公开(公告)号：US20050038069A1

公开(公告)日：2005-02-17

申请号：US10933077

申请日：2004-09-01

申请人： Paul Cox ,  Shelley Bower ,  David Aldous ,  Peter Astles ,  Daniel McGarry ,  Christopher Hulme ,  John Regan ,  Fu-Chih Huang ,  Stevan Djuric ,  Kevin Moriarty ,  Rose Mathew ,  Gregory Poli

发明人： Paul Cox ,  Shelley Bower ,  David Aldous ,  Peter Astles ,  Daniel McGarry ,  Christopher Hulme ,  John Regan ,  Fu-Chih Huang ,  Stevan Djuric ,  Kevin Moriarty ,  Rose Mathew ,  Gregory Poli

IPC分类号： C07D235/08 ,  A61K31/00 ,  A61K31/40 ,  A61K31/403 ,  A61K31/404 ,  A61K31/41 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/4184 ,  A61K31/4196 ,  A61K31/42 ,  A61K31/422 ,  A61K31/44 ,  A61K31/4427 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4439 ,  A61K31/47 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/505 ,  A61K31/506 ,  A61K31/535 ,  A61K31/5355 ,  A61K31/5375 ,  A61K31/5377 ,  A61P9/00 ,  A61P11/00 ,  A61P17/00 ,  A61P25/04 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P43/00 ,  C07D209/08 ,  C07D209/12 ,  C07D209/42 ,  C07D235/12 ,  C07D235/24 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14 ,  C07D217/12

CPC分类号： C07D235/24 ,  C07D209/12 ,  C07D209/42 ,  C07D401/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/14

摘要： This invention is directed to physiologically active compounds of formula (I) wherein represents a bicyclic ring system, of about 10 to about 13 ring members, in which the ring is an azaheterocycle, and the ring represents an azaheteroaryl ring, or an optionally halo substituted benzene ring; R1 represents hydrogen or a straight- or branched-chain alkyl group of 1 to about 4 carbon atoms, optionally substituted by hydroxy or one or more halogen atoms, or when Z1 represents a direct bond R1 may also represent a lower alkenyl or lower alkynyl group, or a formyl group; R2 represents hydrogen, alkenyl, alkoxy, alkyl, alkylsulphinyl, alkylsulphonyl, alkylthio, aryl, arylalkyloxy, arylalkylsulphinyl, arylalkylsulphonyl, arylalkylthio, aryloxy, arylsulphinyl, arylsulphonyl, arylthio, cyano, cycloalkenyl, cycloalkenyloxy, cycloalkyl, cycloalkyloxy, heteroaryl, heteroarylalkyloxy, heteroaryloxy, hydroxy, —SO2NR4R5, —NR4SO2R5, —NR4R5, —C(═O)R5, —C(═O)C(═O)R5, —C(═O)NR4R5, —C(═O)OR5, —O(C═O)NR4R5, or —NR4C(═O)R5; R3 represents —C(=Z)—N(R7)R6, —C(=Z)—CHR12R6, —C(=Z)—R6, —CR8═C(R9)(CH2)p—R6, —C(R10)═C(R11)R12, —C(R13)(R10)C(R11)(R14)R12, —C(R8)(R15)CH(R9)(CH2)p—R6, —R6, —N(R16)C(=Z)R6, —C(R17)═N—OC(=0)R18, —C(═O)—N(R19)OR20, —C≡C—R6, —CH2—C(=Z)—R6, —C(=Z)—C(=Z)R6, —CH2—NHR6, —CH2-ZR6, —CH2—SOR6, —CH2—SO2R6, —CF2—OR6, —NH—CH2R6, -Z-CH2R6, —SO—CH2R6, —SO2—CH2R6, —O—CF2R6, —O—C(=Z)R6, —N═N—R6, —NH—SO2R6, —SO2—NR21R22, —CZ-CZ-NHR6, —NH—CO—OR6, —O—CO—NHR6, —NH—CO—NHR6, —R23, —CX1═CX2R6, —C(═NOR24), —(CH2)qR6, —CH2—CO—NH(CH2)qR6, —CH2—NH—CO(CH2)qR6, —CH2—CO—CH2R6, —C(═NR25)—NH(CH2)qR6, —C(X3)═N—(CH2)qR6 or —CH(X4)—CH2R6; A1 represents a direct bond, or a straight or branched C1-6 alkylene chain optionally substituted by hydroxyl, alkoxy, oxo, cycloalkyl, aryl or heteroaryl, or A1 represents a straight or branched C2-6alkenylene or C2-6alkynylene chain; Z1 represents a direct bond, an oxygen or sulphur atom or NH; n and m each represent zero or 1, provided that n is 1 when m is zero and n is zero when m is 1; and N-oxides thereof, and their prodrugs, and pharmaceutically acceptable salts and solvates of the compounds of formula (I) and N-oxides thereof, and their prodrugs. Such compounds inhibit the production or physiological effects of TNF and inhibit cyclic AMP phosphodiesterase. The invention is also directed to pharmaceutical compositions comprising compounds of formula (I), their pharmaceutical use and methods for their preparation.

摘要翻译： 本发明涉及式（I）的生理活性化合物，其中代表双环体系，约10至约13个环成员，其中该环是氮杂环，并且该环代表氮杂杂芳基环，或任选地被卤素取代 苯环; R 1表示氢或1至约4个碳原子的直链或支链烷基，任选被羟基或一个或多个卤素原子取代，或当Z 1表示直接键R 1时 也代表低级烯基或低级炔基或甲酰基; R 2表示氢，烯基，烷氧基，烷基，烷基亚磺酰基，烷基磺酰基，烷硫基，芳基，芳基烷氧基，芳基烷基亚磺酰基，芳基烷基磺酰基，芳基烷硫基，芳氧基，芳基亚磺酰基，芳基磺酰基，芳硫基，氰基，环烯基，环烯氧基，环烷基，环烷氧基，杂芳基， ，杂芳氧基，羟基，-SO 2 NR 4 R 5，-NR 4 SO 2 R 5，-NR 4 R 5，-C（= O）R 5，-C（= O）C（= O）R 5，-C（= O）NR 4 R 5，-C（= O）OR 5，-O（C = O）NR 4 R 5或-NR 4 C（= O）R 5; R 3表示-C（= Z）-N（R 7）R 6，-C（= Z）-CHR 12 R 6，-C（= Z）-R 6 ，-CR 8 = C（R 9）（CH 2）p R 6，-C（R 10）= C（R 11）R 12，-C（R 13） （R 10）C（R 11）（R 14）R 12，-C（R 8）（R 15）CH（R 9）（CH 2） pR 6，-R 6，-N（R 16）C（= Z）R 6，-C（R 17）= N-OC（= O）R 18， -C（= O）-N（R <19）

公开(公告)号：US20070060502A1

公开(公告)日：2007-03-15

申请号：US11552346

申请日：2006-10-24

申请人： Yong Choi-Sledeski ,  Julian Levell ,  Gregory Poli ,  Mark Czekaj ,  Alan Collis ,  Roy Vaz

发明人： Yong Choi-Sledeski ,  Julian Levell ,  Gregory Poli ,  Mark Czekaj ,  Alan Collis ,  Roy Vaz

IPC分类号： A61K38/16 ,  C07K5/06

CPC分类号： C07K5/0827 ,  A61K38/00 ,  C07F9/301 ,  C07F9/303 ,  C07F9/572 ,  C07F9/5728 ,  C07F9/65031 ,  C07F9/6506 ,  C07K5/06191

摘要： The present invention relates to a series of substituted 3-aminopropane phosphinic acid derivatives of formula I: wherein R, R1, P1, P2 and P3 are as defined herein. The compounds of this invention are useful in treating a variety of diseases including but not limited to depression, anxiety, certain psychiatric symptoms, cognitive impairment and schizophrenia.

摘要翻译： 本发明涉及一系列式I的取代的3-氨基丙烷次膦酸衍生物：其中R 1，R 1，P 1，P 2， >和P 3 <3>如本文所定义。 本发明的化合物可用于治疗各种疾病，包括但不限于抑郁，焦虑，某些精神症状，认知障碍和精神分裂症。