OA12928A - Novel imidazole compounds as transforming growth factor (TGF) inhibitors. - Google Patents

Novel imidazole compounds as transforming growth factor (TGF) inhibitors. Download PDF

Info

Publication number: OA12928A
Authority: OA; OAPI
Prior art keywords: alkyl; cio; phenyl; cycloalkyl; heteroaryl
Prior art date: 2002-09-18

Application number

OA1200500077A

Other languages

English (en)

Inventor

Laura Cook Blumberg

Michael John Munchhof

Original Assignee

Pfizer Prod 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.)

2002-09-18

Filing date

2003-09-08

Publication date

2006-10-13

2003-09-08 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2006-10-13 Publication of OA12928A publication Critical patent/OA12928A/en

Links

102000009618 Transforming Growth Factors Human genes 0.000 title abstract description 17
108010009583 Transforming Growth Factors Proteins 0.000 title abstract description 17
239000003112 inhibitor Substances 0.000 title abstract description 11
150000002460 imidazoles Chemical class 0.000 title abstract description 3
150000001875 compounds Chemical class 0.000 claims abstract description 171
-1 derivatives thereof Chemical class 0.000 claims abstract description 75
201000010099 disease Diseases 0.000 claims abstract description 19
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
206010028980 Neoplasm Diseases 0.000 claims abstract description 6
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
201000011510 cancer Diseases 0.000 claims abstract description 4
125000000217 alkyl group Chemical group 0.000 claims description 148
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 46
125000003545 alkoxy group Chemical group 0.000 claims description 44
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 30
125000000753 cycloalkyl group Chemical group 0.000 claims description 29
125000003118 aryl group Chemical group 0.000 claims description 25
125000004122 cyclic group Chemical group 0.000 claims description 25
125000001072 heteroaryl group Chemical group 0.000 claims description 24
125000000623 heterocyclic group Chemical group 0.000 claims description 23
239000000651 prodrug Substances 0.000 claims description 20
229940002612 prodrug Drugs 0.000 claims description 20
229910052739 hydrogen Inorganic materials 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 17
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
125000005842 heteroatom Chemical group 0.000 claims description 15
125000003282 alkyl amino group Chemical group 0.000 claims description 13
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 11
125000000304 alkynyl group Chemical group 0.000 claims description 10
229910052717 sulfur Inorganic materials 0.000 claims description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
125000003342 alkenyl group Chemical group 0.000 claims description 9
125000001424 substituent group Chemical group 0.000 claims description 9
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 8
229920006395 saturated elastomer Polymers 0.000 claims description 8
241001465754 Metazoa Species 0.000 claims description 7
150000002148 esters Chemical class 0.000 claims description 7
150000002431 hydrogen Chemical class 0.000 claims description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
125000001624 naphthyl group Chemical group 0.000 claims description 7
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 7
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 6
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 6
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
125000003368 amide group Chemical group 0.000 claims description 5
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
125000004103 aminoalkyl group Chemical group 0.000 claims description 4
125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
125000003367 polycyclic group Chemical group 0.000 claims description 4
125000004076 pyridyl group Chemical group 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000005129 aryl carbonyl group Chemical group 0.000 claims description 3
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 3
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 3
206010018364 Glomerulonephritis Diseases 0.000 claims description 2
206010019668 Hepatic fibrosis Diseases 0.000 claims description 2
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
206010020718 hyperplasia Diseases 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
208000005069 pulmonary fibrosis Diseases 0.000 claims description 2
208000037803 restenosis Diseases 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims 12
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 1
125000006529 (C3-C6) alkyl group Chemical group 0.000 claims 1
208000007342 Diabetic Nephropathies Diseases 0.000 claims 1
206010039710 Scleroderma Diseases 0.000 claims 1
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 1
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239000000543 intermediate Substances 0.000 abstract description 9
230000019491 signal transduction Effects 0.000 abstract description 7
230000003389 potentiating effect Effects 0.000 abstract description 3
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238000006243 chemical reaction Methods 0.000 description 48
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238000000034 method Methods 0.000 description 37
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239000002904 solvent Substances 0.000 description 23
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239000002585 base Substances 0.000 description 21
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125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
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108090001012 Transforming Growth Factor beta Proteins 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
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ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 7
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
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235000011152 sodium sulphate Nutrition 0.000 description 5
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MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 description 1
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230000003595 spectral effect Effects 0.000 description 1
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IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
OSBSFAARYOCBHB-UHFFFAOYSA-N tetrapropylammonium Chemical compound CCC[N+](CCC)(CCC)CCC OSBSFAARYOCBHB-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
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MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
230000005751 tumor progression Effects 0.000 description 1
229960002004 valdecoxib Drugs 0.000 description 1
LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
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OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A—HUMAN NECESSITIES
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- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- 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
- C07D405/14—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 three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

Chemical & Material Sciences (AREA)
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General Chemical & Material Sciences (AREA)
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Gastroenterology & Hepatology (AREA)
Urology & Nephrology (AREA)
Dermatology (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
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OA1200500077A 2002-09-18 2003-09-08 Novel imidazole compounds as transforming growth factor (TGF) inhibitors. OA12928A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US41189402P	2002-09-18	2002-09-18
US48452203P	2003-07-02	2003-07-02

Publications (1)

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OA12928A true OA12928A (en)	2006-10-13

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OA1200500077A OA12928A (en)	2002-09-18	2003-09-08	Novel imidazole compounds as transforming growth factor (TGF) inhibitors.

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US (2)	US7153872B2 (es)
EP (1)	EP1542990B1 (es)
JP (1)	JP4547271B2 (es)
KR (1)	KR20050057392A (es)
CN (1)	CN1681805A (es)
AP (1)	AP2005003264A0 (es)
AR (1)	AR041274A1 (es)
AT (1)	ATE433968T1 (es)
AU (1)	AU2003263404A1 (es)
BR (1)	BR0314372A (es)
CA (1)	CA2498047C (es)
CO (1)	CO5550453A2 (es)
DE (1)	DE60328028D1 (es)
EA (1)	EA200500378A1 (es)
EC (1)	ECSP055680A (es)
ES (1)	ES2325687T3 (es)
HR (1)	HRP20050252A2 (es)
IS (1)	IS7712A (es)
MA (1)	MA27441A1 (es)
MX (1)	MXPA05002981A (es)
NO (1)	NO20051008L (es)
OA (1)	OA12928A (es)
PA (1)	PA8583301A1 (es)
PE (1)	PE20050072A1 (es)
PL (1)	PL375980A1 (es)
TW (1)	TW200404793A (es)
UY (1)	UY27982A1 (es)
WO (1)	WO2004026859A1 (es)

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- 2003-09-08 OA OA1200500077A patent/OA12928A/en unknown
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- 2003-09-08 DE DE60328028T patent/DE60328028D1/de not_active Expired - Lifetime
- 2003-09-08 CN CNA038221608A patent/CN1681805A/zh active Pending
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- 2003-09-08 HR HR20050252A patent/HRP20050252A2/hr not_active Application Discontinuation
- 2003-09-08 WO PCT/IB2003/003833 patent/WO2004026859A1/en not_active Ceased
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- 2005-03-18 MA MA28155A patent/MA27441A1/fr unknown
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Also Published As

Publication number	Publication date
DE60328028D1 (de)	2009-07-30
US20040106608A1 (en)	2004-06-03
ECSP055680A (es)	2005-05-30
UY27982A1 (es)	2004-04-30
US7153872B2 (en)	2006-12-26
US20070088037A1 (en)	2007-04-19
IS7712A (is)	2005-02-24
JP4547271B2 (ja)	2010-09-22
PL375980A1 (en)	2005-12-12
ATE433968T1 (de)	2009-07-15
JP2006502237A (ja)	2006-01-19
EA200500378A1 (ru)	2005-08-25
BR0314372A (pt)	2005-07-19
TW200404793A (en)	2004-04-01
EP1542990A1 (en)	2005-06-22
CA2498047C (en)	2009-05-19
CA2498047A1 (en)	2004-04-01
MA27441A1 (fr)	2005-07-01
US7635702B2 (en)	2009-12-22
NO20051008L (no)	2005-06-07
AP2005003264A0 (en)	2005-03-31
AR041274A1 (es)	2005-05-11
AU2003263404A1 (en)	2004-04-08
CO5550453A2 (es)	2005-08-31
HRP20050252A2 (en)	2005-10-31
EP1542990B1 (en)	2009-06-17
CN1681805A (zh)	2005-10-12
WO2004026859A1 (en)	2004-04-01
KR20050057392A (ko)	2005-06-16
MXPA05002981A (es)	2005-06-22
ES2325687T3 (es)	2009-09-14
PA8583301A1 (es)	2004-09-16
PE20050072A1 (es)	2005-03-01

Publication	Publication Date	Title
OA12928A (en)	2006-10-13	Novel imidazole compounds as transforming growth factor (TGF) inhibitors.
CA2496295C (en)	2010-11-23	Novels pyrazole compounds as transforming growth factor (tgf) inhibitors
EP1606267B1 (en)	2008-07-30	Pyrazine compounds as transforming growth factor (tgf) inhibitors
US7273936B2 (en)	2007-09-25	Oxazole and thiazole compounds as transforming growth factor (TGF) inhibitors
US20040110798A1 (en)	2004-06-10	Novel triazole compounds as transforming growth factors (TGF) inhibitors
WO2004026865A1 (en)	2004-04-01	Novel isothiazole and isoxazole compounds as transforming growth factor (tgf) inhibitors