NO311355B1 - Indolinonforbindelser, farmasöytisk preparat samt anvendelse - Google Patents

Indolinonforbindelser, farmasöytisk preparat samt anvendelse Download PDF

Info

Publication number: NO311355B1
Authority: NO; Norway
Prior art keywords: methylene; indolinone; alkyl; stated; cells
Prior art date: 1995-06-07

Application number

NO19965377A

Other languages

English (en)

Norwegian (no)

Other versions

NO965377D0 (no

NO965377L (no

Inventor

Peng Cho Tang

Li Sun

Gerald Mcmahon

Original Assignee

Sugen Inc

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.)

1995-06-07

Filing date

1996-12-13

Publication date

2001-11-19

1996-12-13 Application filed by Sugen Inc filed Critical Sugen Inc

1996-12-13 Publication of NO965377D0 publication Critical patent/NO965377D0/no

1997-02-12 Publication of NO965377L publication Critical patent/NO965377L/no

2001-11-19 Publication of NO311355B1 publication Critical patent/NO311355B1/no

Links

239000000825 pharmaceutical preparation Substances 0.000 title claims description 25
JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical class C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 title description 22
150000001875 compounds Chemical class 0.000 claims description 164
-1 phenyl-C-L-C4-alkyl Chemical group 0.000 claims description 115
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 52
206010028980 Neoplasm Diseases 0.000 claims description 49
208000035475 disorder Diseases 0.000 claims description 36
230000019491 signal transduction Effects 0.000 claims description 35
102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 33
108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 33
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 27
201000011510 cancer Diseases 0.000 claims description 25
239000000203 mixture Substances 0.000 claims description 25
229910052736 halogen Inorganic materials 0.000 claims description 24
150000002367 halogens Chemical class 0.000 claims description 24
238000002360 preparation method Methods 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
230000002062 proliferating effect Effects 0.000 claims description 20
201000010099 disease Diseases 0.000 claims description 16
238000011282 treatment Methods 0.000 claims description 16
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 15
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 15
238000009472 formulation Methods 0.000 claims description 13
125000004953 trihalomethyl group Chemical group 0.000 claims description 12
239000000546 pharmaceutical excipient Substances 0.000 claims description 11
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 10
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 10
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 10
QMTIIBUDOBNABZ-UHFFFAOYSA-N 3-(thiophen-2-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2C1=CC1=CC=CS1 QMTIIBUDOBNABZ-UHFFFAOYSA-N 0.000 claims description 9
230000003176 fibrotic effect Effects 0.000 claims description 9
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208000030159 metabolic disease Diseases 0.000 claims description 9
210000004204 blood vessel Anatomy 0.000 claims description 8
RSEXIUPHAVGKPO-UHFFFAOYSA-N 3-[(3,4-dimethyl-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound CC1=CNC(C=C2C3=CC=CC=C3NC2=O)=C1C RSEXIUPHAVGKPO-UHFFFAOYSA-N 0.000 claims description 7
WUWDLXZGHZSWQZ-UHFFFAOYSA-N 3-[(3,5-dimethyl-1H-pyrrol-2-yl)methylidene]-1H-indol-2-one Chemical compound N1C(C)=CC(C)=C1C=C1C2=CC=CC=C2NC1=O WUWDLXZGHZSWQZ-UHFFFAOYSA-N 0.000 claims description 7
208000019425 cirrhosis of liver Diseases 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
230000001105 regulatory effect Effects 0.000 claims description 7
JZTKNVMVUVSGJF-UHFFFAOYSA-N 1,2,3,5-oxatriazole Chemical compound C=1N=NON=1 JZTKNVMVUVSGJF-UHFFFAOYSA-N 0.000 claims description 6
XLEDBLKSWOYHES-UHFFFAOYSA-N 1,2,3,5-thiatriazole Chemical compound C=1N=NSN=1 XLEDBLKSWOYHES-UHFFFAOYSA-N 0.000 claims description 6
UGUHFDPGDQDVGX-UHFFFAOYSA-N 1,2,3-thiadiazole Chemical compound C1=CSN=N1 UGUHFDPGDQDVGX-UHFFFAOYSA-N 0.000 claims description 6
BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 6
YGTAZGSLCXNBQL-UHFFFAOYSA-N 1,2,4-thiadiazole Chemical compound C=1N=CSN=1 YGTAZGSLCXNBQL-UHFFFAOYSA-N 0.000 claims description 6
UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 claims description 6
FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 claims description 6
MBIZXFATKUQOOA-UHFFFAOYSA-N 1,3,4-thiadiazole Chemical compound C1=NN=CS1 MBIZXFATKUQOOA-UHFFFAOYSA-N 0.000 claims description 6
YYOXBJRAUDWYMQ-UHFFFAOYSA-N 2-sulfonyl-3h-furan Chemical compound O=S(=O)=C1CC=CO1 YYOXBJRAUDWYMQ-UHFFFAOYSA-N 0.000 claims description 6
NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 6
125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 6
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
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WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 6
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
206010003246 arthritis Diseases 0.000 claims description 6
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
PMUJUSJUVIXDQC-UHFFFAOYSA-N ethyl 2,4-dimethyl-5-[(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(C=C2C3=CC=CC=C3NC2=O)=C1C PMUJUSJUVIXDQC-UHFFFAOYSA-N 0.000 claims description 6
JKFAIQOWCVVSKC-UHFFFAOYSA-N furazan Chemical compound C=1C=NON=1 JKFAIQOWCVVSKC-UHFFFAOYSA-N 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
230000002401 inhibitory effect Effects 0.000 claims description 6
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 6
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
CQDAMYNQINDRQC-UHFFFAOYSA-N oxatriazole Chemical compound C1=NN=NO1 CQDAMYNQINDRQC-UHFFFAOYSA-N 0.000 claims description 6
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
238000007920 subcutaneous administration Methods 0.000 claims description 6
150000003536 tetrazoles Chemical class 0.000 claims description 6
YGNGABUJMXJPIJ-UHFFFAOYSA-N thiatriazole Chemical compound C1=NN=NS1 YGNGABUJMXJPIJ-UHFFFAOYSA-N 0.000 claims description 6
QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 5
SEZFNTZQMWJIAI-UHFFFAOYSA-N 3-(1H-pyrrol-2-ylmethylidene)-1H-indol-2-one Chemical compound O=C1NC2=CC=CC=C2C1=CC1=CC=CN1 SEZFNTZQMWJIAI-UHFFFAOYSA-N 0.000 claims description 5
WTSKCANGBVHQSV-UHFFFAOYSA-N 3-[(3-methyl-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical group C1=CNC(C=C2C3=CC=CC=C3NC2=O)=C1C WTSKCANGBVHQSV-UHFFFAOYSA-N 0.000 claims description 5
PLONGIHGLJAKNF-UHFFFAOYSA-N 3-[(3-methylthiophen-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=CSC(C=C2C3=CC=CC=C3NC2=O)=C1C PLONGIHGLJAKNF-UHFFFAOYSA-N 0.000 claims description 5
CCFZIYLSHQCVQI-UHFFFAOYSA-N 3-[(4-ethyl-3,5-dimethyl-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound CCC1=C(C)NC(C=C2C3=CC=CC=C3NC2=O)=C1C CCFZIYLSHQCVQI-UHFFFAOYSA-N 0.000 claims description 5
QLHDFRHEOWTWQG-UHFFFAOYSA-N 3-[(5-chloro-3,4-dimethyl-1h-pyrrol-2-yl)methylidene]-1h-indol-2-one Chemical compound N1C(Cl)=C(C)C(C)=C1C=C1C2=CC=CC=C2NC1=O QLHDFRHEOWTWQG-UHFFFAOYSA-N 0.000 claims description 5
IHLFVHQYUBFKRU-UHFFFAOYSA-N 6-nitro-3-(1h-pyrrol-2-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC([N+](=O)[O-])=CC=C2C1=CC1=CC=CN1 IHLFVHQYUBFKRU-UHFFFAOYSA-N 0.000 claims description 5
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239000005711 Benzoic acid Substances 0.000 claims description 5
BDSOPQFHNSQSMK-UHFFFAOYSA-N ClC=1C=C2C(C(NC2=CC=1)=O)=CC1=CN=CS1 Chemical compound ClC=1C=C2C(C(NC2=CC=1)=O)=CC1=CN=CS1 BDSOPQFHNSQSMK-UHFFFAOYSA-N 0.000 claims description 5
235000010233 benzoic acid Nutrition 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
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WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 5
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230000029663 wound healing Effects 0.000 claims description 5
GXWWJQTWHQKQEJ-UHFFFAOYSA-N 3-[(1-methyl-5-nitroimidazol-2-yl)methylidene]-1h-indol-2-one Chemical compound C1=C([N+]([O-])=O)N(C)C(C=C2C3=CC=CC=C3NC2=O)=N1 GXWWJQTWHQKQEJ-UHFFFAOYSA-N 0.000 claims description 4
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XZLCDAKBNFQCMU-UHFFFAOYSA-N 3-[4-methyl-5-[(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoic acid Chemical compound OC(=O)CCC1=CNC(C=C2C3=CC=CC=C3NC2=O)=C1C XZLCDAKBNFQCMU-UHFFFAOYSA-N 0.000 claims description 4
BKVUIEOPCYWYAT-UHFFFAOYSA-N 5-chloro-3-[(5-methylthiophen-2-yl)methylidene]-1h-indol-2-one Chemical compound S1C(C)=CC=C1C=C1C2=CC(Cl)=CC=C2NC1=O BKVUIEOPCYWYAT-UHFFFAOYSA-N 0.000 claims description 4
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230000003211 malignant effect Effects 0.000 claims description 4
CNGIYKVXXNBDFW-UHFFFAOYSA-N methyl 3-[4-methyl-2-[(2-oxo-1h-indol-3-ylidene)methyl]-1h-pyrrol-3-yl]propanoate Chemical compound CC1=CNC(C=C2C3=CC=CC=C3NC2=O)=C1CCC(=O)OC CNGIYKVXXNBDFW-UHFFFAOYSA-N 0.000 claims description 4
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NO19965377A 1995-06-07 1996-12-13 Indolinonforbindelser, farmasöytisk preparat samt anvendelse NO311355B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US08/485,323 US5880141A (en)	1995-06-07	1995-06-07	Benzylidene-Z-indoline compounds for the treatment of disease
PCT/US1996/008903 WO1996040116A1 (en)	1995-06-07	1996-06-05	Indolinone compounds for the treatment of disease

Publications (3)

Publication Number	Publication Date
NO965377D0 NO965377D0 (no)	1996-12-13
NO965377L NO965377L (no)	1997-02-12
NO311355B1 true NO311355B1 (no)	2001-11-19

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NO19965377A NO311355B1 (no)	1995-06-07	1996-12-13	Indolinonforbindelser, farmasöytisk preparat samt anvendelse

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US (9)	US5880141A (de)
EP (2)	EP0769947B1 (de)
JP (2)	JP3231044B2 (de)
CN (1)	CN1268333C (de)
AR (2)	AR003088A1 (de)
AT (1)	ATE200863T1 (de)
AU (1)	AU706597C (de)
BR (1)	BR9606410A (de)
CA (1)	CA2192797C (de)
DE (2)	DE29623744U1 (de)
DK (1)	DK0769947T3 (de)
ES (1)	ES2159741T3 (de)
GR (1)	GR3036315T3 (de)
HU (1)	HU226755B1 (de)
MX (1)	MX9606401A (de)
NO (1)	NO311355B1 (de)
NZ (1)	NZ310109A (de)
PT (1)	PT769947E (de)
WO (1)	WO1996040116A1 (de)

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1995
- 1995-06-07 US US08/485,323 patent/US5880141A/en not_active Expired - Lifetime
1996
- 1996-06-05 DK DK96918093T patent/DK0769947T3/da active
- 1996-06-05 CN CNB961906162A patent/CN1268333C/zh not_active Expired - Lifetime
- 1996-06-05 EP EP96918093A patent/EP0769947B1/de not_active Expired - Lifetime
- 1996-06-05 US US08/655,226 patent/US5886020A/en not_active Expired - Lifetime
- 1996-06-05 WO PCT/US1996/008903 patent/WO1996040116A1/en not_active Ceased
- 1996-06-05 MX MX9606401A patent/MX9606401A/es unknown
- 1996-06-05 BR BR9606410A patent/BR9606410A/pt active Search and Examination
- 1996-06-05 US US08/655,225 patent/US5834504A/en not_active Expired - Lifetime
- 1996-06-05 EP EP99103667A patent/EP0934931A3/de not_active Withdrawn
- 1996-06-05 AU AU60441/96A patent/AU706597C/en not_active Expired
- 1996-06-05 US US08/655,223 patent/US5792783A/en not_active Expired - Lifetime
- 1996-06-05 DE DE29623744U patent/DE29623744U1/de not_active Expired - Lifetime
- 1996-06-05 PT PT96918093T patent/PT769947E/pt unknown
- 1996-06-05 US US08/655,224 patent/US5883116A/en not_active Expired - Lifetime
- 1996-06-05 HU HU9701694A patent/HU226755B1/hu unknown
- 1996-06-05 US US08/659,191 patent/US5883113A/en not_active Expired - Lifetime
- 1996-06-05 CA CA002192797A patent/CA2192797C/en not_active Expired - Lifetime
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- 1996-06-05 DE DE69612649T patent/DE69612649T2/de not_active Expired - Lifetime
- 1996-06-05 JP JP50136397A patent/JP3231044B2/ja not_active Expired - Fee Related
- 1996-06-05 AT AT96918093T patent/ATE200863T1/de active
- 1996-06-11 AR ARP960103100A patent/AR003088A1/es active IP Right Grant
- 1996-12-13 NO NO19965377A patent/NO311355B1/no not_active IP Right Cessation
1998
- 1998-12-15 US US09/212,494 patent/US6225335B1/en not_active Expired - Lifetime
1999
- 1999-06-07 JP JP11159567A patent/JP2000026412A/ja active Pending
2001
- 2001-01-22 US US09/765,619 patent/US6469032B2/en not_active Expired - Lifetime
- 2001-07-31 GR GR20010401166T patent/GR3036315T3/el unknown
2002
- 2002-08-26 US US10/227,550 patent/US20030176487A1/en not_active Abandoned
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Also Published As

Publication number	Publication date
HU226755B1 (en)	2009-09-28
HK1011933A1 (en)	1999-07-23
DE29623744U1 (de)	1999-09-30
US5886020A (en)	1999-03-23
BR9606410A (pt)	1997-12-30
CN1155838A (zh)	1997-07-30
US5883113A (en)	1999-03-16
CA2192797A1 (en)	1996-12-19
US20010027207A1 (en)	2001-10-04
US6469032B2 (en)	2002-10-22
JP2000026412A (ja)	2000-01-25
EP0934931A3 (de)	1999-10-20
EP0769947A4 (de)	1998-09-30
WO1996040116A1 (en)	1996-12-19
US5834504A (en)	1998-11-10
MX9606401A (es)	1998-01-31
HUP9701694A3 (en)	2004-03-01
DE69612649D1 (de)	2001-06-07
EP0769947B1 (de)	2001-05-02
AU706597B2 (en)	1999-06-17
PT769947E (pt)	2001-10-31
AU706597C (en)	2001-10-18
DK0769947T3 (da)	2001-08-13
AU6044196A (en)	1996-12-30
EP0769947A1 (de)	1997-05-02
US5883116A (en)	1999-03-16
JP3231044B2 (ja)	2001-11-19
DE69612649T2 (de)	2001-10-31
US20030176487A1 (en)	2003-09-18
AR003088A1 (es)	1998-07-08
AR037562A2 (es)	2004-11-17
HK1001121A1 (en)	1998-05-29
CA2192797C (en)	2006-05-16
ES2159741T3 (es)	2001-10-16
US6225335B1 (en)	2001-05-01
JPH10504323A (ja)	1998-04-28
NO965377D0 (no)	1996-12-13
NZ310109A (en)	1999-01-28
ATE200863T1 (de)	2001-05-15
HUP9701694A2 (hu)	1999-06-28
EP0934931A2 (de)	1999-08-11
CN1268333C (zh)	2006-08-09
US5880141A (en)	1999-03-09
NO965377L (no)	1997-02-12
US5792783A (en)	1998-08-11
GR3036315T3 (en)	2001-10-31

Publication	Publication Date	Title
NO311355B1 (no)	2001-11-19	Indolinonforbindelser, farmasöytisk preparat samt anvendelse
US5763470A (en)	1998-06-09	Benzopyran compounds and methods for their use
US6133305A (en)	2000-10-17	3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity
US6316635B1 (en)	2001-11-13	2-indolinone derivatives as modulators of protein kinase activity
US7189721B2 (en)	2007-03-13	Bicyclic protein kinase inhibitors
US6525072B1 (en)	2003-02-25	Geometrically restricted 2-indolinone derivatives as modulators of protein kinase activity
NO318083B1 (no)	2005-01-31	Pyrrolsubstituert 2-indolinon protein kinase inhibitorer
WO2000008202A2 (en)	2000-02-17	3-methylidenyl-2-indolinone modulators of protein kinase
US6649635B2 (en)	2003-11-18	Heteroarylcarboxamide compounds active against protein tyrosine kinase related disorders
US6906093B2 (en)	2005-06-14	Indolinone combinatorial libraries and related products and methods for the treatment of disease
US6569868B2 (en)	2003-05-27	2-indolinone derivatives as modulators of protein kinase activity
HK1011933B (en)	2002-01-18	Indolinone compounds for the treatment of disease

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