公开(公告)号：EP1856098B1

公开(公告)日：2012-08-01

申请号：EP06735090.0

申请日：2006-02-14

申请人： Schering Corporation ,  Pharmacopeia, LLC

发明人： ROSENBLUM, Stuart, B. ,  KIM, Seong, Heon ,  ZENG, Qingbei ,  WONG, Michael K.C. ,  ANILKUMAR, Gopinadhan, N. ,  JIANG, Yueheng ,  YU, Wensheng ,  KOZLOWSKI, Joseph, A. ,  SHIH, Neng-Yang ,  SHANKAR, Bandarpalle, B. ,  MCGUINNESS, Brian, F. ,  DONG, Guizhen ,  ZAWACKI, Lisa, Guise ,  HOBBS, Douglas, W. ,  BALDWIN, John, J. ,  SHAO, Yuefei

IPC分类号： C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/14 ,  A61K31/445 ,  A61K31/495

CPC分类号： C07D405/14 ,  C07D401/12 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14

摘要： The present application discloses a compound, or enantiomers, stereoisomers, rotamers, tautomers, racemates or prodrug of said compound, or pharmaceutically acceptable salts, solvates or esters of said compound, or of said prodrug, said compound having the general structure shown in Formula (1): Chemical formula should be inserted here as it appears on the abstract in paper form. and the pharmaceutically acceptable salts, solvates and esters thereof. Also disclosed is a method of treating chemokine mediated diseases, such as, palliative therapy, curative therapy, prophylactic therapy of certain diseases and conditions such as inflammatory diseases (non limiting example(s) include, psoriasis), autoimmune diseases (non limiting example(s) include, rheumatoid arthritis, multiple sclerosis), graft rejection (non limiting example(s) include, allograft rejection, xenograft rejection), infectious diseases (e.g., tuberculoid leprosy), fixed drug eruptions, cutaneous delayed-type hypersensitivity responses, ophthalmic inflammation, type I diabetes, viral meningitis and tumors using a compound of Formula (1).

摘要翻译： 本申请公开了所述化合物的一种或多种对映异构体，立体异构体，旋转异构体，互变异构体，外消旋体或前药，或所述化合物或所述前药的药学上可接受的盐，溶剂合物或酯，所述化合物具有式 1）：化学式应插入此处，因为它以摘要形式出现在纸上。 及其药学上可接受的盐，溶剂化物和酯。 还公开了治疗趋化因子介导的疾病的方法，例如姑息性治疗，治愈性治疗，某些疾病和病症的预防性治疗，例如炎性疾病（非限制性实例包括牛皮癣），自身免疫性疾病（非限制性实例（ 包括类风湿性关节炎，多发性硬化症），移植排斥（非限制性实例包括同种异体移植排斥，异种移植排斥），感染性疾病（例如结核性麻风），固定药疹，皮肤迟发型超敏反应，眼科 炎症，I型糖尿病，病毒性脑膜炎和使用式（1）化合物的肿瘤。

公开(公告)号：EP1697354B1

公开(公告)日：2013-08-07

申请号：EP04814856.3

申请日：2004-12-20

申请人： Merck Sharp & Dohme Corp. ,  Pharmacopeia, LLC

发明人： TAVERAS, Arthur, G. ,  ZHENG, Junying ,  BIJU, Purakkattle, J. ,  YU, Younong ,  CHAO, Jianhua ,  FINE, Jay ,  LUNDELL, Daniel ,  PRIESTLEY, Tony ,  REGGIANI, Angelo ,  MERRITT, J., Robert ,  BALDWIN, John, J. ,  LAI, Gaifa ,  WU, Minglang

IPC分类号： C07D417/12 ,  C07D275/02 ,  C07D417/14 ,  A61K31/427 ,  A61P35/00 ,  A61P29/00

CPC分类号： C07D275/03 ,  C07D417/12 ,  C07D417/14

公开(公告)号：EP1694659B1

公开(公告)日：2008-08-27

申请号：EP04814266.5

申请日：2004-12-16

申请人： Schering Corporation ,  Pharmacopeia Drug Discovery, Inc.

发明人： BIJU, Purakkattle, J. ,  TAVERAS, Arthur, G. ,  YU, Younong ,  ZHENG, Junying ,  CHAO, Jianhua ,  AKI, Cynthia, J. ,  FINE, Jay ,  LUNDELL, Daniel ,  PRIESTLEY, Tony ,  REGGIANI, Angelo ,  MERRITT, J., Robert ,  BALDWIN, John, J.

IPC分类号： C07D285/10 ,  C07D417/12 ,  C07D417/14 ,  A61K31/433 ,  A61K31/4436

CPC分类号： C07D285/10 ,  C07D285/06 ,  C07D417/12 ,  C07D417/14

摘要： Disclosed are novel compounds of Formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and ischemia reperfusion injury, pain (e.g., acute pain, acute and chronic inflammatory pain, and neuropathic pain) using a compound of Formula (IA).

摘要翻译： 公开了式（IA）的新化合物及其药学上可接受的盐和溶剂化物。 包含取代基A的基团的实例包括杂芳基，芳基，杂环烷基，环烷基，芳基，炔基，烯基，氨基烷基，烷基或氨基。 包含取代基B的基团的例子包括芳基和杂芳基。 还公开了治疗趋化因子介导的疾病例如癌症，血管生成，血管生成性眼病，肺部疾病，多发性硬化症，类风湿性关节炎，骨关节炎，中风和局部缺血再灌注损伤，疼痛（例如急性疼痛，急性和慢性 炎症性疼痛和神经性疼痛）使用式（IA）的化合物。

公开(公告)号：EP0989983B1

公开(公告)日：2004-08-11

申请号：EP98928886.5

申请日：1998-06-15

申请人： SCHERING CORPORATION ,  PHARMACOPEIA, INC.

发明人： COOPER, Alan, B. ,  DOLL, Ronald, J. ,  GIRIJAVALLABHAN, Viyyoor, M. ,  GANGULY, Ashit ,  READER, John, C. ,  BALDWIN, John, J. ,  HUANG, Chia-yu

IPC分类号： C07D401/14 ,  A61K31/55 ,  C07D401/04 ,  A61K31/495 ,  A61K31/44

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D405/14

公开(公告)号：EP0820452B1

公开(公告)日：2003-06-04

申请号：EP96911440.4

申请日：1996-04-03

申请人： SCHERING CORPORATION ,  PHARMACOPEIA, INC.

发明人： DOLL, Ronald, J. ,  MALLAMS, Alan, K. ,  AFONSO, Adriano ,  RANE, Dinanath, F. ,  NJOROGE, F., George ,  ROSSMAN, Randall, A. ,  BALDWIN, John, J. ,  LI, Ge ,  READER, John, C.

IPC分类号： C07D401/06 ,  A61K31/495 ,  C07D401/12 ,  C07D295/12 ,  C07D241/04 ,  C07D401/14 ,  C07D405/12 ,  A61K31/44 ,  C07D409/06 ,  C07D417/06

CPC分类号： C07D213/89 ,  C07D211/34 ,  C07D211/38 ,  C07D211/50 ,  C07D213/56 ,  C07D241/04 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  Y02P20/582

摘要： Novel carbonyl piperazinyl and piperidinyl compounds of formula (1.0) or (1.1) and pharmaceutical compositions are disclosed. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel carbonyl piperazinyl or piperidinyl compound to a biological system. In particular, the method inhibits the abnormal growth cells in a mammal such as the human being. A compound of formula (1.0) and (1.1) or a pharmaceutically acceptable salt or solvate thereof, wherein Z is a group which is (i), (ii) or (iii), wherein X1 is CH or N; X2 can be the same or different and can be CH, N, or N-O; b is 0, 1, 2, 3, 4; n and nn independently represent 0, 1, 2, 3, 4 or when X2 is CH, n and nn can be 5; R20 and R21, R1, R2 and R3 are as given in the description.

公开(公告)号：EP0931078A1

公开(公告)日：1999-07-28

申请号：EP97941477.0

申请日：1997-09-11

申请人： SCHERING CORPORATION

发明人： COOLER, Alan, B. ,  MALLANS, Alan, K. ,  GIRIJAVALLABHAN, Viyyoor, M. ,  DOLL, Ronald, J. ,  TAVERAS, Arthur, G. ,  NJOROGE,, F., George ,  BALDWIN, John, J. ,  READER, John, C.

IPC分类号： A61K31 ,  A61P35 ,  C07D401 ,  C07D405 ,  C07F9

CPC分类号： C07D401/14 ,  C07D401/04 ,  C07F9/591 ,  C07F9/65583

摘要： Novel tricyclic compounds of formula (1.0) or a pharmaceutically acceptable salt or solvate thereof, wherein: one of a, b, c, and d represents N or NR9, wherein R9 is O-, -CH¿3? or -(CH2)nCO2H wherein n is 1 to 3, and the remaining a, b, c and d groups represent CR?1 or CR2¿; or each of a, b, c and d is independently selected from CR?1 or CR2¿; each R1 and each R2 is independently selected from H, halo, -CR¿3?, -OR?10, -COR10, -SR10¿, -S(O)¿tR?11 (wherein t is 0, 1 or 2), -SCN, -N(R10)2, -NR?10R11, -NO¿2, -OC(O)R10, -CO2R10, -OCO¿2R?11, -CN, -NHC(O)R10, -NHSO¿2R?10, -CONHR10, -CONHCH¿2?CH2OH, -NR?10COOR11, -SR11C(O)OR11, -SR11N(R75)2¿; n is 0 (zero), 1, 2, 3, 4, 5 or 6; T is -CO-; -SO-; -SO¿2?-; or -CR?30R31¿-; Z represents alkyl, aryl, aralkyl, heteroalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, -OR?40, -SR40, -CR40R42, -NR40R42¿, formulae (i), (ii), (iii), (iv), (v) and (vi). Pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel tricyclic compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human.

公开(公告)号：EP0819121A1

公开(公告)日：1998-01-21

申请号：EP96912469.0

申请日：1996-04-03

申请人： SCHERING CORPORATION ,  PHARMACOPEIA, INC.

发明人： AFONSO, Adriano ,  BALDWIN, John, J. ,  DOLL, Ronald, J. ,  LI, Ge ,  MALLAMS, Alan, K. ,  NJOROGE, F., George ,  RANE, Dinanath, F. ,  READER, John, C. ,  ROSSMAN, Randall, R.

IPC分类号： A61K31 ,  A61P35 ,  A61P43 ,  C07D221 ,  C07D401 ,  C07D491

CPC分类号： C07D401/04 ,  C07D221/16 ,  C07D401/12 ,  C07D491/04

摘要： Novel compounds of Formula (1.0) are disclosed. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering a compound of formula (1.0) to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human being.

公开(公告)号：EP1551818B1

公开(公告)日：2009-02-04

申请号：EP03781311.0

申请日：2003-10-07

申请人： Schering Corporation ,  Pharmacopeia, Inc.

发明人： TAVERAS, Arthur, G. ,  CHAO, Jianhua ,  BIJU, Purakkattle, J. ,  YU, Younong ,  FINE, Jay, S. ,  HIPKIN, William ,  AKI, Cynthia, J. ,  MERRITT, J., Robert ,  LI, Ge ,  BALDWIN, John, J. ,  LAI, Gaifa ,  WU, Minglang ,  HECKER, Evan, A.

IPC分类号： C07D285/10 ,  C07D417/12 ,  C07D417/14 ,  A61K31/433 ,  A61K31/4436

CPC分类号： C07D285/10 ,  C07D417/02 ,  C07D417/12 ,  C07D417/14

摘要： Disclosed are novel compounds of the formula (IA) and the pharmaceutically acceptable salts and solvates thereof. Examples of groups comprising Substituent A include heteroaryl, aryl, heterocycloalkyl, cycloalkyl, aryl, alkynyl, alkenyl, aminoalkyl, alkyl or amino. Examples of groups comprising Substituent B include aryl and heteroaryl. Also disclosed is a method of treating a chemokine mediated diseases, such as, cancer, angiogenisis, angiogenic ocular diseases, pulmonary diseases, multiple sclerosis, rheumatoid arthritis, osteoarthritis, stroke and cardiac reperfusion injury, acute pain, acute and chronic inflammatory pain, and neuropathic pain using a compound of formula (IA).

公开(公告)号：EP1313725B1

公开(公告)日：2007-04-11

申请号：EP01968188.1

申请日：2001-08-28

申请人： SCHERING CORPORATION ,  Pharmacopeia Drug Discovery, Inc.

发明人： NJOROGE, F., George ,  VIBULBHAN, Bancha ,  COOPER, Alan, B. ,  GUZI, Timothy ,  RANE, Dinanath, F. ,  MINOR, Keith, P. ,  DOLL, Ronald, J. ,  GIRIJAVALLABHAN, Viyyoor, Moopil ,  SANTHANAM, Bama ,  PINTO, Patrick, A. ,  ZHU, Hugh, Y. ,  KEERTIKAR, Kartik, M. ,  ALVAREZ, Carmen, S. ,  BALDWIN, John, J. ,  LI, Ge ,  HUANG, Chia-Yu ,  JAMES, Ray, A. ,  BISHOP, Robert, W. ,  WANG, James ,  DESAI, Jagdish, A.

IPC分类号： C07D401/06 ,  C07D401/04 ,  C07D401/14 ,  C07D221/16 ,  A61K31/435 ,  A61P35/00

CPC分类号： C07D231/12 ,  C07D221/16 ,  C07D233/56 ,  C07D249/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/14

摘要： The present invention discloses novel tricyclic compounds represented by the formula (1.0), a prodrug thereof, or a pharmaceutically acceptable salt or solvate of the compound or of said prodrug useful for inhibiting farnesyl protein transferase. Also disclosed are pharmaceutical compositions comprising such compounds their preparation as well as methods of using them to treat proliferative diseases such as cancer.

公开(公告)号：EP0931078B1

公开(公告)日：2006-11-15

申请号：EP97941477.8

申请日：1997-09-11

申请人： SCHERING CORPORATION

发明人： COOLER, Alan, B. ,  MALLANS, Alan, K. ,  GIRIJAVALLABHAN, Viyyoor, M. ,  DOLL, Ronald, J. ,  TAVERAS, Arthur, G. ,  NJOROGE,, F., George ,  BALDWIN, John, J. ,  READER, John, C.

IPC分类号： C07D401/14 ,  C07F9/6558 ,  C07H19/04 ,  C07D401/04 ,  A61K31/435

CPC分类号： C07D401/14 ,  C07D401/04 ,  C07F9/591 ,  C07F9/65583

摘要： Novel tricyclic compounds of formula (1.0) or a pharmaceutically acceptable salt or solvate thereof, wherein: one of a, b, c, and d represents N or NR9, wherein R9 is O-, -CH¿3? or -(CH2)nCO2H wherein n is 1 to 3, and the remaining a, b, c and d groups represent CR?1 or CR2¿; or each of a, b, c and d is independently selected from CR?1 or CR2¿; each R1 and each R2 is independently selected from H, halo, -CR¿3?, -OR?10, -COR10, -SR10¿, -S(O)¿tR?11 (wherein t is 0, 1 or 2), -SCN, -N(R10)2, -NR?10R11, -NO¿2, -OC(O)R10, -CO2R10, -OCO¿2R?11, -CN, -NHC(O)R10, -NHSO¿2R?10, -CONHR10, -CONHCH¿2?CH2OH, -NR?10COOR11, -SR11C(O)OR11, -SR11N(R75)2¿; n is 0 (zero), 1, 2, 3, 4, 5 or 6; T is -CO-; -SO-; -SO¿2?-; or -CR?30R31¿-; Z represents alkyl, aryl, aralkyl, heteroalkyl, heteroaryl, heteroarylalkyl, heterocycloalkyl, heterocycloalkylalkyl, -OR?40, -SR40, -CR40R42, -NR40R42¿, formulae (i), (ii), (iii), (iv), (v) and (vi). Pharmaceutical compositions are disclosed which are inhibitors of the enzyme, farnesyl protein transferase. Also disclosed is a method of inhibiting Ras function and therefore inhibiting the abnormal growth of cells. The method comprises administering the novel tricyclic compound to a biological system. In particular, the method inhibits the abnormal growth of cells in a mammal such as a human.