公开(公告)号：US20060111370A1

公开(公告)日：2006-05-25

申请号：US11149027

申请日：2005-06-09

申请人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

发明人： Zhaoning Zhu ,  Brian McKittrick ,  Zhong-Yue Sun ,  Yuanzan Ye ,  Johannes Voigt ,  Corey Strickland ,  Elizabeth Smith ,  Andrew Stamford ,  William Greenlee ,  Robert Mazzola ,  John Caldwell ,  Jared Cumming ,  Lingyan Wang ,  Yusheng Wu ,  Ulrich Iserloh ,  Tao Guo ,  Thuy Le ,  Kurt Saionz ,  Suresh Babu ,  Rachael Hunter ,  Michelle Morris ,  Huizhong Gu ,  Gang Qian ,  Dawit Tadesse

IPC分类号： A61K31/519 ,  A61K31/497 ,  A61K31/513 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/4245 ,  C07D413/02 ,  C07D403/02

CPC分类号： C07D233/46 ,  C07D233/70 ,  C07D233/88 ,  C07D239/22 ,  C07D239/70 ,  C07D271/07 ,  C07D273/00 ,  C07D401/04 ,  C07D401/08 ,  C07D401/10 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/08 ,  C07D403/10 ,  C07D403/12 ,  C07D405/10 ,  C07D409/04 ,  C07D409/10 ,  C07D409/14 ,  C07D413/10 ,  C07D413/12 ,  C07D417/06

摘要： Disclosed are compounds of the formula I or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein W is a bond, —C(═S)—, —S(O)—, —S(O)2—, —C(═O)—, —O—, —C(R6)(R7)—, —N(R5)— or —C(═N(R5))—; X is —O—, —N(R5)— or —C(R6)(R7)—; provided that when X is —O—, U is not —O—, —S(O)—, —S(O)2—, —C(═O)— or —C(═NR5)—; U is a bond, —S(O)—, —S(O)2—, —C(O)—, —O—, —P(O)(OR15)—, —C(═NR5)—, —(C(R6)(R7))b— or —N(R5)—; wherein b is 1 or 2; provided that when W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, U is not —S(O)—, —S(O)2—, —O—, or —N(R5)—; provided that when X is —N(R5)— and W is —S(O)—, —S(O)2—, —O—, or —N(R5)—, then U is not a bond; and R1, R2, R3, R4, R5, R6, and R7 are as defined in the specification; and pharmaceutical compositions comprising the compounds of formula I. Also disclosed is the method of inhibiting aspartyl protease, and in particular, the methods of treating cardiovascular diseases, cognitive and neurodegenerative diseases, and the methods of inhibiting of Human Immunodeficiency Virus, plasmepins, cathepsin D and protozoal enzymes. Also disclosed are methods of treating cognitive or neurodegenerative diseases using the compounds of formula I in combination with a cholinesterase inhibitor or a muscarinic m1 agonist or m2 antagonist.

公开(公告)号：US07022731B2

公开(公告)日：2006-04-04

申请号：US10759396

申请日：2004-01-15

申请人： Robert M. Scarborough ,  Hans-Michael Jantzen ,  Wolin Huang ,  David M. Sedlock ,  Charles Marlowe

发明人： Robert M. Scarborough ,  Hans-Michael Jantzen ,  Wolin Huang ,  David M. Sedlock ,  Charles Marlowe

IPC分类号： C07D409/12 ,  A61K31/4025 ,  A61P7/02

CPC分类号： C07D239/22 ,  C07D239/48 ,  C07D239/50 ,  C07D333/34 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D495/04

摘要： Novel compounds of formula (I) to (VI), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I)–(VI), or a pharmaceutically acceptable salt thereof.

公开(公告)号：US06906063B2

公开(公告)日：2005-06-14

申请号：US09920325

申请日：2001-08-02

申请人： Robert M. Scarborough ,  Wolin Huang ,  Charles K. Marlowe ,  Kim A. Kane-MaGuire

发明人： Robert M. Scarborough ,  Wolin Huang ,  Charles K. Marlowe ,  Kim A. Kane-MaGuire

IPC分类号： C07D239/96 ,  A61K31/16 ,  A61K31/175 ,  A61K31/381 ,  A61K31/4196 ,  A61K31/4725 ,  A61K31/519 ,  A61K31/54 ,  A61K31/64 ,  A61P7/02 ,  A61P9/00 ,  A61P9/04 ,  A61P9/10 ,  A61P9/14 ,  A61P43/00 ,  C07D209/48 ,  C07D213/70 ,  C07D239/22 ,  C07D239/50 ,  C07D333/34 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D487/04 ,  C07D495/04 ,  C07D521/00 ,  A61K31/40 ,  C07D411/12 ,  C07D417/14

CPC分类号： C07D487/04 ,  C07D209/48 ,  C07D239/22 ,  C07D239/48 ,  C07D239/50 ,  C07D239/96 ,  C07D333/34 ,  C07D333/62 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D495/04 ,  C07D521/00

摘要： Novel compounds of formulae (I) to (VIII), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I) to (VIII), or a pharmaceutically acceptable salt thereof.

摘要翻译： 式（I）至（VIII）的新型化合物，其更具体地包括作为有效的血小板ADP受体抑制剂的磺酰脲衍生物，磺酰基硫脲衍生物，磺酰基胍衍生物，磺酰氰基胍衍生物，硫代酰基磺酰胺衍生物和酰基磺酰胺衍生物。 这些衍生物可用于各种药物组合物中，并且对于预防和/或治疗心血管疾病，特别是与血栓形成有关的疾病特别有效。 本发明还涉及一种用于预防或治疗哺乳动物血栓形成的方法，包括施用治疗有效量的式（I）至（VIII）化合物或其药学上可接受的盐的步骤。

公开(公告)号：US20040147576A1

公开(公告)日：2004-07-29

申请号：US10759396

申请日：2004-01-15

申请人： Portola Pharmaceuticals, Inc.

发明人： Robert M. Scarborough ,  Hans-Michael Jantzen ,  Wolin Huang ,  David M. Sedlock ,  Charles Marlowe

IPC分类号： A61K031/44 ,  A61K031/4196 ,  A61K031/175 ,  A61K031/18

CPC分类号： C07D239/22 ,  C07D239/48 ,  C07D239/50 ,  C07D333/34 ,  C07D401/04 ,  C07D401/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D417/12 ,  C07D495/04

摘要： Novel compounds of formula (I) to (VI), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I)-(VI), or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20040147400A1

公开(公告)日：2004-07-29

申请号：US10476941

申请日：2003-11-06

发明人： Jorn Stolting ,  Dorothee Hoischen ,  Roland Andree ,  Karl-Heinz Linker ,  Holger Weintritt ,  Heinz-Jurgen Wroblowsky

IPC分类号： A01N043/54 ,  C07D239/02

CPC分类号： C07D239/22 ,  C07D239/54

摘要： The present invention relates to a novel process for preparing known 1-amino-3-phenyluracil derivatives (1-amino-3-phenyl-2,4(1H,3H)pyrimidinedione derivatives) and novel 1-amino-6-hydroxy-3-phenyldihydro-2,4(1H,3H)pyrimidinedione derivatives of the formula (II) 1 in which R1 is hydrogen, cyano, nitro or halogen, R2 is cyano, nitro, halogen or optionally substituted alkyl or alkoxy, R3 is hydrogen, hydroxyl, mercapto, amino, hydroxyamino, hydrazino, halogen, or one of the radicals nullR6, -Q-R6, nullNHnullR6, nullNHnullOnullR6, nullNHnullSO2nullR6, nullN(SO2nullR6)2, nullCQ1-R6, nullCQ1-Q2-R6, nullCQ1-NHnullR6, -Q2-CQ1-R6, nullNHnullCQ1-R6, N(SO2nullR6)(CQ1-R6), -Q2-CQ1-Q2-R6, nullNHnullCQ1-Q2-R6 or -Q2-CQ1-NHnullR6, where Q is O, S, SO or SO2, Q1 and Q2 are each independently oxygen or sulphur and R6 is optionally substituted alkyl, alkenyl, alkinyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl, R4 is hydrogen, halogen or optionally substituted alkyl, and R5 is fluorine- and/or chlorine-substituted alkyl, as intermediates therefor and to a process for preparing them.

公开(公告)号：US20040138242A1

公开(公告)日：2004-07-15

申请号：US10702579

申请日：2003-11-06

申请人： Merck and Co., Inc. ,  Synaptic Pharmaceutical Corporation

发明人： Donghui Cui ,  Margaret R. Davis ,  Michael Dunn ,  Ben E. Evans ,  Hanumath P. Kari ,  Bharat Lagu ,  Dhanapalan Nagarathnam ,  Kamlesh P. Vyas ,  Kanyin Zhang

IPC分类号： A61K031/513 ,  C07D239/02

CPC分类号： C07D239/22 ,  C07D401/12 ,  C07D401/14 ,  C07D491/04

摘要： This invention is directed to dihydropyrimidines which are selective antagonists for human null1a receptors. This invention is also related to uses of these compounds for relaxing lower urinary tract tissue, treating benign prostatic hyperplasia and for the treatment of any disease where the antagonism of the null1a receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

摘要翻译： 本发明涉及作为人α1a受体的选择性拮抗剂的二氢嘧啶。 本发明还涉及这些化合物用于缓解下尿路组织，治疗良性前列腺增生和用于治疗α1a受体的拮抗作用可能有用的任何疾病的用途。 本发明还提供了包含治疗有效量的上述化合物和药学上可接受的载体的药物组合物。

公开(公告)号：US06696451B1

公开(公告)日：2004-02-24

申请号：US09673592

申请日：2000-10-18

申请人： Jürgen Stoltefuss ,  Siegfired Goldmann ,  Thomas Krämer ,  Karl-Heinz Schlemmer ,  Ulrich Niewöhner ,  Arnold Paessens ,  Erwin Graef ,  Stefan Lettmann ,  Karl Deres ,  Olaf Weber ,  Jörn Stölting

发明人： Jürgen Stoltefuss ,  Siegfired Goldmann ,  Thomas Krämer ,  Karl-Heinz Schlemmer ,  Ulrich Niewöhner ,  Arnold Paessens ,  Erwin Graef ,  Stefan Lettmann ,  Karl Deres ,  Olaf Weber ,  Jörn Stölting

IPC分类号： C07D40104

CPC分类号： C07D239/22 ,  C07D213/78 ,  C07D213/84 ,  C07D401/04 ,  C07D401/14

摘要： The invention relates to compounds of the general formulae (I) and (Ia) The invention furthermore relates to processes for preparing the compounds of the formulae (I) and (Ia) and to their use as medicaments, in particular for the treatment and prophylaxis of hepatitis B.

摘要翻译： 本发明涉及通式（I）和（Ia）的化合物。本发明还涉及制备式（I）和（Ia）化合物的方法及其作为药物的用途，特别是用于治疗和预防 的乙型肝炎

公开(公告)号：US20030166690A1

公开(公告)日：2003-09-04

申请号：US10319212

申请日：2002-12-13

发明人： Soren Ebdrup ,  Johannes Cornelis de Jong ,  Poul Jacobsen ,  Holger Claus Hansen ,  Per Vedso

IPC分类号： A61K031/455 ,  A61K031/401 ,  A61K031/275 ,  A61K031/16

CPC分类号： C07D207/404 ,  C07C39/367 ,  C07C233/25 ,  C07C233/26 ,  C07C233/60 ,  C07C307/06 ,  C07C311/04 ,  C07C311/17 ,  C07C311/21 ,  C07C311/29 ,  C07C311/40 ,  C07C317/22 ,  C07C323/20 ,  C07C2601/14 ,  C07D209/08 ,  C07D209/32 ,  C07D209/48 ,  C07D211/88 ,  C07D213/61 ,  C07D213/63 ,  C07D213/64 ,  C07D213/643 ,  C07D213/68 ,  C07D213/69 ,  C07D213/70 ,  C07D213/74 ,  C07D213/75 ,  C07D213/84 ,  C07D215/20 ,  C07D215/22 ,  C07D217/24 ,  C07D231/12 ,  C07D231/16 ,  C07D233/54 ,  C07D233/56 ,  C07D235/18 ,  C07D235/26 ,  C07D237/14 ,  C07D239/22 ,  C07D241/18 ,  C07D241/44 ,  C07D249/04 ,  C07D249/08 ,  C07D249/18 ,  C07D253/04 ,  C07D257/04 ,  C07D261/12 ,  C07D263/52 ,  C07D277/24 ,  C07D277/68 ,  C07D285/01 ,  C07D295/205 ,  C07D295/26 ,  C07D307/16 ,  C07D307/52 ,  C07D307/89 ,  C07D311/16 ,  C07D311/18 ,  C07D333/16 ,  C07D333/32 ,  C07D401/04 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/04 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07D471/06 ,  C07D491/10

摘要： Use of compounds to inhibit hormone-sensitive lipase, pharmaceutical compositions comprising the compounds, methods of treatment employing these compounds and compositions, and novel compounds. The present compounds are inhibitors of hormone-sensitive lipase and may be useful in the treatment and/or prevention of medical disorders where a decreased activity of hormone-sensitive lipase is desirable.

摘要翻译： 使用化合物抑制激素敏感性脂肪酶，包含化合物的药物组合物，使用这些化合物和组合物的治疗方法以及新化合物。 本发明化合物是激素敏感性脂肪酶的抑制剂，并且可用于治疗和/或预防需要激素敏感性脂肪酶活性降低的医学病症。

公开(公告)号：US20030069222A1

公开(公告)日：2003-04-10

申请号：US10094790

申请日：2002-03-08

申请人： Vertex Pharmaceuticals, Inc.

发明人： Roger D. Tung ,  Mark A. Murcko ,  Govinda R. Bhisetti

IPC分类号： A61K031/553 ,  A61K031/554 ,  A61K031/55 ,  A61K031/54 ,  A61K031/535 ,  A61K031/445

CPC分类号： C07D207/26 ,  A61K38/00 ,  C07C307/06 ,  C07C311/13 ,  C07C311/18 ,  C07C311/29 ,  C07C311/39 ,  C07C311/46 ,  C07C2601/02 ,  C07C2601/08 ,  C07C2601/14 ,  C07D209/08 ,  C07D213/30 ,  C07D213/78 ,  C07D215/38 ,  C07D215/48 ,  C07D231/14 ,  C07D239/22 ,  C07D263/24 ,  C07D271/08 ,  C07D277/36 ,  C07D307/12 ,  C07D307/20 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07K5/06139

摘要： The present invention relates to a novel class of sulfonamides which are aspartyl protease inhibitors. In one embodiment, this invention relates to a novel class of HIV aspartyl protease inhibitors characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HIV-1 and HIV-2 protease activity and consequently, may be advantageously used as anti-viral agents against the HIV-1 and HIV-2 viruses. This invention also relates to methods for inhibiting the activity of HIV aspartyl protease using the compounds of this invention and methods for screening compounds for anti-HIV activity.

摘要翻译： 本发明涉及一类新型的磺酰胺，它们是天冬氨酰蛋白酶抑制剂。 在一个实施方案中，本发明涉及以特定结构和物理化学特征为特征的新型HIV天冬氨酰蛋白酶抑制剂。 本发明还涉及包含这些化合物的药物组合物。 本发明的化合物和药物组合物特别适用于抑制HIV-1和HIV-2蛋白酶活性，因此可有利地用作针对HIV-1和HIV-2病毒的抗病毒剂。 本发明还涉及使用本发明化合物抑制HIV天冬氨酰蛋白酶活性的方法和用于筛选抗HIV活性化合物的方法。

公开(公告)号：US06545006B1

公开(公告)日：2003-04-08

申请号：US09581142

申请日：2000-12-11

申请人： Ulrike Milbert ,  Robert Bartlett ,  Eric Ruuth ,  Claude Fudali

发明人： Ulrike Milbert ,  Robert Bartlett ,  Eric Ruuth ,  Claude Fudali

IPC分类号： A61K31505

CPC分类号： C07D239/22 ,  B01J41/20 ,  G01N30/02 ,  G01N30/32 ,  G01N2030/8831 ,  B01D15/363

摘要： The invention relates to a process for obtaining L-dihydroorotic acid by chromatography on an anionic exchange material in a base water mixture under a pressure from about 1.1 MPa to about 40 MPa. The process can be used to investigate the in vitro and in vivo activity of N-(4-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide, N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxycrontonamide and similar compounds.

摘要翻译： 本发明涉及一种在约1.1MPa至约40MPa的压力下通过基础水混合物中的阴离子交换材料的色谱法获得L-二氢乳酸的方法。 该方法可用于研究N-（4-三氟甲基苯基）-5-甲基异恶唑-4-甲酰胺，N-（4-三氟甲基苯基）-2-氰基-3-羟基克罗宁酰胺和类似化合物的体外和体内活性。