公开(公告)号：US20040266780A1

公开(公告)日：2004-12-30

申请号：US10697912

申请日：2003-10-30

发明人： Chanchal Sadhu ,  Ken Dick ,  Jennifer Treiberg ,  C. Gregory Sowell ,  Edward A. Kesicki ,  Amy Oliver

IPC分类号： A61K031/497 ,  A61K031/501 ,  A61K031/506 ,  A61K031/4709

CPC分类号： A61K31/506 ,  C07D403/12 ,  C07D473/00 ,  C07D473/16 ,  C07D473/24 ,  C07D473/30 ,  C07D473/32 ,  C07D473/34 ,  C07D473/38 ,  C07D473/40 ,  C07D487/04 ,  C12N9/1205 ,  C12N9/99 ,  C12Y207/01137

摘要： Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3Knull) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3Knull plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3Knull, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3Knull activity, including compounds that selectively inhibit PI3Knull activity. Methods of using PI3Knull inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3Knull inhibitory compounds to inhibit PI3Knull-mediated processes in vitro and in vivo.

摘要翻译： 公开了抑制磷脂酰肌醇3-激酶δ同种型（PI3Kdelta）活性的方法，以及治疗PI3Kdelta在白细胞功能中起作用的疾病如免疫和炎症疾病的方法。 优选地，所述方法使用选择性抑制PI3Kdelta的活性剂，而不显着抑制其它PI3K同种型的活性。 提供抑制PI3Kdelta活性的化合物，包括选择性抑制PI3Kdelta活性的化合物。 还提供了使用PI3Kdelta抑制化合物抑制癌细胞生长或增殖的方法。 因此，本发明提供了使用PI3Kdelta抑制化合物在体外和体内抑制PI3Kdelta介导的过程的方法。

公开(公告)号：US20040259879A1

公开(公告)日：2004-12-23

申请号：US10893520

申请日：2004-07-16

发明人： Hengmaio Cheng ,  Subas Man Sakya ,  Jason Kenneth Dutra

IPC分类号： C07D43/02 ,  A61K031/501 ,  A61K031/4439

CPC分类号： C07D401/04 ,  C07D231/24 ,  C07D401/14

摘要： The present invention relates to compounds of the formula 1 wherein R1, R2, R3, R4, R5, R6, R7, R8, A, X and Y are defined as in the specification, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the invention are useful in the treatment or alleviation of inflammation and other inflammation associated disorders, such as arthritis, colon cancer, and Alzheimer's disease in mammals, preferably humans, dogs, cats and livestock animals.

摘要翻译： 本发明涉及下式的化合物其中R 1，R 2，R 3，R 4，R 5，R 6，R 7，R 8， A，X和Y在说明书中定义为含有它们的药物组合物及其药用用途。 本发明的化合物可用于治疗或缓解哺乳动物，优选人，狗，猫和家畜中的炎症和其它炎症相关疾病，例如关节炎，结肠癌和阿尔茨海默病。

公开(公告)号：US20040235852A1

公开(公告)日：2004-11-25

申请号：US10850231

申请日：2004-05-19

发明人： Alan G. Olivero ,  Daniel P. Sutherlin

IPC分类号： A61K031/501 ,  A61K031/443 ,  A61K031/343

CPC分类号： C07D405/12 ,  C07D307/81

摘要： Compounds of Formula I are useful for inhibiting serine protease enzymes, such as TF/factor VIIa, factor Xa, thrombin and kallikrein and have improved pharmacokinetic properties. These compounds may be used in methods of preventing and/or treating clotting disorders. 1

摘要翻译： 式I的化合物可用于抑制丝氨酸蛋白酶，例如TF /因子VIIa，因子Xa，凝血酶和激肽释放酶，并具有改善的药代动力学性质。 这些化合物可用于预防和/或治疗凝血障碍的方法。

公开(公告)号：US20040229875A1

公开(公告)日：2004-11-18

申请号：US10770814

申请日：2004-02-03

发明人： Jingrong Cao ,  Jeremy Green ,  Michael Hale ,  Francois Maltais ,  Judy Straub ,  Qing Tang ,  Alex Aronov

IPC分类号： A61K031/53 ,  A61K031/501 ,  A61K031/497

CPC分类号： C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14

摘要： Described herein are compounds that are useful as protein kinase inhibitors having the formula: 1 wherein Z1 and Z2 are each independently nitrogen or CH and Ring A, TmR1, QR2, UnR3, and Sp are as described in the specification. The compounds are especially useful as inhibitors of ERK2 and for treating diseases in mammals that are alleviated by a protein kinase inhibitor, particularly diseases such as cancer, inflammatory disorders, restenosis, diabetes, and cardiovascular disease.

摘要翻译： 本文描述了可用作具有下式的蛋白激酶抑制剂的化合物：其中Z 1和Z 2各自独立地为氮或CH，环A，TmR 1，Q 2，R un R 3， 和Sp如说明书中所述。 该化合物特别可用作ERK2的抑制剂，并且用于治疗由蛋白激酶抑制剂，特别是癌症，炎性疾病，再狭窄，糖尿病和心血管疾病等疾病缓解的哺乳动物疾病。

公开(公告)号：US20040198739A1

公开(公告)日：2004-10-07

申请号：US10485636

申请日：2004-02-03

发明人： Jerome Emile Georges Guillemont ,  Patrice Palandjian ,  Marc Rene de Jonge ,  Lucien Maria Henricus Koymans ,  Hendrik Maarten Vinkers ,  Frederik Frans Desire Daeyaert ,  Jan Heeres ,  Koen Jeanne Alfons Van Aken ,  Paulus Joannes Lewi ,  Paul Adriaan Jan Janssen

IPC分类号： A61K031/506 ,  A61K031/501 ,  C07D43/14

CPC分类号： C07D239/48 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/551 ,  A61K45/06 ,  C07C255/42 ,  C07C257/12 ,  C07D239/47 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12

摘要： This invention concerns HIV replication inhibitors of formula (I) the N-oxides, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, wherein the ring containing -a1nulla2-a3nulla4- and -b1nullb2-b3nullb4- represents pheynl, pyridyl, pyrimidinyl, pirazinyl, pyridazinyl;n is 0 to 5; m is 1 to 4; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; C1-6alkyl; C1-6alkyloxycarbonyl, substituted C1-6alkyl, C1-6alkylcarbonyl; R2 is hydroxy, halo, optionally substituted C1-6alkyl, C3-7cycloalkyl, optionally substituted C2-6alkenyl, optionally substituted C2-6alkynyl, C1-6alkyloxy, C1-6alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C1-6alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, nullS(nullO)pR6, nullNHnullS(nullO)pR6, nullC(nullO)R6, nullNHC(nullO)H, nullC(nullO)NHNHnull2null, nullNHC(nullO)R6, nullC(nullNH)R6 or a 5-membered hetrocycl; X1 is nullNR5null, nullNHnullNHnull, nullNnullNnull, nullOnull, nullC(nullO)null, C1-4alkanediyl, nullCHOHnull, nullSnull, nullS(nullO)pnull, nullX2nullC1-4alkanediyl- or nullC1-4alkanediyl-X2null; R3 is NHR13, NR13R14; nullC(nullO)nullNHR13; nullC(nullO)nullNR13R14; nullC(nullO)nullR15; nullCHnullNnullNHnullC(nullO)nullR16; substituted C1-6alkyl; optionally substituted C1-6alkyloxyC1-6alkyl; substituted C2-6alkenyl; substituted C2-6alkynyl; substituted C2-6alkylenyl; C1-6alkyl substituted with hydroxy and a second substituent; nullC(nullNnullOnullR8)nullC1-4alkyl; R7; or nullX3nullR7; R4 is halo, hydroxy, C1-6alkyl, C3-7cycloalkyl, C1-6alkyloxy, cyano, nitro, polyhaloC1-6alkyl, polyhaloC1-6alkyloxy, aminocarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonyl, formyl, amino, mono- or di(C1-4alkyl) amino; their use as a medicine, their processes for preparation and pharmaceutical compositions comprising them. 1

摘要翻译： 本发明涉及式（I）的N-复合抑制剂，其N-氧化物，药学上可接受的加成盐，季胺及其立体化学异构形式，其中含-a 1 = a 2 -a 3 n = 0〜5; b 1 = b 2 -b 3 = b 4 - 表示吡啶基，吡啶基，嘧啶基，吡嗪基，哒嗪基; n为0〜5; m为1〜4; R 1是氢; 芳基; 甲酰基 C 1-6烷基羰基; C 1-6烷基; C 1-6烷氧基羰基，取代的C 1-6烷基，C 1-6烷基羰基; R 2是羟基，卤素，任选取代的C 1-6烷基，C 3-7环烷基，任选取代的C 2-6烯基，任选取代的C 2-6炔基，C 1-6烷氧基，C 1-6烷氧基羰基，羧基，氰基，硝基，氨基，单或 （C 1-6烷基）氨基，多卤甲基，多卤代甲氧基，多卤甲硫基，-S（= O）pR 6，-NH-S（= O）p R 6，-C（= O）R 6， NHC（= O）H，-C（= O）NHNH 2，-NHC（= O）R 6，-C（= NH）R 6或5元环庚烯; X1是-NR5 - ， - NH-NH-，-N = N-，-O - ， - C（= O） - ，C1-4烷二基，-CHOH-，-S-，-S（= O ）p-，-X2-C1-4烷二基或-C1-4烷二基X2-; R 3是NHR 13，NR 13 R 14; -C（= O）-NHR 13; -C（= O）-NR 13 R 14; -C（= O）-R 15; -CH = N-NH-C（= O）-R 16; 取代的C 1-6烷基; 任选取代的C 1-6烷氧基C 1-6烷基; 取代的C 2-6烯基; 取代的C 2-6炔基; 取代的C2-6亚烷基; C

公开(公告)号：US20040198730A1

公开(公告)日：2004-10-07

申请号：US10488577

申请日：2004-03-04

发明人： David Kenneth Dean ,  Andrew Kenneth Takle ,  David Matthew Wilson

IPC分类号： A61K031/53 ,  A61K031/501 ,  C07D43/04

CPC分类号： C07D401/04 ,  A61K31/44 ,  A61K31/505 ,  C07D405/04

摘要： Compounds and their use as pharmaceuticals particularly as Raf kinase inhibitors for the treatment of neurotraumatic diseases, cancer, chronic neurodegeneration, pain, migraine and cardiac hypertrophy.

摘要翻译： 化合物及其作为药物的用途，特别是用作治疗神经创伤性疾病，癌症，慢性神经变性，疼痛，偏头痛和心脏肥大的Raf激酶抑制剂。

公开(公告)号：US20040192730A1

公开(公告)日：2004-09-30

申请号：US10799490

申请日：2004-03-12

申请人： Dynogen Pharmaceuticals, Inc.

发明人： Karl Bruce Thor

IPC分类号： A61K031/4545 ,  A61K031/506 ,  A61K031/501

CPC分类号： A61K31/437 ,  A61K31/40 ,  A61K31/404 ,  A61K31/4245 ,  A61K31/4365 ,  A61K31/4545 ,  A61K31/46 ,  A61K31/496 ,  A61K31/538

摘要： A method is provided for using compounds that exhibit combined activities as 5-HT1A active agents and selective serotonin reuptake inhibitors (SSRI's) to treat sexual dysfunction, particularly premature ejaculation, on an as-needed basis shortly before sexual activity.

摘要翻译： 提供了一种使用化合物作为5-HT1A活性剂和选择性5-羟色胺再摄取抑制剂（SSRI's）的化合物在性活动前不久就根据需要治疗性功能障碍，特别是早泄的方法。

公开(公告)号：US20040192689A1

公开(公告)日：2004-09-30

申请号：US10488578

申请日：2004-03-04

发明人： David Kenneth Dean ,  Andrew Kenneth Takle ,  David Matthew Wilson

IPC分类号： A61K031/53 ,  A61K031/501 ,  A61K031/497 ,  A61K031/4439 ,  C07D49/02 ,  C07D43/02

CPC分类号： C07D405/04

摘要： Compounds and their use as pharmaceuticals particularly as Raf kinase inhibitors for the treatment of neurotraumatic diseases, cancer, chronic neurodegeneration, pain, migraine or cardiac hypertrophy.

摘要翻译： 化合物及其作为药物的用途，特别是用作治疗神经创伤性疾病，癌症，慢性神经变性，疼痛，偏头痛或心脏肥大的Raf激酶抑制剂。

公开(公告)号：US20040176377A1

公开(公告)日：2004-09-09

申请号：US10715358

申请日：2003-11-19

发明人： Swen Holder ,  Thorsten Naumann ,  Karl Schonafinger ,  David William Will ,  Hans Matter ,  Gunther Muller ,  Dominique Le Suisse ,  Bernard Baudoin ,  Thomas Rooney ,  Franck Halley ,  Gilles Tiraboschi

IPC分类号： A61K031/501 ,  A61K031/50 ,  C07D43/02

CPC分类号： C07D401/04 ,  C07D237/14 ,  C07D237/24 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D405/04 ,  C07D405/14 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/14 ,  C07D513/04

摘要： The present invention relates to novel pyridazinone derivatives of the general formula (I) 1 wherein A is A1 or A2; 2 R is unsubstituted or at least monosubstituted C1-C10-alkyl, aryl, aryl-(C1-C10-alkyl)-, heteroaryl, heteroaryl-(C1-C10-alkyl)-, heterocyclyl, heterocyclyl-(C1-C10-alkyl)-, C3-C10-cycloalkyl, polycycloalkyl, C2-C10-alkenyl or C2-C10-alkinyl and Ar is unsubstituted or at least monosubstituted aryl or heteroaryl.

摘要翻译： 本发明涉及通式（I）的新的哒嗪酮衍生物，其中A为A 1或A 2; R是未取代的或至少单取代的C 1 -C 10 - 烷基，芳基，芳基 - （C 1 -C 10 - 烷基） - ，杂芳基，杂芳基 - （C 1 -C 10 - 烷基） - ，杂环基，杂环基 - （C 1 -C 10 - 烷基） C 3 -C 10 - 环烷基，多环烷基，C 2 -C 10 - 烯基或C 2 -C 10 - 炔基，Ar是未取代的或至少单取代的芳基或杂芳基。

公开(公告)号：US20040147516A1

公开(公告)日：2004-07-29

申请号：US10757525

申请日：2004-01-15

申请人： Kowa Co., Ltd.

发明人： Masao Ohkuchi ,  Yoshinori Kyotani ,  Hiromichi Shigyo ,  Tomoyuki Koshi ,  Takahiro Kitamura ,  Tadaaki Ohgiya ,  Takayuki Matsuda ,  Yukiyoshi Yamazaki ,  Natsuyo Kumai ,  Kyoko Kotaki ,  Hideo Yoshizaki ,  Yuriko Habata

IPC分类号： A61K031/501 ,  C07D43/02

CPC分类号： C07D401/04 ,  C07D237/02 ,  C07D237/04 ,  C07D237/14 ,  C07D237/18 ,  C07D401/06 ,  C07D401/14 ,  C07D413/04

摘要： This invention relates to pyridazine derivatives represented by the formula (1): 1 wherein R1 represents a (substituted) aryl group, R2 represents a phenyl group substituted at 4-position by a lower alkoxyl group or a lower alkylthio group, R3 represents a lower alkoxyl group, a halogenated lower alkyl group, a lower cycloalkyl group, a (subsituted) aryl group, a (substituted) aryloxy group, a (substituted) nitrogen-containing heterocyclic ring residue, a (substituted) aminocarbonyl group or a lower alkylcarbonyl group, A represents a single bond, a lower alkylene group or a lower alkenylene group, X represents O or S, and the dashed line indicates that the carbon-carbon bond between the 4-position and the 5-position is a single bond or a double bond, or salts thereof; and also to medicines containing them as effective ingredients. These compounds have excellent inhibitory activity against interleukin-1null production, and are useful as preventives and therapeutics for immune system diseases, inflammatory diseases, ischemic diseases and the like.

摘要翻译： 本发明涉及由式（1）表示的哒嗪衍生物：其中R 1表示（取代的）芳基，R 2表示在4-位被低级烷氧基或低级烷硫基取代的苯基 R 3表示低级烷氧基，卤代低级烷基，低级环烷基，（取代的）芳基，（取代的）芳氧基，（取代的）含氮杂环残基，（取代的） ）氨基羰基或低级烷基羰基，A表示单键，低级亚烷基或低级亚烯基，X表示O或S，虚线表示4-位和5位之间的碳 - 碳键 - 位是单键或双键，或其盐; 以及含有它们作为有效成分的药物。 这些化合物对白细胞介素-1β生产具有优异的抑制活性，可用作免疫系统疾病，炎性疾病，缺血性疾病等的预防药物和治疗剂。