公开(公告)号：US07354928B2

公开(公告)日：2008-04-08

申请号：US10286085

申请日：2002-11-01

Applicant: Shaomeng Wang ,  Dajun Yang ,  Istvan J. Enyedy

Inventor： Shaomeng Wang ,  Dajun Yang ,  Istvan J. Enyedy

IPC: A61K31/44 ,  A61K31/335 ,  A61K31/135 ,  A61K31/505 ,  A61K31/65

CPC classification number: A61K45/06 ,  A61K31/00 ,  A61K31/122 ,  A61K31/395 ,  A61K31/404 ,  A61K31/4184 ,  A61K31/444 ,  A61K31/452 ,  A61K31/473 ,  A61K31/4745 ,  A61K31/519 ,  A61K31/655 ,  A61K2300/00

Abstract: The present invention relates to small molecule antagonists of Bcl-2 family proteins such as Bcl-2 and/or Bcl-XL. In particular, the present invention provides non-peptide cell permeable small molecules (e.g., tricyclo-dibenzo-diazocine-dioxides) that bind to a pocket in Bcl-2/Bcl-XL that block the anti-apoptotic function of these proteins in cancer cells and tumor tissues exhibiting Bcl-2 protein overexpression. In preferred embodiments, the small molecules of the present invention are active at the BH3 binding pocket of Bcl-2 family proteins (e.g., Bcl-2, Bcl-XL, and Mcl-1). The compositions and methods of the present invention are useful therapeutics for cancerous diseases either alone or in combination with chemotherapeutic or other drugs.

Abstract translation: 本发明涉及Bcl-2家族蛋白质如Bcl-2和/或Bcl-X L的小分子拮抗剂。 特别地，本发明提供了结合Bcl-2 / Bcl-XLL中的口袋的非肽细胞可渗透的小分子（例如三环二苯并二氮杂二恶英），其阻断抗 这些蛋白在癌细胞和表达Bcl-2蛋白过表达的肿瘤组织中的凋亡功能。 在优选的实施方案中，本发明的小分子在Bcl-2家族蛋白（例如Bcl-2，Bcl-X L和Mcl-1）的BH3结合口袋上是有活性的。 本发明的组合物和方法单独或与化学治疗剂或其它药物组合用于癌性疾病的有用治疗剂。

公开(公告)号：US07342046B2

公开(公告)日：2008-03-11

申请号：US11089096

申请日：2005-03-24

Applicant: Shaomeng Wang ,  Jiangyong Chen

Inventor： Shaomeng Wang ,  Jiangyong Chen

IPC: A61K31/225 ,  A61K31/11 ,  A61K31/70

CPC classification number: A61K31/11

Abstract: This invention relates to compositions comprising co-crystals of (−)-gossypol with a C1-8 carboxylic acid or C1-8 sulfonic acid which are useful as inhibitors of Bcl-2 family proteins. The invention also relates to the use of co-crystals of (−)-gossypol with a C1-8 carboxylic acid or C1-8 sulfonic acid for inducing apoptosis in cells and for sensitizing cells to the induction of apoptotic cell death.

公开(公告)号：US20050131051A1

公开(公告)日：2005-06-16

申请号：US10362164

申请日：2001-08-21

Applicant: Shaomeng Wang ,  Sukumar Sakamuri ,  Istvan Enyedey ,  Alan Kozikowski

Inventor： Shaomeng Wang ,  Sukumar Sakamuri ,  Istvan Enyedey ,  Alan Kozikowski

IPC: C07D453/02 ,  A61K31/407 ,  A61K31/439 ,  A61K39/00 ,  A61K47/48 ,  A61P25/00 ,  A61P25/04 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P25/28 ,  A61P25/32 ,  A61P25/36 ,  A61P43/00 ,  C07B57/00 ,  C07D211/52 ,  C07D487/04 ,  C07D491/04

CPC classification number: C07D491/04 ,  C07D211/52 ,  C07D453/02

Abstract: The present invention relates to a class of compounds of formula (I) and (II): wherein R1 is hydrogen; linear or branched C1-C15 alkyl; C1-C15 alkenyl; C3-C6 cycloalkyl; mono, di, tri, tetra, penta substituted aryl or heteroaryl; COOR3; —(CH2)n-aryl; —COO—(CH2)nR3; —(CH2)n—COOR3; —C(O)R3; —C(O)NHR3; or an unsubstituted or substituted oxadiazole; and R2 is hydrogen; linear or branched C1-C15 alkyl; C1-C15 alkenyl; C3-C6 cycloalkyl; mono, di, tri, tetra, penta substituted aryl or heteroaryl; unsubstituted or substituted naphthyl; 1,3-Benzodioxole; fluorene; indole; isoquinoline; quinoline; pyridine; pyrimidine; onnthracene; or —(CH2)n-Ph; wherein the heteroaryl comprises N, O, or S, the mono or multi substituents on the aryl or heteroaryl are independently C1-C5 alkyl, C1-C5 alkenyl, H, F, Cl, Br, I, —NO2, NHR, or —OR, R is C1-C7 alkyl; R3 is C1-C5 alkyl, C1-C5 alkenyl, benzyl, substituted aryl or heteroaryl; and n=1-7. These compounds are discovered, synthesized and confirmed as potent inhibitors of dopamine (DA), serotonin (5-HT), and norepinephrine inhibitors. These compounds are therefore particularly useful in the treatment conditions or diseases wherein modulation of the monoamine neurotransmitter system involving dopamine (DA), serotonin (5-HT), and norepinephrine plays a role.

公开(公告)号：US08557812B2

公开(公告)日：2013-10-15

申请号：US11209998

申请日：2005-08-22

Applicant: Shaomeng Wang ,  Guoping Wang ,  Guozhi Tang ,  Renxiao Wang ,  Zaneta Nikolovska-Coleska ,  Dajun Yang ,  Liang Xu

Inventor： Shaomeng Wang ,  Guoping Wang ,  Guozhi Tang ,  Renxiao Wang ,  Zaneta Nikolovska-Coleska ,  Dajun Yang ,  Liang Xu

IPC: C07D401/02 ,  A61K31/47

CPC classification number: C07C205/38 ,  C07C39/10 ,  C07C39/15 ,  C07C39/17 ,  C07C39/367 ,  C07C43/23 ,  C07C43/295 ,  C07C49/747 ,  C07C49/82 ,  C07C49/83 ,  C07C49/84 ,  C07C65/105 ,  C07C235/60 ,  C07C235/64 ,  C07C311/29 ,  C07C311/46 ,  C07C317/22 ,  C07C317/40 ,  C07C317/44 ,  C07C2601/14 ,  C07C2603/74 ,  C07D211/16 ,  C07D213/70 ,  C07D215/227 ,  C07D215/233 ,  C07D217/06 ,  C07D263/56 ,  C07D277/64 ,  C07D307/84 ,  C07D321/12 ,  C07D333/60 ,  C07D333/76 ,  C07D401/12 ,  C07D405/12

Abstract: The invention relates to small molecules which function as inhibitors of anti-apoptotic Bcl-2 family member proteins (e.g., Bcl-2 and Bcl-xL). The invention also relates to the use of these compounds for inducing apoptotic cell death and sensitizing cells to the induction of apoptotic cell death.

Abstract translation: 本发明涉及作为抗凋亡Bcl-2家族成员蛋白（例如Bcl-2和Bcl-xL）的抑制剂的小分子。 本发明还涉及这些化合物用于诱导凋亡细胞死亡和使细胞对诱导凋亡性细胞死亡致敏的用途。

公开(公告)号：US20120263675A1

公开(公告)日：2012-10-18

申请号：US13503366

申请日：2010-10-20

Applicant: Shaomeng Wang ,  Haiying Sun

Inventor： Shaomeng Wang ,  Haiying Sun

IPC: A61K31/4184 ,  A61K31/437 ,  A61K31/52 ,  A61K31/423 ,  A61K31/428 ,  A61K31/427 ,  C12N5/071 ,  A61K38/19 ,  A61K38/17 ,  A61K39/395 ,  A61P35/00 ,  A61P27/02 ,  A61P29/00 ,  A61P19/02 ,  A61P17/06 ,  A61P9/10 ,  A61P27/06 ,  A61P9/00 ,  A61P1/00 ,  A61P17/00 ,  A61P17/02 ,  A61M37/00 ,  C07D487/04

CPC classification number: C07D519/00 ,  C07D487/04

Abstract: The invention relates to diazo bicyclic Smac mimetics that are tethered through a covalent linker to give a bivalent species. Bivalent diazo bicyclic Smac mimetics function as inhibitors of Inhibitor of Apoptosis Proteins (IAPs). The invention also relates to the use of bivalent diazo bicyclic Smac mimetics for inducing or sensitizing cells to the induction of apoptotic cell death. Thus, compounds of the invention are useful in the treatment, amelioration, or prevention of hyperproliferative diseases such as cancer.

Abstract translation: 本发明涉及通过共价接头连接以产生二价物质的重氮二环Smac模拟物。 二价重氮双环Smac模拟物作为细胞凋亡蛋白抑制剂（IAP）的抑制剂起作用。 本发明还涉及二价重氮二环Smac模拟物用于诱导或致敏细胞诱导凋亡细胞死亡的用途。 因此，本发明的化合物可用于治疗，改善或预防过度增殖性疾病如癌症。

公开(公告)号：US20110184033A1

公开(公告)日：2011-07-28

申请号：US13060306

申请日：2009-08-27

Applicant: Shaomeng Wang ,  Jianyong Chen ,  Gregory Collins ,  James H. Woods ,  Beth Levant

Inventor： Shaomeng Wang ,  Jianyong Chen ,  Gregory Collins ,  James H. Woods ,  Beth Levant

IPC: A61K31/427 ,  C07D277/82 ,  A61P25/28 ,  A61P25/08 ,  A61P25/30 ,  A61P25/22

CPC classification number: C07D277/82 ,  C07D417/12

Abstract: Potent and selective ligands for the dopamine 3 (D3) receptor are disclosed. The D3 receptor ligands have a structural formula (I) wherein X is C═O or SO2, R1 is C1-6 alkyl, R2 is aryl, heteroaryl, aryl, —(CH2)1-3aryl, or —(CH2)1-3heteroaryl, and n is 0 or 1. Methods of using the D3 receptor ligands in the treatment of diseases and conditions wherein modulation of the D3 receptor provides a benefit also are disclosed.

Abstract translation: 公开了多巴胺3（D3）受体的有效和选择性配体。 D3受体配体具有结构式（I），其中X为C = O或SO 2，R 1为C 1-6烷基，R 2为芳基，杂芳基，芳基， - （CH 2）1-3芳基或 - （CH 2） 3杂芳基，n为0或1.D3受体配体在治疗其中D3受体的调节提供益处的疾病和病症方面也被公开。

公开(公告)号：US07932382B2

公开(公告)日：2011-04-26

申请号：US10586271

申请日：2005-01-18

Applicant: Shaomeng Wang ,  Haiying Sun ,  Zaneta Nikolovska-Coleska ,  Chao-Yie Yang ,  Liang Xu

Inventor： Shaomeng Wang ,  Haiying Sun ,  Zaneta Nikolovska-Coleska ,  Chao-Yie Yang ,  Liang Xu

IPC: C07D487/00

CPC classification number: C07K5/0806 ,  C07D487/04 ,  C07K5/0808 ,  C07K5/0827

Abstract: The invention relates to conformationally constrained mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Abstract translation: 本发明涉及Smac的构象约束模拟物，其作为细胞凋亡蛋白抑制剂的抑制剂。 本发明还涉及这些模拟物用于诱导凋亡性细胞死亡和使细胞对细胞凋亡诱导剂敏感的用途。

公开(公告)号：US20100273799A1

公开(公告)日：2010-10-28

申请号：US12822829

申请日：2010-06-24

Applicant: Shaomeng Wang ,  Ke Ding ,  Yipin Lu ,  Zaneta Nikolovska-Coleska ,  Su Qiu ,  Guoping Wang ,  Dongguang Qin ,  Sanjeev Kumar

Inventor： Shaomeng Wang ,  Ke Ding ,  Yipin Lu ,  Zaneta Nikolovska-Coleska ,  Su Qiu ,  Guoping Wang ,  Dongguang Qin ,  Sanjeev Kumar

IPC: A61K31/5377 ,  A61K31/407 ,  A61P35/00 ,  C07D487/10 ,  C07D401/14 ,  A61K31/496 ,  C07D413/14 ,  C12N5/02

CPC classification number: C07D209/54 ,  C07D487/10 ,  C07D491/10

Abstract: The invention relates to small molecules which function as inhibitors of the interaction between p53 and MDM2. The invention also relates to the use of these compounds for inhibiting cell growth, inducing cell death, inducing cell cycle arrest and/or sensitizing cells to additional agent(s).

Abstract translation: 本发明涉及作为p53和MDM2相互作用抑制剂的小分子。 本发明还涉及这些化合物用于抑制细胞生长，诱导细胞死亡，诱导细胞周期停滞和/或使细胞对附加试剂敏感的用途。

公开(公告)号：US20090123480A1

公开(公告)日：2009-05-14

申请号：US12270374

申请日：2008-11-13

Applicant: Shaomeng Wang ,  Haiying Sun ,  Dongguang Qin ,  Zaneta Nikolovska-Coleska ,  Jianfeng Lu ,  Su Qiu ,  Yuefeng Peng ,  Qian Cai

Inventor： Shaomeng Wang ,  Haiying Sun ,  Dongguang Qin ,  Zaneta Nikolovska-Coleska ,  Jianfeng Lu ,  Su Qiu ,  Yuefeng Peng ,  Qian Cai

IPC: A61K31/403 ,  C07D403/04 ,  A61K31/4192 ,  A61K38/19 ,  A61K39/395 ,  A61P35/00

CPC classification number: A61K38/191 ,  C07D487/04 ,  C07D519/00

Abstract: The invention relates to bivalent mimetics of Smac which function as inhibitors of Inhibitor of Apoptosis Proteins. The invention also relates to the use of these mimetics for inducing apoptotic cell death and for sensitizing cells to inducers of apoptosis.

Abstract translation: 本发明涉及Smac的二价模拟物，其作为细胞凋亡蛋白抑制剂的抑制剂。 本发明还涉及这些模拟物用于诱导凋亡性细胞死亡和使细胞对细胞凋亡诱导剂敏感的用途。

公开(公告)号：US20090082445A1

公开(公告)日：2009-03-26

申请号：US12242419

申请日：2008-09-30

Applicant: Shaomeng Wang ,  Jianyong Chen

Inventor： Shaomeng Wang ,  Jianyong Chen

IPC: A61K31/19 ,  A61P35/00

CPC classification number: A61K31/11

Abstract: This invention relates to compositions comprising co-crystals of (−)-gossypol with a C1-8 carboxylic acid or C1-8 sulfonic acid which are useful as inhibitors of Bcl-2 family proteins. The invention also relates to the use of co-crystals of (−)-gossypol with a C1-8 carboxylic acid or C1-8 sulfonic acid for inducing apoptosis in cells and for sensitizing cells to the induction of apoptotic cell death.

Abstract translation: 本发明涉及包含（ - ） - 棉酚与C 1-8羧酸或C 1-8磺酸的共晶体的组合物，其可用作Bcl-2家族蛋白质的抑制剂。 本发明还涉及（ - ） - 棉酚与C 1-8羧酸或C 1-8磺酸的共晶体在细胞中诱导细胞凋亡和促使细胞诱导凋亡细胞死亡的用途。