quinoline and quinazoline derivatives
US7067531B2 (en)	2000-09-25	2006-06-27	Angibaud Patrick Rene	Farnesyl transferase inhibiting 6-heterocyclylmethyl quinolinone derivatives
AU2001293829A1 (en) *	2000-09-25	2002-04-02	Janssen Pharmaceutica N.V.	Farnesyl transferase inhibiting 6-((substituted phenyl)methyl)-quinoline and quinazoline derivatives
US7053105B2 (en)	2000-09-25	2006-05-30	Janssen Pharmaceutica, N.V.	Farnesyl transferase inhibiting quinoline and quinazoline derivatives as farnesyl transferase inhibitors
DE60139080D1 (de)	2000-11-21	2009-08-06	Janssen Pharmaceutica Nv	Farnesyltransferase hemmende benzoheterocyclische derivate
DK1339407T3 (da) *	2000-11-28	2006-08-14	Janssen Pharmaceutica Nv	Farnesylproteintransferaseinhibitorer til behandling af inflammatorisk tarmsygdom
DE60117847T2 (de) *	2000-12-27	2006-11-16	Janssen Pharmaceutica N.V.	Farnesyltransferase hemmende, in der 4-stellung substituierte chinolin- und chinazolinderivate
DE60230017D1 (de) *	2001-02-15	2009-01-08	Janssen Pharmaceutica Nv	Farnesyl-protein-transferase hemmer in kombination mit antiöstrogenen
PL208238B1 (pl) *	2001-03-12	2011-04-29	Janssen Pharmaceutica Nv	Sposób wytwarzania 4- (3-chlorofenylo) -6- [ (4-chlorofenylo) hydroksy (1-metylo-1H-imidazol-5-ilo) metylo] -1-metylo-2 (1H) -chinolinonu
US20020177575A1 (en) *	2001-05-04	2002-11-28	Ward Wakeland	Identification of farnesyl-protein transferase as a target for systemic lupus erythematosus therapies
AU2002358677B2 (en) *	2001-12-19	2008-02-07	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
ATE364384T1 (de)	2002-03-22	2007-07-15	Janssen Pharmaceutica Nv	Benzylimidazolyl substituierte 2-chinolon und chinazolinon derivate zur verwendung als farnesyl transferase inhibitoren
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
EP1732549A4 (en) *	2004-03-18	2009-11-11	Brigham & Womens Hospital	METHOD FOR THE TREATMENT OF SYNUCLEINOPATHIES
US20070293539A1 (en) *	2004-03-18	2007-12-20	Lansbury Peter T	Methods for the treatment of synucleinopathies
CA2559221A1 (en) *	2004-03-18	2005-09-29	Brigham And Women's Hospital, Inc.	Methods for the treatment of synucleinopathies
WO2005089515A2 (en) *	2004-03-18	2005-09-29	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
EP1744751A4 (en) *	2004-03-18	2010-03-10	Brigham & Womens Hospital	METHOD 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
ME01509B (me)	2004-11-05	2014-04-20	Janssen Pharmaceutica Nv	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
JP2009521470A (ja)	2005-12-23	2009-06-04	リンクメディシンコーポレイション	シヌクレイン障害の治療
WO2007124319A1 (en)	2006-04-20	2007-11-01	Janssen Pharmaceutica N.V.	Inhibitors of c-fms kinase
AU2007240437B2 (en)	2006-04-20	2012-12-06	Janssen Pharmaceutica N.V.	Heterocyclic compounds as inhibitors of c-fms kinase
US8697716B2 (en)	2006-04-20	2014-04-15	Janssen Pharmaceutica Nv	Method of inhibiting C-KIT kinase
EP2069315B1 (en)	2006-09-11	2011-09-07	N.V. Organon	Quinazolinone and isoquinolinone acetamide derivatives
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
WO2009151683A2 (en) *	2008-03-12	2009-12-17	Link Medicine Corporation	Quinolinone farnesyl transferase inhibitors for the treatment of synucleinopathies and other indications
US20110060005A1 (en) *	2008-11-13	2011-03-10	Link Medicine Corporation	Treatment of mitochondrial disorders using a farnesyl transferase inhibitor
US20100331363A1 (en) *	2008-11-13	2010-12-30	Link Medicine Corporation	Treatment of mitochondrial disorders using a farnesyl transferase inhibitor
NZ593090A (en) *	2008-11-13	2013-06-28	Link Medicine Corp	Azaquinolinone derivatives and uses thereof
PT2445502T (pt) *	2009-06-25	2017-09-22	Alkermes Pharma Ireland Ltd	Compostos heterocíclicos para o tratamento de distúrbios neurológicos e psicológicos
AU2011282614B2 (en)	2010-07-28	2015-11-26	Janssen Pharmaceutica Nv	Methods of determining Acute Myeloid Leukemia response to treatment with farnesyltransferase inhibitors
JOP20180012A1 (ar)	2012-08-07	2019-01-30	Janssen Pharmaceutica Nv	عملية السلفنة باستخدام نونافلوروبوتانيسولفونيل فلوريد
EP2882757B1 (en)	2012-08-07	2016-10-05	Janssen Pharmaceutica, N.V.	Process for the preparation of heterocyclic ester derivatives
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
PT3385395T (pt)	2015-08-17	2020-05-06	Kura Oncology Inc	Métodos de tratamento de doentes com cancro usando inibidores da farnesiltransferase
US11124839B2 (en)	2016-11-03	2021-09-21	Kura Oncology, Inc.	Methods of treating cancer patients with farnesyltransferase inhibitors
WO2019113269A1 (en)	2017-12-08	2019-06-13	Kura Oncology, Inc.	Methods of treating cancer patients with farnesyltransferase inhibitors
AU2019230014B2 (en)	2018-03-05	2024-11-28	Alkermes Pharma Ireland Limited	Aripiprazole dosing strategy
WO2020190604A1 (en)	2019-03-15	2020-09-24	Kura Oncology, Inc.	Methods of treating cancer patients 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
US5646154A (en) *	1992-10-07	1997-07-08	Sumitomo Pharmaceuticals Co., Ltd.	Pharmaceutical compositions for inhibiting the formation of tumor necrosis factor
TW321649B (no) *	1994-11-12	1997-12-01	Zeneca Ltd
ATE366250T1 (de) *	1997-04-25	2007-07-15	Janssen Pharmaceutica Nv	Chinazolinone die farnesyltransferase hemmen

1998
- 1998-04-17 AT AT98924161T patent/ATE366250T1/de not_active IP Right Cessation
- 1998-04-17 KR KR10-1999-7005507A patent/KR100520401B1/ko not_active Expired - Fee Related
- 1998-04-17 SK SK1461-99A patent/SK146199A3/sk unknown
- 1998-04-17 EP EP98924161A patent/EP0977750B1/en not_active Expired - Lifetime
- 1998-04-17 US US09/403,705 patent/US6177432B1/en not_active Expired - Lifetime
- 1998-04-17 WO PCT/EP1998/002357 patent/WO1998049157A1/en not_active Ceased
- 1998-04-17 BR BR9809398-3A patent/BR9809398A/pt not_active Application Discontinuation
- 1998-04-17 CN CN98804366A patent/CN1094937C/zh not_active Expired - Lifetime
- 1998-04-17 CZ CZ0371799A patent/CZ296959B6/cs not_active IP Right Cessation
- 1998-04-17 DE DE69838025T patent/DE69838025T2/de not_active Expired - Lifetime
- 1998-04-17 PL PL336468A patent/PL190944B1/pl unknown
- 1998-04-17 ES ES98924161T patent/ES2289783T3/es not_active Expired - Lifetime
- 1998-04-17 CA CA002288140A patent/CA2288140C/en not_active Expired - Lifetime
- 1998-04-17 AU AU76460/98A patent/AU738628B2/en not_active Expired
- 1998-04-17 JP JP54656198A patent/JP4308919B2/ja not_active Expired - Lifetime
- 1998-04-17 TR TR1999/02606T patent/TR199902606T2/xx unknown
- 1998-04-17 IL IL13036398A patent/IL130363A/en not_active IP Right Cessation
- 1998-04-17 HU HU0001122A patent/HUP0001122A3/hu unknown
- 1998-04-17 RU RU99124815/04A patent/RU2205831C2/ru active
- 1998-04-17 NZ NZ336233A patent/NZ336233A/xx unknown
- 1998-04-24 ZA ZA9803504A patent/ZA983504B/xx unknown
1999
- 1999-10-22 NO NO19995169A patent/NO317576B1/no unknown
2000
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Also Published As

Publication number	Publication date
ES2289783T3 (es)	2008-02-01
EP0977750B1 (en)	2007-07-04
DE69838025D1 (de)	2007-08-16
AU7646098A (en)	1998-11-24
US6177432B1 (en)	2001-01-23
IL130363A (en)	2002-08-14
EP0977750A1 (en)	2000-02-09
HUP0001122A3 (en)	2002-03-28
AU738628B2 (en)	2001-09-20
CA2288140C (en)	2007-04-03
CZ296959B6 (cs)	2006-08-16
CN1252800A (zh)	2000-05-10
BR9809398A (pt)	2000-06-13
WO1998049157A1 (en)	1998-11-05
RU2205831C2 (ru)	2003-06-10
KR100520401B1 (ko)	2005-10-12
NO995169L (no)	1999-12-27
JP2001522364A (ja)	2001-11-13
IL130363A0 (en)	2000-06-01
CN1094937C (zh)	2002-11-27
JP4308919B2 (ja)	2009-08-05
PL336468A1 (en)	2000-06-19
DE69838025T2 (de)	2008-05-08
HUP0001122A2 (hu)	2001-04-28
TR199902606T2 (xx)	2000-07-21
ATE366250T1 (de)	2007-07-15
US6358961B1 (en)	2002-03-19
CA2288140A1 (en)	1998-11-05
NZ336233A (en)	2001-01-26
CZ371799A3 (cs)	2000-02-16
ZA983504B (en)	1999-10-25
PL190944B1 (pl)	2006-02-28
NO317576B1 (no)	2004-11-15
NO995169D0 (no)	1999-10-22
KR20000069560A (ko)	2000-11-25

Publication	Publication Date	Title
SK146199A3 (en)	2000-06-12	Farnesyltransferase inhibiting quinazolinones
US6444812B1 (en)	2002-09-03	Intermediate compounds in the preparation of farnnesyl 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
EP1140935B1 (en)	2003-05-14	1,2-annelated quinoline derivatives
EP1110953B1 (en)	2009-10-28	Quinazoline derivatives
EA003933B1 (ru)	2003-10-30	Способ лечения рака, фармацевтические композиции, содержащие 2-хинолоны
AU2009228945B2 (en)	2013-05-02	Quinazolinone derivatives as tubulin polymerization inhibitors
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
HK1038740B (en)	2010-02-05	Quinazoline derivatives
CZ316799A3 (cs)	2000-03-15	1,8-Anelované chinolinonové deriváty substituované N- nebo C-vázanými imidazoly inhibující farnesyl transferázu