NO326316B1 - Substituerte naftylindol-derivater, fremgangsmate for fremstilling av disse, farmasoytiske preparater inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom. - Google Patents

Substituerte naftylindol-derivater, fremgangsmate for fremstilling av disse, farmasoytiske preparater inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom. Download PDF

Info

Publication number: NO326316B1
Authority: NO; Norway
Prior art keywords: alkyl; pentyl; pharmaceutically acceptable; naphthyl; compound according
Prior art date: 2001-06-20

Application number

NO20035635A

Other languages

English (en)

Norwegian (no)

Other versions

NO20035635D0 (no

Inventor

Scott Christian Mayer

Eric Gould Gundersen

Hassan Mahmoud Elokdah

David Leroy Crandall

Original Assignee

Wyeth Corp

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.)

2001-06-20

Filing date

2003-12-17

Publication date

2008-11-10

2003-12-17 Application filed by Wyeth Corp filed Critical Wyeth Corp

2003-12-17 Publication of NO20035635D0 publication Critical patent/NO20035635D0/no

2008-11-10 Publication of NO326316B1 publication Critical patent/NO326316B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 117
238000000034 method Methods 0.000 title claims description 29
238000011282 treatment Methods 0.000 title claims description 13
239000003814 drug Substances 0.000 title claims description 9
238000004519 manufacturing process Methods 0.000 title claims description 6
238000002360 preparation method Methods 0.000 title description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 12
201000010099 disease Diseases 0.000 title description 9
XEQHAEZWPZICKJ-UHFFFAOYSA-N 2-naphthalen-1-yl-1h-indole Chemical class C1=CC=C2C(C3=CC4=CC=CC=C4N3)=CC=CC2=C1 XEQHAEZWPZICKJ-UHFFFAOYSA-N 0.000 title description 4
230000008569 process Effects 0.000 title description 3
239000008194 pharmaceutical composition Substances 0.000 title description 2
150000003839 salts Chemical class 0.000 claims description 46
125000004432 carbon atom Chemical group C* 0.000 claims description 41
229910052739 hydrogen Inorganic materials 0.000 claims description 36
239000001257 hydrogen Substances 0.000 claims description 35
125000000217 alkyl group Chemical group 0.000 claims description 29
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
229910052736 halogen Inorganic materials 0.000 claims description 16
150000002367 halogens Chemical class 0.000 claims description 16
-1 (4-tert- butyl)benzyl Chemical group 0.000 claims description 13
239000000203 mixture Substances 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
125000001072 heteroaryl group Chemical group 0.000 claims description 11
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
125000002252 acyl group Chemical group 0.000 claims description 5
239000000825 pharmaceutical preparation Substances 0.000 claims description 5
BGKSEZRVKAASPF-UHFFFAOYSA-N 1-benzyl-2-[6-[[[6-(1-benzyl-3-pentylindol-2-yl)-1-bromonaphthalen-2-yl]-(2h-tetrazol-5-yl)methoxy]-(2h-tetrazol-5-yl)methyl]-5-bromonaphthalen-2-yl]-3-pentylindole Chemical compound C=1C=CC=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2C(C=1NN=NN=1)OC(C=1C(=C2C=CC(=CC2=CC=1)C=1N(C2=CC=CC=C2C=1CCCCC)CC=1C=CC=CC=1)Br)C1=NN=NN1 BGKSEZRVKAASPF-UHFFFAOYSA-N 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
208000007536 Thrombosis Diseases 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
239000003527 fibrinolytic agent Substances 0.000 claims description 4
230000003480 fibrinolytic effect Effects 0.000 claims description 4
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 4
229910052757 nitrogen Inorganic materials 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
PCUHYTXMDYBLDH-UHFFFAOYSA-N 2-[5-bromo-6-[[[1-bromo-6-(1-methyl-3-pentylindol-2-yl)naphthalen-2-yl]-(2h-tetrazol-5-yl)methoxy]-(2h-tetrazol-5-yl)methyl]naphthalen-2-yl]-1-methyl-3-pentylindole Chemical compound CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2C(C1=NNN=N1)OC(C=1C(=C2C=CC(=CC2=CC=1)C=1N(C2=CC=CC=C2C=1CCCCC)C)Br)C=1N=NNN=1 PCUHYTXMDYBLDH-UHFFFAOYSA-N 0.000 claims description 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 3
241000124008 Mammalia Species 0.000 claims description 3
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 3
125000004429 atom Chemical group 0.000 claims description 3
PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 claims description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
PEQJBOMPGWYIRO-UHFFFAOYSA-N n-ethyl-3,4-dimethoxyaniline Chemical compound CCNC1=CC=C(OC)C(OC)=C1 PEQJBOMPGWYIRO-UHFFFAOYSA-N 0.000 claims description 3
150000003536 tetrazoles Chemical class 0.000 claims description 3
SRZKBYNNCQFTFV-UHFFFAOYSA-N 1-[(4-tert-butylphenyl)methyl]-3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]indole Chemical compound C=1C=C(C(C)(C)C)C=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC1=NN=NN1 SRZKBYNNCQFTFV-UHFFFAOYSA-N 0.000 claims description 2
OPHHMFYPCBMHNT-UHFFFAOYSA-N 1-[2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-3-pentylindol-1-yl]ethanone Chemical compound CC(=O)N1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 OPHHMFYPCBMHNT-UHFFFAOYSA-N 0.000 claims description 2
OUFFKANICABSLH-UHFFFAOYSA-N 1-[3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]indol-1-yl]ethanone Chemical compound CC(=O)N1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC1=NN=NN1 OUFFKANICABSLH-UHFFFAOYSA-N 0.000 claims description 2
BPYFWNGIPZCIAT-UHFFFAOYSA-N 1-benzyl-2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-3-pentylindole Chemical compound C=1C=CC=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 BPYFWNGIPZCIAT-UHFFFAOYSA-N 0.000 claims description 2
BDPXZFKVHDEPIQ-UHFFFAOYSA-N 1-benzyl-3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]indole Chemical compound C=1C=CC=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC=1N=NNN=1 BDPXZFKVHDEPIQ-UHFFFAOYSA-N 0.000 claims description 2
BUMHVJNXFPVEMO-UHFFFAOYSA-N 1-methyl-3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]indole Chemical compound CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC1=NN=NN1 BUMHVJNXFPVEMO-UHFFFAOYSA-N 0.000 claims description 2
XVZQHCZCEZTSKR-UHFFFAOYSA-N 2-[1-bromo-6-(1-methyl-3-pentylindol-2-yl)naphthalen-2-yl]oxyacetic acid Chemical compound CN1C2=CC=CC=C2C(CCCCC)=C1C1=CC=C(C(Br)=C(OCC(O)=O)C=C2)C2=C1 XVZQHCZCEZTSKR-UHFFFAOYSA-N 0.000 claims description 2
UGVQLUVEIHRNFD-UHFFFAOYSA-N 2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-1-[(4-tert-butylphenyl)methyl]-3-pentylindole Chemical compound C=1C=C(C(C)(C)C)C=CC=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 UGVQLUVEIHRNFD-UHFFFAOYSA-N 0.000 claims description 2
AAWAZICAXDCTFO-UHFFFAOYSA-N 2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-1-methyl-3-pentylindole Chemical compound CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 AAWAZICAXDCTFO-UHFFFAOYSA-N 0.000 claims description 2
NJGPFBJGXYWQGI-UHFFFAOYSA-N 2-[5-bromo-6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-3-pentyl-1-[[2-(trifluoromethyl)phenyl]methyl]indole Chemical compound C=1C=CC=C(C(F)(F)F)C=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C(Br)=C2OCC1=NN=NN1 NJGPFBJGXYWQGI-UHFFFAOYSA-N 0.000 claims description 2
SJDRBMZDCCSQEB-UHFFFAOYSA-N 3-pentyl-2-[6-(2h-tetrazol-5-ylmethoxy)naphthalen-2-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]indole Chemical compound C=1C=CC=C(C(F)(F)F)C=1CN1C2=CC=CC=C2C(CCCCC)=C1C(C=C1C=C2)=CC=C1C=C2OCC1=NN=NN1 SJDRBMZDCCSQEB-UHFFFAOYSA-N 0.000 claims description 2
229910018828 PO3H2 Inorganic materials 0.000 claims description 2
229910006069 SO3H Inorganic materials 0.000 claims description 2
239000000654 additive Substances 0.000 claims description 2
150000001540 azides Chemical class 0.000 claims description 2
230000006735 deficit Effects 0.000 claims description 2
230000003278 mimic effect Effects 0.000 claims description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 6
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
230000000996 additive effect Effects 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
239000007787 solid Substances 0.000 description 52
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 48
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 43
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238000001819 mass spectrum Methods 0.000 description 32
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102000012335 Plasminogen Activator Inhibitor 1 Human genes 0.000 description 24
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Health & Medical Sciences (AREA)
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Animal Behavior & Ethology (AREA)
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Pharmacology & Pharmacy (AREA)
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NO20035635A 2001-06-20 2003-12-17 Substituerte naftylindol-derivater, fremgangsmate for fremstilling av disse, farmasoytiske preparater inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom. NO326316B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US29965101P	2001-06-20	2001-06-20
PCT/US2002/021113 WO2003000684A1 (en)	2001-06-20	2002-06-18	Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (pai-1)

Publications (2)

Publication Number	Publication Date
NO20035635D0 NO20035635D0 (no)	2003-12-17
NO326316B1 true NO326316B1 (no)	2008-11-10

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Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO20035635A NO326316B1 (no)	2001-06-20	2003-12-17	Substituerte naftylindol-derivater, fremgangsmate for fremstilling av disse, farmasoytiske preparater inneholdende slike forbindelser samt anvendelse av slike forbindelser for fremstilling av medikament for behandling av sykdom.
NO20084390A NO20084390L (no)	2001-06-20	2008-10-20	Substituerte naftylindol-derivater som inhibitorer av plasminogen-aktivatorinhibitor type-1 (PAI-1)

Family Applications After (1)

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NO20084390A NO20084390L (no)	2001-06-20	2008-10-20	Substituerte naftylindol-derivater som inhibitorer av plasminogen-aktivatorinhibitor type-1 (PAI-1)

Country Status (25)

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US (4)	US6800654B2 (es)
EP (1)	EP1397356B1 (es)
JP (1)	JP4520144B2 (es)
KR (1)	KR20040007744A (es)
CN (1)	CN1280288C (es)
AR (1)	AR036101A1 (es)
AT (1)	ATE431346T1 (es)
AU (1)	AU2002316533B2 (es)
BR (1)	BR0210504A (es)
CA (1)	CA2448798C (es)
CO (1)	CO5540286A2 (es)
DE (1)	DE60232328D1 (es)
EA (1)	EA009696B1 (es)
EC (1)	ECSP034904A (es)
ES (1)	ES2325733T3 (es)
HU (1)	HUP0400233A3 (es)
IL (1)	IL159449A0 (es)
MX (1)	MXPA03011522A (es)
NO (2)	NO326316B1 (es)
NZ (1)	NZ530312A (es)
PL (1)	PL367525A1 (es)
TW (1)	TWI224101B (es)
UA (1)	UA78708C2 (es)
WO (1)	WO2003000684A1 (es)
ZA (1)	ZA200400380B (es)

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Publication number	Priority date	Publication date	Assignee	Title
TWI224101B (en) *	2001-06-20	2004-11-21	Wyeth Corp	Substituted naphthyl indole derivatives as inhibitors of plasminogen activator inhibitor type-1 (PAI-1)
US7291639B2 (en) *	2001-06-20	2007-11-06	Wyeth	Aryloxy-acetic acid compounds useful as inhibitors of plasminogen activator inhibitor-1 (PAI-1)
ATE367812T1 (de) *	2001-06-20	2007-08-15	Wyeth Corp	Substituierte indolsäurederivate als inhibitoren von plasminogen-aktivator-inhibitor-1 (pai-1)
CN1726191A (zh) *	2002-12-10	2006-01-25	惠氏公司	用作纤溶酶原激活物抑制剂－1(pai－1)的抑制剂的取代的吲哚氧代－乙酰氨基乙酸衍生物
UA80453C2 (en) *	2002-12-10	2007-09-25		Derivatives of substituted dyhydropyranoindol-3,4-dion as inhibitors of plasminogen activator inhibitor-1 (pai-1)
ES2268480T3 (es) *	2002-12-10	2007-03-16	Wyeth	Derivados del acido 3-alquilo- y 3-arilalquilo-1h-indol-1-il-acetico sustituidos como inhibidores del inhibidor del activador del plasminogeno-1 (pai-1).
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2002
- 2002-06-10 TW TW091112530A patent/TWI224101B/zh not_active IP Right Cessation
- 2002-06-13 US US10/171,041 patent/US6800654B2/en not_active Expired - Fee Related
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2003
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Also Published As

Publication number	Publication date
DE60232328D1 (de)	2009-06-25
EA200400054A1 (ru)	2004-04-29
NO20035635D0 (no)	2003-12-17
WO2003000684A1 (en)	2003-01-03
CN1280288C (zh)	2006-10-18
ES2325733T3 (es)	2009-09-15
US20080182883A1 (en)	2008-07-31
EA009696B1 (ru)	2008-02-28
PL367525A1 (en)	2005-02-21
ECSP034904A (es)	2004-01-28
US20030032626A1 (en)	2003-02-13
AU2002316533B2 (en)	2007-10-18
US6939886B2 (en)	2005-09-06
EP1397356A1 (en)	2004-03-17
CN1549814A (zh)	2004-11-24
HUP0400233A2 (hu)	2004-08-30
HUP0400233A3 (en)	2008-10-28
JP4520144B2 (ja)	2010-08-04
EP1397356B1 (en)	2009-05-13
NZ530312A (en)	2005-05-27
KR20040007744A (ko)	2004-01-24
IL159449A0 (en)	2004-06-01
JP2004534825A (ja)	2004-11-18
US20040266733A1 (en)	2004-12-30
UA78708C2 (en)	2007-04-25
BR0210504A (pt)	2004-05-18
CO5540286A2 (es)	2005-07-29
TWI224101B (en)	2004-11-21
ZA200400380B (en)	2006-06-28
US20060014725A1 (en)	2006-01-19
ATE431346T1 (de)	2009-05-15
US7629377B2 (en)	2009-12-08
CA2448798C (en)	2010-07-20
NO20084390L (no)	2003-12-17
US6800654B2 (en)	2004-10-05
CA2448798A1 (en)	2003-01-03
MXPA03011522A (es)	2004-03-19
AR036101A1 (es)	2004-08-11
US7351730B2 (en)	2008-04-01

Publication	Publication Date	Title
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