公开(公告)号：US08236984B2

公开(公告)日：2012-08-07

申请号：US12728361

申请日：2010-03-22

Applicant: Mark Brian Pepys ,  Steven Victor Ley ,  Angus John Morrison ,  Vittorio Bellotti ,  Simon Kolstoe ,  Martin Smith

Inventor： Mark Brian Pepys ,  Steven Victor Ley ,  Angus John Morrison ,  Vittorio Bellotti ,  Simon Kolstoe ,  Martin Smith

IPC: C07C63/33 ,  A01N37/30

CPC classification number: A61K31/194

Abstract: The present invention relates to compounds of formula (I) for stabilizing the tetrameric form of transthyretin, compounds for use in the treatment or prevention of amyloidosis, and agents and medicaments comprising such compounds. wherein X, Y, R1, R2, R3, R4, m, n, p, q, and the linker are as defined herein.

Abstract translation: 本发明涉及用于稳定转甲状腺素蛋白的四聚体形式的式（I）化合物，用于治疗或预防淀粉样变性的化合物，以及包含这些化合物的药剂和药物。 其中X，Y，R 1，R 2，R 3，R 4，m，n，p，q和连接体如本文所定义。

公开(公告)号：US08026280B2

公开(公告)日：2011-09-27

申请号：US10025947

申请日：2001-12-26

Applicant: Hsuan-Yin Lan-Hargest ,  Robert J. Kaufman ,  Norbert L Wiech

Inventor： Hsuan-Yin Lan-Hargest ,  Robert J. Kaufman ,  Norbert L Wiech

IPC: A61K31/20 ,  A61K31/195 ,  A61K31/19 ,  C07C63/33 ,  C07C63/64

CPC classification number: A61K31/16 ,  C07C57/42 ,  C07C57/60 ,  C07C259/06 ,  C07D307/54

Abstract: Histone deacetylase is a metallo-enzyme with zinc at the active site. Compounds having a zinc-binding moiety, such as, for example, a carboxylic acid group, can inhibit histone deacetylase. Histone deacetylase inhibition can repress gene expression, including expression of genes related to tumor suppression. Accordingly, inhibition of histone deacetylase can provide an alternate route for treating cancer, hematological disorders, e.g., hemoglobinopathies, and genetic related metabolic disorders, e.g., cystic fibrosis and adrenoleukodystrophy. Carboxylic acid-containing compounds having a terminal cyclic moiety, a carboxylic acid group, and a C3-12 hydrocarbon chain optionally containing at least one double bond, at least one triple bond, or at least one double bond and one triple bond linking the cyclic moiety and the carboxylic acid group are inhibitors of histone deacetylase.

Abstract translation: 组蛋白脱乙酰酶是在活性位点具有锌的金属酶。 具有锌结合部分（例如羧酸基团）的化合物可抑制组蛋白脱乙酰酶。 组蛋白脱乙酰酶抑制可抑制基因表达，包括与肿瘤抑制相关的基因的表达。 因此，组蛋白脱乙酰酶的抑制可以提供用于治疗癌症，血液学疾病，例如血红蛋白病和遗传相关代谢紊乱（例如囊性纤维化和肾上腺脑白质营养不良）的替代途径。 含有末端环状部分的羧酸化合物，羧酸基团和任选含有至少一个双键的C3-12烃链，至少一个三键，或至少一个双键和一个三键，连接环状 部分和羧酸基团是组蛋白脱乙酰酶的抑制剂。

公开(公告)号：US20110144207A1

公开(公告)日：2011-06-16

申请号：US13058978

申请日：2009-08-14

Applicant: Nandkumar Chodankar ,  Milind Biyani ,  Mohan Muthunarayanan ,  Selvaraju Radhakrishnan ,  Sathish Kumar Santhanampillai ,  Rajendran Paul Nadar ,  Vivekanandan Sundaramurthy ,  Sakthivel Lakshamana Prabu

Inventor： Nandkumar Chodankar ,  Milind Biyani ,  Mohan Muthunarayanan ,  Selvaraju Radhakrishnan ,  Sathish Kumar Santhanampillai ,  Rajendran Paul Nadar ,  Vivekanandan Sundaramurthy ,  Sakthivel Lakshamana Prabu

IPC: A61K31/19 ,  C07C63/00 ,  C07C63/04 ,  C07C65/24 ,  C07C229/40 ,  C07D209/26 ,  C07D491/052 ,  C07C63/33 ,  C07C59/185 ,  A61P29/00

CPC classification number: A61K9/2018 ,  A61K9/2054 ,  A61K9/2059 ,  C07C51/412 ,  C07C57/30 ,  C07C59/56 ,  C07C59/64 ,  C07C227/16 ,  C07D209/28 ,  C07C229/42

Abstract: The invention particularly discloses a process for preparing aryl alkyl carboxylic acid salts by preparing aqueous alkali solution, adding aryl alkyl carboxylic acid to said alkali solution at a temperature ranging from 4° to 121° C. for obtaining a clear solution, preferably by heating and/or stirring and concentrating and cooling to obtain aryl alkyl carboxylic acid salt The invention therefore discloses solid oral dosage forms and compositions of aryl alkyl carboxylic acid salts which are free of organic solvent/so. The solid oral dose compositions of aryl alkyl carboxylic acid salts of the invention are prepared in situ from aryl alkyl carboxylic acids and bases to obtain aryl acid alkyl carboxylic acid sails in crystalline/powder form with or without the use of pharmaceutical excipients.

Abstract translation: 本发明特别公开了一种制备芳基烷基羧酸盐的方法，通过制备碱水溶液，在4℃至121℃的温度范围内向所述碱溶液中加入芳基烷基羧酸，以获得澄清溶液，优选通过加热和 /或搅拌并浓缩并冷却以获得芳基烷基羧酸盐因此，本发明公开了不含有机溶剂的固体口服剂型和芳基烷基羧酸盐的组合物。 本发明的芳基烷基羧酸盐的固体口服剂量组合物由芳基烷基羧酸和碱原位制备得到具有或不使用药用赋形剂的结晶/粉末形式的芳基烷基羧酸帆。

公开(公告)号：US07560589B2

公开(公告)日：2009-07-14

申请号：US10565296

申请日：2004-07-27

Applicant: Jonathan E. Britton ,  Jing Fang ,  Dennis Heyer ,  Aaron Bayne Miller ,  Frank Navas, III ,  Terrence Lee Smalley, Jr. ,  William J. Zuercher ,  Subba Reddy Katamreddy

Inventor： Jonathan E. Britton ,  Jing Fang ,  Dennis Heyer ,  Aaron Bayne Miller ,  Frank Navas, III ,  Terrence Lee Smalley, Jr. ,  William J. Zuercher ,  Subba Reddy Katamreddy

IPC: C07C63/33

CPC classification number: C07D207/333 ,  C07C39/23 ,  C07C39/42 ,  C07C43/23 ,  C07C45/45 ,  C07C45/46 ,  C07C45/59 ,  C07C45/62 ,  C07C45/673 ,  C07C45/71 ,  C07C47/57 ,  C07C49/403 ,  C07C49/83 ,  C07C49/835 ,  C07C49/84 ,  C07C59/54 ,  C07C59/56 ,  C07C65/19 ,  C07C233/25 ,  C07C235/34 ,  C07C235/42 ,  C07C255/13 ,  C07C255/53 ,  C07C311/08 ,  C07C311/21 ,  C07C317/22 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/18 ,  C07D207/16 ,  C07D211/60 ,  C07D211/62 ,  C07D213/30 ,  C07D239/26 ,  C07D261/08 ,  C07D263/32 ,  C07D295/096 ,  C07D307/42 ,  C07D309/20 ,  C07D309/22 ,  C07D335/02 ,  C07F9/4015

Abstract: The present invention relates to novel compounds with a variety of therapeutic uses, more particularly novel substituted cyclic alkylidene compounds that are particularly useful for selective estrogen receptor modulation.

Abstract translation: 本发明涉及具有多种治疗用途的新化合物，更特别地涉及特别适用于选择性雌激素受体调节的新型取代的环亚烷基化合物。

公开(公告)号：US20090170948A1

公开(公告)日：2009-07-02

申请号：US12313961

申请日：2008-11-26

Applicant: Valerie Niddam-Hildesheim ,  Eli Lancry ,  Sharona Shachan-tov ,  Sigalit Levi ,  Tamar Nidam

Inventor： Valerie Niddam-Hildesheim ,  Eli Lancry ,  Sharona Shachan-tov ,  Sigalit Levi ,  Tamar Nidam

IPC: A61K31/195 ,  C07C63/33 ,  A61P25/24

CPC classification number: C07C215/64 ,  C07C57/15 ,  C07C2601/14

Abstract: Provided are crystalline forms of O-desmethylvenlafaxine fumarate, methods for their preparation, and pharmaceutical compositions thereof.

Abstract translation: 提供了O-去甲基文拉法辛富马酸盐的结晶形式，其制备方法及其药物组合物。

公开(公告)号：US20090054506A1

公开(公告)日：2009-02-26

申请号：US11887125

申请日：2006-03-24

Applicant: Rui Liang ,  Emma R. Parmee

Inventor： Rui Liang ,  Emma R. Parmee

IPC: A61K31/41 ,  C07D257/06 ,  C07C61/12 ,  A61K31/195 ,  A61K31/352 ,  A61P3/10 ,  A61K31/192 ,  C07C63/33 ,  C07D311/04

CPC classification number: C07C323/44 ,  C07C237/48 ,  C07C275/30 ,  C07C275/34 ,  C07C2601/14 ,  C07C2602/08 ,  C07C2602/10 ,  C07D257/06 ,  C07D311/68 ,  C07D317/60 ,  C07D319/08 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12

Abstract: Substituted aryl and heteroaryl derivatives are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.

Abstract translation: 公开了取代的芳基和杂芳基衍生物。 该化合物可用于治疗2型糖尿病及相关病症。 还包括药物组合物和治疗方法。

公开(公告)号：US20090036536A1

公开(公告)日：2009-02-05

申请号：US12213178

申请日：2008-06-16

Applicant: Thibaud Biadatti ,  Etienne Thoreau

Inventor： Thibaud Biadatti ,  Etienne Thoreau

IPC: A61K31/192 ,  C07C63/33 ,  A61P17/06 ,  A61P17/10

CPC classification number: C07C65/17 ,  C07C51/09 ,  C07C67/31 ,  C07C67/343 ,  C07C2602/10 ,  C07C69/76 ,  C07C69/94

Abstract: Biphenyl compounds having the formula (I): are useful for preventing/treating pathologies linked to a deficiency of the activation of the RAR gamma receptor, e.g., for treating a pathology linked to a cell differentiation and/or proliferation disorder, for treating acne, for treating psoriasis.

Abstract translation: 具有式（I）的联苯化合物可用于预防/治疗与RARγ受体活化缺陷相关的病症，例如用于治疗与细胞分化和/或增殖病症相关的病理学，用于治疗痤疮， 用于治疗牛皮癣。

公开(公告)号：US07385083B2

公开(公告)日：2008-06-10

申请号：US10664165

申请日：2003-09-17

Applicant: Yuji Imaizumi ,  Tomohiko Ohwada

Inventor： Yuji Imaizumi ,  Tomohiko Ohwada

IPC: C07C65/01 ,  C07C63/33 ,  C07C62/12 ,  C07C62/14 ,  C07C62/22

CPC classification number: A61K31/19

Abstract: A potassium channel opener comprising a compound (e.g., pimaric acid) represented by the formula [I]: wherein R1, R2, R3, R4, R5, R6 and R7 are each independently hydrogen, alkyl, alkenyl, halogen, hydroxy, halogenated alkyl, hydroxyalkyl, aminoalkyl, alkoxy, aryl, heteroaryl, acyl, carboxyl, alkoxycarbonyl, hydroxamate, sulfo, carbamoyl, sulfonamide, aldehyde, or nitrile; or R4 and R5 may be bonded to each other to form a ring; or R6 and R7 may be bonded to each other to form a ring; and all of three bonds represented by are single bonds, or one of the three bonds is double bond and the other bonds are single bonds, or a physiologically acceptable salt thereof as an effective ingredient.

Abstract translation: 钾通道开放剂，其包含由式[I]表示的化合物（例如，海松酸）：其中R 1，R 2，R 3， >，R 4，R 5，R 6和R 7各自独立地为氢，烷基，烯基， 卤素，羟基，卤代烷基，羟基烷基，氨基烷基，烷氧基，芳基，杂芳基，酰基，羧基，烷氧基羰基，异羟肟酸酯，磺基，氨基甲酰基，磺酰胺，醛或腈; 或R 4和R 5可以彼此键合形成环; 或R 6和R 7可以彼此键合形成环; 并且由是单键，或三键之一是双键，另一个键是单键，或其生理学上可接受的盐作为有效成分。

公开(公告)号：US06864390B2

公开(公告)日：2005-03-08

申请号：US10149160

申请日：2000-11-30

Applicant: Justin Stephen Bryans ,  David Clive Blakemore ,  Sophie Caroline Williams

Inventor： Justin Stephen Bryans ,  David Clive Blakemore ,  Sophie Caroline Williams

IPC: C07C51/08 ,  C07C51/41 ,  C07C51/43 ,  C07C69/608 ,  C07C69/616 ,  C07C227/32 ,  C07C229/28 ,  C07C255/31 ,  C07C255/41 ,  C07C265/08 ,  C07C271/12 ,  C07C63/33 ,  C07C61/16 ,  C07C61/20

CPC classification number: C07C271/12 ,  C07B2200/07 ,  C07C51/08 ,  C07C51/412 ,  C07C51/43 ,  C07C69/608 ,  C07C69/616 ,  C07C227/32 ,  C07C229/28 ,  C07C255/31 ,  C07C255/41 ,  C07C265/08 ,  C07C2601/08 ,  C07C57/46

Abstract: The instant invention is a route to stereospecific 3-substituted 5-membered ring isomers of Formula (A). The final products are useful as agents in the treatment of epilepsy, faintness attacks, hypokinesia, cranial disorders, neurodegenerative disorders, depression, anxiety, panic, pain, neuropathological disorders, gastrointestinal disorders such as irritable bowel syndrome (IBS), inflammation especially arthritis, sleep disorders, premenstrual syndrome, and hot flashes. The invention provides novel routes to synthesize steroselectively analogs of gabapentin (Neurontin®) of Formulas (I), (II), (III) and (IV) wherein R is C1-C10 alkyl or C3-C10 cycloalkyl and pharmaceutically acceptable salts thereof.

Abstract translation: 本发明是式（A）的立体特异性3-取代的五元环异构体的途径。 最终产品可用作治疗癫痫，微弱发作，运动不良，颅内疾病，神经退行性疾病，抑郁症，焦虑症，恐慌症，疼痛，神经病理学障碍，胃肠道疾病如肠易激综合征（IBS），炎症，尤其是关节炎， 睡眠障碍，经前期综合征和潮热。 本发明提供了合成式（I），（II），（III）和（IV）的加巴喷丁（Neurontin）的甾体类似物的新途径，其中R是C 1 -C 10烷基或C 3 -C 10环烷基和药学上可接受的盐 其中。

公开(公告)号：US5877207A

公开(公告)日：1999-03-02

申请号：US880823

申请日：1997-06-24

Applicant: Elliott S. Klein ,  Alan T. Johnson ,  Andrew M. Standeven ,  Richard L. Beard ,  Samuel J. Gillett ,  Tien T. Duong ,  Sunil Nagpal ,  Vidyasagar Vuligonda ,  Min Teng ,  Roshantha A. Chandraratna

Inventor： Elliott S. Klein ,  Alan T. Johnson ,  Andrew M. Standeven ,  Richard L. Beard ,  Samuel J. Gillett ,  Tien T. Duong ,  Sunil Nagpal ,  Vidyasagar Vuligonda ,  Min Teng ,  Roshantha A. Chandraratna

IPC: C07D333/24 ,  A61K31/245 ,  A61K31/353 ,  A61K31/381 ,  A61P3/10 ,  A61P17/16 ,  A61P19/08 ,  A61P39/02 ,  A61P43/00 ,  C07C57/50 ,  C07C63/33 ,  C07C63/49 ,  C07C63/66 ,  C07C63/72 ,  C07C63/74 ,  C07C65/19 ,  C07C65/28 ,  C07C65/38 ,  C07C69/618 ,  C07C69/76 ,  C07C69/90 ,  C07C69/94 ,  C07C233/81 ,  C07C233/87 ,  C07C245/10 ,  C07C327/48 ,  C07D213/55 ,  C07D277/30 ,  C07D307/54 ,  C07D311/58 ,  C07D335/06 ,  C07F7/08 ,  C07F7/18 ,  A61K31/35 ,  C07D311/04

CPC classification number: C07C57/50 ,  C07C233/81 ,  C07C233/87 ,  C07C245/10 ,  C07C327/48 ,  C07C63/33 ,  C07C63/49 ,  C07C63/66 ,  C07C63/72 ,  C07C63/74 ,  C07C65/19 ,  C07C65/28 ,  C07C65/38 ,  C07C69/618 ,  C07C69/76 ,  C07C69/90 ,  C07C69/94 ,  C07D213/55 ,  C07D277/30 ,  C07D307/54 ,  C07D311/58 ,  C07D333/24 ,  C07D335/06 ,  C07F7/0818 ,  C07C2102/10 ,  C07C2102/28

Abstract: Aryl-substituted and aryl and (3-oxo-1-propenly)-substituted benzopyran, benzothiopyran, 1,2-dihydroquinoline, and 5,6-dihydronaphthalene derivatives have retinoid negative hormone and/or antagonist-like biological activities. The invented RAR antagonists can be administered to mammals, including humans, for the purpose of preventing or diminishing action of RAR agonists on the bound receptor sites. Specifically, the RAR agonists are administered or coadministered with retinoid drugs to prevent or ameliorate toxicity or side effects caused by retinoids or vitamin A or vitamin A precursors. The retinoid negative hormones can be used to potentiate the activities of other retinoids and nuclear receptor agonists. For example, the retinoid negative hormone called AGN 193109 effectively increased the effectiveness of other retinoids and steroid hormones in in vitro transactivation assays. Additionally, transactivation assays can be used to identify compounds having negative hormone activity. These assays are based on the ability of negative hormones to down-regulate the activity of chimeric retinoid receptors engineered to possess a constitutive transcription activator domain.