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：US20170226146A1

公开(公告)日：2017-08-10

申请号：US15427674

申请日：2017-02-08

申请人： John Y.L. Chung ,  Amude Kassim ,  John Limanto ,  Michael Shevlin ,  Peter E. Maligres ,  Daniel A. DiRocco ,  James F. Dropinski ,  Rose Mathew ,  Yi Ning Ji Chen ,  Edward C. Sherer ,  Mikhail Reibarkh ,  Artis Klapars ,  Alan Hyde ,  Susan L. Zultanski ,  Aaron Moment ,  Bryon Simmons ,  Tyler A. Davis ,  Timothy James Wright ,  Ralph Calabria ,  Louis Charles Campeau

发明人： John Y.L. Chung ,  Amude Kassim ,  John Limanto ,  Michael Shevlin ,  Peter E. Maligres ,  Daniel A. DiRocco ,  James F. Dropinski ,  Rose Mathew ,  Yi Ning Ji Chen ,  Edward C. Sherer ,  Mikhail Reibarkh ,  Artis Klapars ,  Alan Hyde ,  Susan L. Zultanski ,  Aaron Moment ,  Bryon Simmons ,  Tyler A. Davis ,  Timothy James Wright ,  Ralph Calabria ,  Louis Charles Campeau

IPC分类号： C07H19/10 ,  C07H19/24 ,  C07D487/04 ,  C07H19/06

CPC分类号： C07H19/10 ,  C07D487/04 ,  C07H19/06 ,  C07H19/24

摘要： The present invention is directed to a process for making Chloro-Substituted Nucleoside Phosphoramidate Compounds of formula (I): which are useful for the treatment and prophylaxis of HCV infection. The present invention is also directed to compounds that are useful as synthetic intermediates for making the compounds of formula (I).

公开(公告)号：US20070265278A1

公开(公告)日：2007-11-15

申请号：US11782890

申请日：2007-07-25

申请人： Keith HARRIS ,  Hans-Jochen Lang ,  Rose Mathew ,  Stephen Shimshock ,  Thaddeus Nieduzak ,  Sharon Jackson ,  Zhaoxia Yang ,  Kenneth Bordeau

发明人： Keith HARRIS ,  Hans-Jochen Lang ,  Rose Mathew ,  Stephen Shimshock ,  Thaddeus Nieduzak ,  Sharon Jackson ,  Zhaoxia Yang ,  Kenneth Bordeau

IPC分类号： A61K31/404 ,  A61K31/4245 ,  A61K31/435 ,  A61K31/4453 ,  A61K31/47 ,  A61K31/495 ,  A61P1/04 ,  A61P37/08 ,  A61P9/00 ,  C07D209/04 ,  C07D271/113 ,  C07D401/12

CPC分类号： C07D209/12 ,  C07D209/18 ,  C07D209/22 ,  C07D209/24 ,  C07D405/12 ,  C07D413/06

摘要： The present invention is directed to a compound of Formula (XVI): (please replace Formula (I) with Formula (XVI) as shown below) wherein R, R2, R3, R4, R5, R6, R7 and n are as defined herein, or a pharmaceutically acceptable salt, hydrate, or solvate thereof, a pharmaceutically acceptable prodrug thereof, or a pharmaceutically acceptable salt, hydrate or solvate of the prodrug, a pharmaceutical composition comprising a pharmaceutically effective amount of one or more compounds according to Formula (XVI) in admixture with a pharmaceutically acceptable carrier, a method of treating a patient suffering from a PGD2-mediated disorder including, but not limited to, allergic disease (such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma and food allergy), systemic mastocytosis, disorders accompanied by systemic mast cell activation, anaphylaxis shock, bronchoconstriction, bronchitis, urticaria, eczema, diseases accompanied by itch (such as atopic dermatitis and urticaria), diseases (such as cataract, retinal detachment, inflammation, infection and sleeping disorders) which are generated secondarily as a result of behavior accompanied by itch (such as scratching and beating), inflammation, chronic obstructive pulmonary diseases, ischemic reperfusion injury, cerebrovascular accident, chronic rheumatoid arthritis, pleurisy, ulcerative colitis and the like by administering to said patient a pharmaceutically effective amount of a compound according to Formula (XVI).

摘要翻译： 本发明涉及式（ⅩⅥ）化合物：（如下所示，用式（ⅩⅥ）表示的式（I）表示）其中R，R 2，R 3， R 4，R 4，R 5，R 6，R 7和n如本文所定义，或 其药学上可接受的盐，水合物或溶剂化物，其药学上可接受的前药，或药学上可接受的盐，水合物或溶剂化物，药物组合物，其包含药学上有效量的根据式（XVI）的一种或多种化合物 与药学上可接受的载体混合，治疗患有PGD2介导的病症的患者的方法，包括但不限于过敏性疾病（例如过敏性鼻炎，过敏性结膜炎，特应性皮炎，支气管哮喘和食物过敏），全身肥大细胞增多症 ，伴有系统性肥大细胞活化，过敏性休克，支气管收缩，支气管炎，荨麻疹， 湿疹，伴有瘙痒的疾病（如特应性皮炎和荨麻疹），伴随瘙痒的行为（如刮伤和殴打）而产生的疾病（如白内障，视网膜脱离，炎症，感染和睡眠障碍） ，炎症，慢性阻塞性肺疾病，缺血再灌注损伤，脑血管意外，慢性类风湿性关节炎，胸膜炎，溃疡性结肠炎等，通过向所述患者施用药学有效量的根据式（XVI）的化合物。