OA11084A - 2-Amino--6-(2-substituted-4-phenoxy)-substituted- pyridines - Google Patents

2-Amino--6-(2-substituted-4-phenoxy)-substituted- pyridines Download PDF

Info

Publication number: OA11084A
Authority: OA; OAPI
Prior art keywords: alkyl; formula; nmr; disease; nitrogen
Prior art date: 1997-02-10

Application number

OA9900173A

Other languages

English (en)

Inventor

John Adams Lowe Iii

Jolanta Nowakowski

Robert Alfred Volkmann

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.)

1997-02-10

Filing date

1999-08-06

Publication date

2002-03-15

1999-08-06 Application filed by Pfizer Prod Inc filed Critical Pfizer Prod Inc

2002-03-15 Publication of OA11084A publication Critical patent/OA11084A/en

Links

150000001875 compounds Chemical class 0.000 claims abstract description 167
102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 26
108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 26
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 56
125000000217 alkyl group Chemical group 0.000 claims description 46
-1 nitro, hydroxy, cyano, amino Chemical group 0.000 claims description 37
238000000034 method Methods 0.000 claims description 32
229910052757 nitrogen Inorganic materials 0.000 claims description 31
125000001424 substituent group Chemical group 0.000 claims description 23
239000001257 hydrogen Substances 0.000 claims description 21
229910052739 hydrogen Inorganic materials 0.000 claims description 21
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 20
241000124008 Mammalia Species 0.000 claims description 19
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 19
206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 16
208000002193 Pain Diseases 0.000 claims description 16
208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 16
230000001154 acute effect Effects 0.000 claims description 16
208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 16
201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 16
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
125000005843 halogen group Chemical group 0.000 claims description 11
230000002401 inhibitory effect Effects 0.000 claims description 11
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 11
206010040070 Septic Shock Diseases 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 10
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
206010028980 Neoplasm Diseases 0.000 claims description 9
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 9
201000011510 cancer Diseases 0.000 claims description 9
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208000019695 Migraine disease Diseases 0.000 claims description 8
208000028017 Psychotic disease Diseases 0.000 claims description 8
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208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 8
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201000006704 Ulcerative Colitis Diseases 0.000 claims description 8
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125000004122 cyclic group Chemical group 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
230000035939 shock Effects 0.000 claims description 7
208000030507 AIDS Diseases 0.000 claims description 6
208000024827 Alzheimer disease Diseases 0.000 claims description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
125000003282 alkyl amino group Chemical group 0.000 claims description 6
125000003710 aryl alkyl group Chemical group 0.000 claims description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 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
210000002569 neuron Anatomy 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
239000001301 oxygen Substances 0.000 claims description 6
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 6
230000001988 toxicity Effects 0.000 claims description 6
231100000419 toxicity Toxicity 0.000 claims description 6
125000004429 atom Chemical group 0.000 claims description 5
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125000001153 fluoro group Chemical group F* 0.000 claims description 5
150000002431 hydrogen Chemical class 0.000 claims description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
208000007342 Diabetic Nephropathies Diseases 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
125000003118 aryl group Chemical group 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
208000033679 diabetic kidney disease Diseases 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000001624 naphthyl group Chemical group 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
125000006678 phenoxycarbonyl group Chemical group 0.000 claims description 3
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
JAKNYTQAGPEFJB-UHFFFAOYSA-N piperidin-2-amine Chemical group NC1CCCCN1 JAKNYTQAGPEFJB-UHFFFAOYSA-N 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 claims description 2
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
125000004432 carbon atom Chemical group C* 0.000 claims 2
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 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
229940125810 compound 20 Drugs 0.000 claims 1
108010041382 compound 20 Proteins 0.000 claims 1
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 9
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238000005160 1H NMR spectroscopy Methods 0.000 description 111
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238000006243 chemical reaction Methods 0.000 description 48
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 47
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235000019439 ethyl acetate Nutrition 0.000 description 44
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Classifications

- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
- A—HUMAN NECESSITIES
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- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P27/06—Antiglaucoma agents or miotics
- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/08—Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock
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- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
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Heart & Thoracic Surgery (AREA)
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Diabetes (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyridine Compounds (AREA)
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Hydrogenated Pyridines (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

OA9900173A 1997-02-10 1999-08-06 2-Amino--6-(2-substituted-4-phenoxy)-substituted- pyridines OA11084A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US3753397P	1997-02-10	1997-02-10

Publications (1)

Publication Number	Publication Date
OA11084A true OA11084A (en)	2002-03-15

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ID=21894849

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA9900173A OA11084A (en)	1997-02-10	1999-08-06	2-Amino--6-(2-substituted-4-phenoxy)-substituted- pyridines

Country Status (44)

Country	Link
US (2)	US20010007873A1 (fr)
EP (1)	EP0958282B1 (fr)
JP (1)	JP3505189B2 (fr)
KR (1)	KR100460399B1 (fr)
CN (3)	CN1246848A (fr)
AP (1)	AP833A (fr)
AR (1)	AR011117A1 (fr)
AT (1)	ATE271544T1 (fr)
AU (1)	AU744313B2 (fr)
BG (1)	BG103633A (fr)
BR (1)	BR9811093A (fr)
CA (1)	CA2277990C (fr)
CO (1)	CO4920225A1 (fr)
CZ (1)	CZ292135B6 (fr)
DE (1)	DE69825147T2 (fr)
DK (1)	DK0958282T3 (fr)
DZ (1)	DZ2414A1 (fr)
EA (1)	EA003834B1 (fr)
ES (1)	ES2224354T3 (fr)
GT (1)	GT199800032A (fr)
HN (1)	HN1998000030A (fr)
HR (1)	HRP980069A2 (fr)
HU (1)	HUP0000762A3 (fr)
IL (1)	IL130898A0 (fr)
IS (1)	IS5118A (fr)
MA (1)	MA27676A1 (fr)
MY (1)	MY120976A (fr)
NO (1)	NO314803B1 (fr)
NZ (2)	NZ518345A (fr)
OA (1)	OA11084A (fr)
PA (1)	PA8446301A1 (fr)
PE (1)	PE58599A1 (fr)
PL (1)	PL335161A1 (fr)
PT (1)	PT958282E (fr)
SI (1)	SI0958282T1 (fr)
SK (1)	SK101199A3 (fr)
TN (1)	TNSN98024A1 (fr)
TR (1)	TR199901917T2 (fr)
TW (1)	TW458969B (fr)
UA (1)	UA64740C2 (fr)
UY (1)	UY24881A1 (fr)
WO (1)	WO1998034919A1 (fr)
YU (1)	YU35699A (fr)
ZA (1)	ZA981017B (fr)

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20010049379A1 (en)	1997-08-27	2001-12-06	Lowe John Adams	2-aminopyridines containing fused ring substituents
HRP20000825A2 (en) *	1998-06-03	2001-12-31	Pfizer Prod Inc	2-aminopyridines containing fused ring substituents as nitric oxide synthase inhibitors
HRP20010099A2 (en) *	1998-08-11	2002-02-28	Pfizer Prod Inc	New pharmaceutical uses for nos inhibitors
SE9803710L (sv)	1998-09-25	2000-03-26	A & Science Invest Ab	Användning av vissa substanser för behandling av nervrotsskador
US7115557B2 (en)	1998-09-25	2006-10-03	Sciaticon Ab	Use of certain drugs for treating nerve root injury
CN1341099A (zh)	1999-02-25	2002-03-20	辉瑞产品公司	含有稠合环取代基的2－氨基吡啶
FR2812635B1 (fr) *	2000-08-01	2002-10-11	Aventis Pharma Sa	Nouveaux composes heterocycliques, preparation et utilisation comme medicaments notamment comme anti- bacteriens
GB0019006D0 (en) *	2000-08-04	2000-09-20	Astrazeneca Ab	Novel compounds
US20030232739A1 (en) *	2001-08-15	2003-12-18	Pfizer Inc.	Pharmaceutical combinations comprising a NOS inhibitor and an NMDA receptor antagonist
US20030045449A1 (en) *	2001-08-15	2003-03-06	Pfizer, Inc.	Pharmaceutical combinations for the treatment of neurodegenerative diseases
DOP2002000467A (es) *	2001-10-10	2003-04-15	Pfizer Prod Inc	2-amino-6 (fenilo sustituido en las posiciones 2,4,5)-piridinas
US6803470B2 (en)	2001-10-10	2004-10-12	Pfizer Inc	2-amino-6-(2,4,5-substituted-phenyl)-pyridines
US7045652B2 (en)	2002-07-03	2006-05-16	Pfizer Inc	Processes for preparing substituted aryl boronic acids
US20040092741A1 (en) *	2002-11-08	2004-05-13	Pfizer Inc	Substituted pyridines via boronic acid coupling
WO2005007627A1 (fr) *	2003-07-18	2005-01-27	Nihon Nohyaku Co., Ltd.	Derive de phenylpyridine, produit intermediaire correspondant, et herbicide contenant ledit derive de phenylpyridine en tant qu'ingredient actif
US20080070952A1 (en) *	2005-02-21	2008-03-20	Proximagen Ltd.,	Inhibition or Treatment of Dyskinesia
GB0607196D0 (en) *	2006-04-11	2006-05-17	Prosidion Ltd	G-protein coupled receptor agonists
AR064572A1 (es) *	2006-12-28	2009-04-08	Basf Ag	Derivados de piridina 2-sustituidas, una composicion farmaceutica que las comprende y su uso en la preparacion de un medicamento para el tratamiento del cancer.
UA105182C2 (ru)	2008-07-03	2014-04-25	Ньюрексон, Інк.	Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность
KR101735787B1 (ko)	2013-02-28	2017-05-16	주식회사 티움바이오	삼환식 화합물 및 이의 용도
EP3066072B1 (fr) *	2013-11-07	2021-11-03	The University of Kansas	Inhibiteurs de hsp90 dérivés de biphénylamide
AR101510A1 (es) *	2014-08-13	2016-12-21	Meiji Seika Pharma Co Ltd	Agentes anti-trichophyton cristalinos y proceso de preparación de los mismos
CN106265640B (zh) *	2016-08-11	2019-05-14	吉林大学	Appa在制备治疗糖尿病肾病药物中的应用
CN108069831B (zh) *	2018-01-25	2020-11-24	上海恩氟佳科技有限公司	一种合成2,3-二甲基-4-氟苯酚的方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPH08504798A (ja) *	1992-12-18	1996-05-21	ザウエルカムファウンデーションリミテッド	酵素阻害薬としての，ピリミジン，ピリジン，プテリジノンおよびインダゾール誘導体
KR100342275B1 (ko) *	1993-10-21	2002-12-05	지.디. 썰 엘엘씨	산화질소신타제저해제로서유용한아미디노유도체
AU4515696A (en) *	1994-12-12	1996-07-03	Merck & Co., Inc.	Substituted 2-aminopyridines as inhibitors of nitric oxide synthase
UA49006C2 (uk) *	1996-03-29	2002-09-16	Файзер Інк.	Похідні 6-фенілпіридил-2-аміну, фармацевтична композиція, спосіб інгібування синтази оксиду нітрогену у ссавців та спосіб лікування

1998
- 1998-01-29 WO PCT/IB1998/000112 patent/WO1998034919A1/fr not_active Ceased
- 1998-01-29 TR TR1999/01917T patent/TR199901917T2/xx unknown
- 1998-01-29 UA UA99084543A patent/UA64740C2/uk unknown
- 1998-01-29 PT PT98900635T patent/PT958282E/pt unknown
- 1998-01-29 CN CN98802392A patent/CN1246848A/zh active Pending
- 1998-01-29 YU YU35699A patent/YU35699A/sh unknown
- 1998-01-29 SK SK1011-99A patent/SK101199A3/sk unknown
- 1998-01-29 AU AU55727/98A patent/AU744313B2/en not_active Ceased
- 1998-01-29 BR BR9811093-4A patent/BR9811093A/pt not_active Application Discontinuation
- 1998-01-29 KR KR10-1999-7007065A patent/KR100460399B1/ko not_active Expired - Fee Related
- 1998-01-29 DE DE69825147T patent/DE69825147T2/de not_active Expired - Fee Related
- 1998-01-29 CN CNA2004100073282A patent/CN1523015A/zh active Pending
- 1998-01-29 EP EP98900635A patent/EP0958282B1/fr not_active Expired - Lifetime
- 1998-01-29 AT AT98900635T patent/ATE271544T1/de not_active IP Right Cessation
- 1998-01-29 ES ES98900635T patent/ES2224354T3/es not_active Expired - Lifetime
- 1998-01-29 EA EA199900632A patent/EA003834B1/ru not_active IP Right Cessation
- 1998-01-29 SI SI9830699T patent/SI0958282T1/xx unknown
- 1998-01-29 NZ NZ518345A patent/NZ518345A/en unknown
- 1998-01-29 IL IL13089898A patent/IL130898A0/xx unknown
- 1998-01-29 CA CA002277990A patent/CA2277990C/fr not_active Expired - Fee Related
- 1998-01-29 JP JP53404898A patent/JP3505189B2/ja not_active Expired - Fee Related
- 1998-01-29 PL PL98335161A patent/PL335161A1/xx unknown
- 1998-01-29 HU HU0000762A patent/HUP0000762A3/hu unknown
- 1998-01-29 CZ CZ19992769A patent/CZ292135B6/cs not_active IP Right Cessation
- 1998-01-29 CN CNA031086047A patent/CN1515554A/zh active Pending
- 1998-01-29 DK DK98900635T patent/DK0958282T3/da active
- 1998-01-29 NZ NZ336623A patent/NZ336623A/xx unknown
- 1998-02-03 TW TW087101311A patent/TW458969B/zh not_active IP Right Cessation
- 1998-02-05 PE PE1998000082A patent/PE58599A1/es not_active Application Discontinuation
- 1998-02-05 AP APAP/P/1998/001178A patent/AP833A/en active
- 1998-02-06 UY UY24881A patent/UY24881A1/es not_active Application Discontinuation
- 1998-02-06 MY MYPI98000488A patent/MY120976A/en unknown
- 1998-02-09 HN HN1998000030A patent/HN1998000030A/es unknown
- 1998-02-09 TN TNTNSN98024A patent/TNSN98024A1/fr unknown
- 1998-02-09 ZA ZA9801017A patent/ZA981017B/xx unknown
- 1998-02-09 MA MA24958A patent/MA27676A1/fr unknown
- 1998-02-09 DZ DZ980024A patent/DZ2414A1/fr active
- 1998-02-09 AR ARP980100551A patent/AR011117A1/es not_active Application Discontinuation
- 1998-02-10 HR HR60/037,533A patent/HRP980069A2/hr not_active Application Discontinuation
- 1998-02-10 PA PA19988446301A patent/PA8446301A1/es unknown
- 1998-02-10 CO CO98006875A patent/CO4920225A1/es unknown
- 1998-02-11 GT GT199800032A patent/GT199800032A/es unknown
- 1998-07-31 US US09/127,158 patent/US20010007873A1/en not_active Abandoned
1999
- 1999-07-16 IS IS5118A patent/IS5118A/is unknown
- 1999-08-03 BG BG103633A patent/BG103633A/bg unknown
- 1999-08-06 OA OA9900173A patent/OA11084A/en unknown
- 1999-08-09 NO NO19993823A patent/NO314803B1/no unknown
2003
- 2003-02-20 US US10/371,357 patent/US20030162765A1/en not_active Abandoned

Also Published As

Publication number	Publication date
DE69825147D1 (de)	2004-08-26
YU35699A (sh)	2002-06-19
EP0958282A1 (fr)	1999-11-24
HN1998000030A (es)	1998-10-22
PE58599A1 (es)	1999-06-12
IL130898A0 (en)	2001-01-28
KR100460399B1 (ko)	2004-12-08
BG103633A (bg)	2000-11-30
UY24881A1 (es)	2000-12-29
AU744313B2 (en)	2002-02-21
AR011117A1 (es)	2000-08-02
TNSN98024A1 (fr)	2005-03-15
CZ276999A3 (cs)	2000-05-17
PA8446301A1 (es)	2000-05-24
JP3505189B2 (ja)	2004-03-08
PT958282E (pt)	2004-11-30
IS5118A (is)	1999-07-29
CA2277990A1 (fr)	1998-08-13
NO993823L (no)	1999-08-09
CN1246848A (zh)	2000-03-08
CO4920225A1 (es)	2000-05-29
HRP980069A2 (en)	1998-12-31
US20010007873A1 (en)	2001-07-12
WO1998034919A1 (fr)	1998-08-13
ZA981017B (en)	1999-08-10
GT199800032A (es)	1998-02-11
CA2277990C (fr)	2006-08-01
NO993823D0 (no)	1999-08-09
CN1515554A (zh)	2004-07-28
MA27676A1 (fr)	2006-01-02
SK101199A3 (en)	2000-10-09
NO314803B1 (no)	2003-05-26
TR199901917T2 (xx)	1999-12-21
DZ2414A1 (fr)	2003-01-04
CN1523015A (zh)	2004-08-25
AP833A (en)	2000-05-10
UA64740C2 (uk)	2004-03-15
DK0958282T3 (da)	2004-11-29
EP0958282B1 (fr)	2004-07-21
CZ292135B6 (cs)	2003-08-13
EA199900632A1 (ru)	2000-02-28
TW458969B (en)	2001-10-11
JP2000509408A (ja)	2000-07-25
KR20000070803A (ko)	2000-11-25
AU5572798A (en)	1998-08-26
MY120976A (en)	2005-12-30
US20030162765A1 (en)	2003-08-28
EA003834B1 (ru)	2003-10-30
ES2224354T3 (es)	2005-03-01
HUP0000762A3 (en)	2000-10-30
SI0958282T1 (en)	2005-02-28
PL335161A1 (en)	2000-04-10
BR9811093A (pt)	2000-07-18
DE69825147T2 (de)	2005-08-04
HUP0000762A2 (hu)	2000-09-28
NZ336623A (en)	2000-11-24
NZ518345A (en)	2005-02-25
ATE271544T1 (de)	2004-08-15

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