公开(公告)号：WO2009077448A1

公开(公告)日：2009-06-25

申请号：PCT/EP2008/067412

申请日：2008-12-12

Applicant: NOVARTIS AG ,  ABRAMS, Tinya ,  BARSANTI, Paul ,  DUHL, David ,  FAURE, Michel ,  RENHOWE, Paul A. ,  WALTER, Annette Olga

Inventor： ABRAMS, Tinya ,  BARSANTI, Paul ,  DUHL, David ,  FAURE, Michel ,  RENHOWE, Paul A. ,  WALTER, Annette Olga

IPC: A61K31/4164 ,  C07D233/00 ,  A61P35/00

CPC classification number: A61K31/4164 ,  C07D233/61

Abstract: The invention provides novel imidazole compounds that inhibit the activity of kinesin spindle protein (KSP, also called Eg5). Inhibitors of KSP can reduce undesired cellular proliferation and provide other therapeutic effects. The invention also provides pharmaceutical compositions containing these novel compounds, and methods of using the novel KSP inhibitors and their pharmaceutical compositions to treat various types of cancers. The compounds, compositions and methods of the invention are especially useful for treating certain classes of cancers that are resistant to conventional drug treatments, because such cancers are shown to remain sensitive to the compounds of the invention.

Abstract translation: 本发明提供抑制驱动蛋白纺锤体蛋白（KSP，也称为Eg5）的活性的新型咪唑化合物。 KSP抑制剂可以减少不希望的细胞增殖并提供其他治疗效果。 本发明还提供含有这些新化合物的药物组合物，以及使用新型KSP抑制剂及其药物组合物治疗各种类型癌症的方法。 本发明的化合物，组合物和方法特别可用于治疗对常规药物治疗有抗性的某些类型的癌症，因为这些癌症显示出对本发明化合物的敏感性。

公开(公告)号：WO2003072056A3

公开(公告)日：2003-09-04

申请号：PCT/US2003/005874

申请日：2003-02-25

Applicant: CHIRON CORPORATION ,  XIAO, Linda, Li ,  XU, Baoji ,  LUO, Jian ,  JOHNSON, Kirk ,  FREY, William, H., II ,  TOZZO, Effie ,  DUHL, David

Inventor： XIAO, Linda, Li ,  XU, Baoji ,  LUO, Jian ,  JOHNSON, Kirk ,  FREY, William, H., II ,  TOZZO, Effie ,  DUHL, David

IPC: A61K38/00

Abstract: A method for delivering a melanocortin-4 receptor agonist to a mammalian subject, includes administering the melanocortin-4 receptor agonist to a tissue inside the nasal cavity or sinuses of the mammalian subject. In some instances, the melanocortin-4 receptor agonist includes a guanidine functional group.

公开(公告)号：WO2011128381A1

公开(公告)日：2011-10-20

申请号：PCT/EP2011/055840

申请日：2011-04-13

Applicant: NOVARTIS AG ,  ABRAMS, Tinya ,  BARSANTI, Paul, A. ,  DING, Yu ,  DUHL, David ,  HAN, Wooseok ,  HU, Cheng ,  PAN, Yue

Inventor： ABRAMS, Tinya ,  BARSANTI, Paul, A. ,  DING, Yu ,  DUHL, David ,  HAN, Wooseok ,  HU, Cheng ,  PAN, Yue

IPC: C07D249/08 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  A61P35/00 ,  A61K31/55

CPC classification number: C07D403/12 ,  A61K31/4196 ,  A61K31/5377 ,  A61K45/06 ,  C07D207/10 ,  C07D249/08 ,  C07D405/12 ,  C07D405/14 ,  C07D413/14

Abstract: The present invention provides triazole compounds of Formula (I) : as further described herein. The invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), and a method of treating a disorder mediated, at least in part, by KSP in a mammalian patient comprising administering to a mammalian patient in need of such treatment a therapeutically effective amount of a compound of Formula (I).

Abstract translation: 本发明提供式（I）的三唑化合物：如本文进一步描述的。 本发明还提供了包含治疗有效量的式（I）化合物的药物组合物，以及治疗哺乳动物患者至少部分地由KSP介导的病症的方法，包括向需要的哺乳动物患者施用 治疗有效量的式（I）化合物。

公开(公告)号：WO2002081443A1

公开(公告)日：2002-10-17

申请号：PCT/US2002/010965

申请日：2002-04-08

Applicant: CHIRON CORPORATION ,  CHU, Daniel ,  BOYCE, Rustum, S. ,  DUHL, David ,  CHANG, Bryan

Inventor： CHU, Daniel ,  BOYCE, Rustum, S. ,  DUHL, David ,  CHANG, Bryan

IPC: C07D209/02

CPC classification number: C07D209/46 ,  C07D209/48 ,  C07D217/24 ,  C07D235/08 ,  C07D235/10

Abstract: Compounds having he general structure I are provided. X and Y are independently selected from the group consisting of CH 2 , N, NR 9 , C=O, C=S, S=O, SO 2 , S, O, (CR 6 R 7 ) n , C(=O)-(CR 6 R 7 ) n , and C(=S)-(CR 6 R 7 ) n , where n is 1, 2, or 3. W is selected from the group consisting of (formula I) and L is selected from the group consisting of N, O, S=O, SO 2 , C(O), NC(O), NC(S), OC(O), OC(S), C(NR 10 ), C(NOR 10 ), and a covalent bond. Z 1 , Z 2 , and Z 3 are independently selected from the group consisting of substituted carbon and nitrogen. Compounds of formula I are agonists of the melanocortin-4 receptor ("MC-4r2) and therefore may have useful properties for controlling diseases related to MC-4r action in humans, such as obesity and type II diabetes.

Abstract translation: 提供具有一般结构I的化合物。 X和Y独立地选自CH 2，N，NR 9，C = O，C = S，S = O，SO 2，S，O，（CR 6 R 7） C（= O） - （CR 6 R 7）n和C（= S） - （CR 6 R 7）n，其中n是1,2或3.选择W 由式（I）和L组成的组选自由N，O，S = O，SO 2，C（O），NC（O），NC（S），OC（O） S），C（NR 10），C（NOR 10）和共价键。 Z 1，Z 2和Z 3独立地选自取代的碳和氮。 式I化合物是黑皮质素-4受体（“MC-4r2”）的激动剂，因此可能具有控制人类MC-4r作用相关疾病如肥胖和II型糖尿病的有用性质。

公开(公告)号：WO9708317A3

公开(公告)日：1997-09-25

申请号：PCT/US9613974

申请日：1996-08-29

Applicant: DUHL DAVID ,  CHIRON CORP

Inventor： DUHL DAVID

IPC: C07K14/72 ,  C12N15/12 ,  C07K16/28 ,  C12N5/10 ,  C12Q1/68 ,  G01N33/50 ,  G01N33/68

CPC classification number: C07K14/723 ,  C07K2319/00 ,  C12N2799/026 ,  G01N2333/726 ,  G01N2500/00

Abstract: A new human hypothalmic receptor has been identified, and the amino acid and nucleotide sequence of the receptor are provided. The nucleotide sequence is useful to construct expression cassettes and vectors to produce host cells which are capable of expressing the receptor, its mutants, fragments, or fusions. Such polypeptides are useful for identifying new agonists and antagonists.

公开(公告)号：WO2008063912A1

公开(公告)日：2008-05-29

申请号：PCT/US2007/084154

申请日：2007-11-08

Applicant: NOVARTIS AG ,  XIA, Yi ,  MENDENHALL, Kris G. ,  BARSANTI, Paul A. ,  WALTER, Annette O. ,  DUHL, David ,  RENHOWE, Paul A.

Inventor： XIA, Yi ,  MENDENHALL, Kris G. ,  BARSANTI, Paul A. ,  WALTER, Annette O. ,  DUHL, David ,  RENHOWE, Paul A.

IPC: C07D249/08 ,  C07D401/12 ,  C07D403/12 ,  C07D413/12 ,  A61K31/55 ,  A61P35/00

CPC classification number: C07D401/12 ,  C07D249/08 ,  C07D403/12 ,  C07D413/12

Abstract: Disclosed are new substituted pyrazole and triazole compounds of Formula (I) and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the derivatives together with pharmaceutically acceptable carriers, and uses thereof:

Abstract translation: 公开了式（I）的新的取代的吡唑和三唑化合物及其药学上可接受的盐，酯或前药，衍生物的组合物和药学上可接受的载体，及其用途：

公开(公告)号：WO2006002236A1

公开(公告)日：2006-01-05

申请号：PCT/US2005/022062

申请日：2005-06-20

Applicant: CHIRON CORPORATION ,  WANG, Weibo ,  BARSANTI, Paul, A. ,  XI, Yi ,  BOYCE, Rustum, S. ,  PECCHI, Sabina ,  BRAMMEIER, Nathan ,  PHILLIPS, Megan ,  MENDENHALL, Kris ,  WAYMAN, Kelly ,  LAGNITON, Liana, Marie ,  CONSTANTINE, Ryan ,  YANG, Hong ,  MIEULI, Elizabeth ,  RAMURTHY, Savithri ,  JAZAN, Elisa ,  SHARMA, Anu ,  RAMA, Jain ,  SABRAMANIAN, Sharadha ,  RENHOWE, Paul ,  BAIR, Kenneth, Walter ,  DUHL, David ,  WALTER, Annette ,  ABRAMS, Tinya ,  HUH, Kay ,  MARTIN, Eric ,  KNAPP, Mark ,  LE, Vincent

Inventor： WANG, Weibo ,  BARSANTI, Paul, A. ,  XI, Yi ,  BOYCE, Rustum, S. ,  PECCHI, Sabina ,  BRAMMEIER, Nathan ,  PHILLIPS, Megan ,  MENDENHALL, Kris ,  WAYMAN, Kelly ,  LAGNITON, Liana, Marie ,  CONSTANTINE, Ryan ,  YANG, Hong ,  MIEULI, Elizabeth ,  RAMURTHY, Savithri ,  JAZAN, Elisa ,  SHARMA, Anu ,  RAMA, Jain ,  SABRAMANIAN, Sharadha ,  RENHOWE, Paul ,  BAIR, Kenneth, Walter ,  DUHL, David ,  WALTER, Annette ,  ABRAMS, Tinya ,  HUH, Kay ,  MARTIN, Eric ,  KNAPP, Mark ,  LE, Vincent

IPC: C07D233/54

CPC classification number: C07D233/54 ,  C07D233/24 ,  C07D233/64 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D403/14 ,  C07D405/06 ,  C07D405/12 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/04 ,  C07D417/06 ,  C07D417/12 ,  C07D417/14 ,  C07D498/10

Abstract: This invention is directed to substituted imidazole compounds which modulate the activity of KSP and are useful for the treatment of cancer and are represented by the formula (I) wherein: R 1 is selected from the group consisting of aminoacyl, acylamino, carboxyl, carboxyl ester, aryl, and alkyl optionally substituted with hydroxy or halo; R 2 is selected from the group consisting of hydrogen, alkyl, and aryl; R 3 is selected from the group consisting of hydrogen and -X-A, wherein X is selected from the group consisting of-C(O)-, -C(S)-, -S(O)-, -S(O) 2 -, and -S(O)2-N(R)-, where R is hydrogen or alkyl; and A is selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, carboxyl, carboxyl ester, aminoacyl, optionally substituted heteroaryl, optionally substituted heterocyclic, and optionally substituted cycloalkyl, wherein the optionally substituted groups are substituted with 1 to 4 substituents; R 5 is selected from the group consisting of L-A 1 , wherein L is selected from the group consisting of-S(O) q - where q is one or two, and C 1 to C 5 alkylene optionally substituted with hydroxy, halo, or acylamino; and A 1 is selected from the group consisting of aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, substituted heterocyclic, cycloalkyl, and substituted cycloalkyl; and one of either R 6 or R 7 is selected from the group consisting of heterocyclic, aryl and heteroaryl, all of which may be optionally substituted with -(R 8 ) m where R 8 is as defined herein and m is an integer from 1 to 3, and the other Of R 6 or R 7 is selected from the group consisting of hydrogen, halo, and alkyl; or R 6 and R 7 are both hydrogen; the other substituents are defined in the claims.

Abstract translation: 本发明涉及调节KSP活性并且可用于治疗癌症并由式（I）表示的取代的咪唑化合物，其中：R 1选自氨基酰基 酰基氨基，羧基，羧基酯，芳基和任选被羟基或卤素取代的烷基; R 2选自氢，烷基和芳基; R 3选自氢和-XA，其中X选自-C（O） - ， - C（S） - ， - S（O） - ，-S（O）2 - 和-S（O）2 -N（R） - ，其中R是氢或烷基; 并且A选自氢，任选取代的烷基，任选取代的烷氧基，任选取代的芳基，羧基，羧基酯，氨酰基，任选取代的杂芳基，任选取代的杂环和任选取代的环烷基，其中任选取代的基团被取代 具有1至4个取代基; R 5选自LA 1，其中L选自-S（O）q - ，其中 q是一个或两个，并且C 1至C 5亚烷基，其任选被羟基，卤素或酰基氨基取代; 并且A 1选自芳基，取代的芳基，杂芳基，取代的杂芳基，杂环，取代的杂环，环烷基和取代的环烷基; 且R 6或R 7中的一个选自杂环，芳基和杂芳基，其全部可以任选地被 - （R' 其中R 8如本文所定义，m是1至3的整数，R 6中的另一个 或R 7选自氢，卤素和烷基; 或R 6和R 7都是氢; 其它取代基在权利要求中限定。

公开(公告)号：WO1997046680A1

公开(公告)日：1997-12-11

申请号：PCT/US1997009715

申请日：1997-06-04

Applicant: CHIRON CORPORATION ,  DUHL, David

Inventor： CHIRON CORPORATION

IPC: C12N15/12

CPC classification number: C07K14/4702 ,  A61K48/00 ,  C12N2799/021

Abstract: The present invention is a novel nucleic acid sequence which hybridizes to SEQ ID NO:6 or fragments thereof under stringent conditions, or fragments thereof. The invention also includes diagnostic assays, expression vectors, control sequences, antisense molecules, ribozymes, and host cells to express the polypeptide encoded by the nucleic acid sequence. The present invention also includes claims to the polypeptide sequence coded by the nucleic acid sequences.

Abstract translation: 本发明是在严格条件下与SEQ ID NO：6或其片段杂交的新型核酸序列或其片段。 本发明还包括诊断测定，表达载体，控制序列，反义分子，核酶和宿主细胞，以表达由核酸序列编码的多肽。 本发明还包括由核酸序列编码的多肽序列的权利要求。

公开(公告)号：WO1997008317A2

公开(公告)日：1997-03-06

申请号：PCT/US1996013974

申请日：1996-08-29

Applicant: CHIRON CORPORATION ,  DUHL, David

Inventor： CHIRON CORPORATION

IPC: C12N15/12

CPC classification number: C07K14/723 ,  C07K2319/00 ,  C12N2799/026 ,  G01N2333/726 ,  G01N2500/00

Abstract: A new human hypothalmic receptor has been identified, and the amino acid and nucleotide sequence of the receptor are provided. The nucleotide sequence is useful to construct expression cassettes and vectors to produce host cells which are capable of expressing the receptor, its mutants, fragments, or fusions. Such polypeptides are useful for identifying new agonists and antagonists.

Abstract translation: 已经鉴定了新的人类下丘脑受体，并提供了受体的氨基酸和核苷酸序列。 核苷酸序列可用于构建表达盒和载体以产生能够表达受体，其突变体，片段或融合物的宿主细胞。 这些多肽可用于鉴定新的激动剂和拮抗剂。

公开(公告)号：WO2007021794A1

公开(公告)日：2007-02-22

申请号：PCT/US2006/031129

申请日：2006-08-09

Applicant: NOVARTIS AG ,  BARSANTI, Paul A. ,  XIA, Yi ,  WANG, Weibo ,  MENDENHALL, Kris G. ,  LAGNITON, Liana M. ,  RAMURTHY, Savithri ,  PHILLIPS, Megan C. ,  SUBRAMANIAN, Sharadha ,  BOYCE, Rustum ,  BRAMMEIER, Nathan M. ,  CONSTANTINE, Ryan ,  DUHL, David ,  WALTER, Annette O. ,  ABRAMS, Tinya J. ,  RENHOWE, Paul A.

Inventor： BARSANTI, Paul A. ,  XIA, Yi ,  WANG, Weibo ,  MENDENHALL, Kris G. ,  LAGNITON, Liana M. ,  RAMURTHY, Savithri ,  PHILLIPS, Megan C. ,  SUBRAMANIAN, Sharadha ,  BOYCE, Rustum ,  BRAMMEIER, Nathan M. ,  CONSTANTINE, Ryan ,  DUHL, David ,  WALTER, Annette O. ,  ABRAMS, Tinya J. ,  RENHOWE, Paul A.

IPC: C07D401/14 ,  C07D233/54 ,  C07D403/12 ,  C07D403/06 ,  C07D409/12 ,  C07D413/12 ,  C07D407/12 ,  A61K31/4178 ,  A61K31/4545 ,  A61P35/00

CPC classification number: C07D401/14 ,  C07D233/64 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12

Abstract: The present invention relates to new substituted imidazole compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the derivatives together with pharmaceutically acceptable carriers, and uses of the compounds. The compounds of the invention have the following general formula (I).

Abstract translation: 本发明涉及新的取代的咪唑化合物及其药学上可接受的盐，酯或前药，衍生物的组合物和药学上可接受的载体，以及该化合物的用途。 本发明的化合物具有以下通式（I）。