公开(公告)号：US07388098B2

公开(公告)日：2008-06-17

申请号：US09961932

申请日：2001-09-24

Applicant: John J. Venit ,  Gary D. Madding ,  Victor W. Rosso ,  Francis J. Okuniewicz ,  Robert P. Discordia ,  Susanne Kiau ,  Atul S. Kotnis ,  Michael E. Randazzo ,  D. David Hennings ,  Jingyang Zhu ,  Jason G. Chen

Inventor： John J. Venit ,  Gary D. Madding ,  Victor W. Rosso ,  Francis J. Okuniewicz ,  Robert P. Discordia ,  Susanne Kiau ,  Atul S. Kotnis ,  Michael E. Randazzo ,  D. David Hennings ,  Jingyang Zhu ,  Jason G. Chen

IPC: C07C53/134 ,  C07D233/00 ,  C07D277/00 ,  C07B55/00

CPC classification number: C07D233/78 ,  C07C51/412 ,  C07C51/43 ,  C07C213/08 ,  C07C213/10 ,  C07D233/74 ,  C07C57/58

Abstract: Provided is a dynamic resolution method of enriching a desired isomer of an alpha-substituted carboxylic acid relative to an undesired isomer, the method comprising: (a) in a solvent, contacting the alpha-substituted carboxylic acid, wherein the alpha substitution is with a leaving group and wherein the alpha carbon is chiral, with a homochiral amine to form a salt that is partially insoluble under selected reaction conditions, wherein the homochiral amine is selected so that the solubility of the amine salt of the undesired alpha-substituted carboxylic acid is greater than that of the amine salt of the desired alpha-substituted carboxylic acid under the selected reaction conditions; (b) reacting under the selected reaction conditions the salt with a nucleophile, wherein the reacting is effective in producing a net increase in the less soluble amine salt of the alpha-substituted carboxylic acid, and wherein the selected conditions are selected to (i) promote nucleophilic substitution of the nucleophile and the leaving group or (ii) to produce the increase in the less soluble amine salt in the absence of a strong base; and (c) maintaining the reaction for a period of time effective to increase the amount of the desired alpha-substituted carboxylic acid isomer.

Abstract translation: 提供了相对于不期望的异构体富集α-取代的羧酸的所需异构体的动态拆分方法，该方法包括：（a）在溶剂中使α-取代的羧酸接触，其中α取代为 离去基团，其中所述α碳是手性的，与同基因胺形成在所选择的反应条件下部分不溶的盐，其中选择所述同基因胺，使得不需要的α-取代羧酸的胺盐的溶解度为 在选择的反应条件下大于所需α-取代羧酸的胺盐的浓度; （b）在所选择的反应条件下使所述盐与亲核试剂反应，其中所述反应有效地产生所述α-取代羧酸的较不溶性胺盐的净增加，并且其中所选择的条件选择为：（i） 促进亲核试剂和离去基团的亲核取代，或（ii）在没有强碱的情况下产生较不溶性胺盐的增加; 和（c）保持反应一段时间有效以增加所需的α-取代的羧酸异构体的量。

公开(公告)号：US06968037B2

公开(公告)日：2005-11-22

申请号：US10410910

申请日：2003-04-10

Applicant: Victor W. Rosso ,  Glen Young ,  Joseph Nolfo ,  Imre M. Vit z ,  John J. Venit

Inventor： Victor W. Rosso ,  Glen Young ,  Joseph Nolfo ,  Imre M. Vit z ,  John J. Venit

IPC: B01L3/00 ,  G01N1/28 ,  G01N23/20

CPC classification number: G01N1/4077 ,  B01L3/50255 ,  B01L2200/026 ,  B01L2300/0829 ,  B01L2400/049 ,  G01N23/20 ,  G01N23/20025

Abstract: Multiple samples are prepared in slurry form and deposited through a funnel plate by a multiprobe liquid handler into an array of inserts situated in openings in a housing. Each insert has a recess that extends through the insert body and a filter disc situated in the recess to support the sample. The filter is held in place by an annular part which defines a channel providing access to the filter through the lower portion of the recess. A pressure differential is created across each of the filters by attaching a vacuum manifold to the bottom of the housing to simultaneously remove the liquid from each of the samples, leaving the samples in powder form. The housing is then placed in the X-ray diffractometer for sequential analysis of each of the samples, while the samples are situated in the inserts.

Abstract translation: 多个样品以浆料形式制备并通过漏斗板通过多孔液体处理器沉积到位于壳体中的开口中的插入物阵列中。 每个插入件具有延伸穿过插入体的凹部和位于凹部中以支撑样品的过滤盘。 过滤器通过环形部分保持在适当位置，该环形部分限定了通过凹部的下部进入过滤器的通道。 通过将真空歧管连接到壳体的底部，同时从每个样品中移除液体，使样品成粉末形式，在每个过滤器上形成压差。 然后将壳体放置在X射线衍射仪中，以顺序分析每个样品，而样品位于插入物中。

公开(公告)号：US06184395B2

公开(公告)日：2001-02-06

申请号：US09571234

申请日：2000-05-16

Applicant: Ambarish K. Singh ,  Raymond E. Weaver ,  Gerald L. Powers ,  Victor W. Rosso

Inventor： Ambarish K. Singh ,  Raymond E. Weaver ,  Gerald L. Powers ,  Victor W. Rosso

IPC: C07D30514

CPC classification number: C07D305/14

Abstract: Novel reaction conditions for the cleavage of silyl ethers from silyl protected taxane precursors to afford paclitaxel and paclitaxel analogues in high yield and quality are described. Paclitaxel is prepared from a taxane precursor by treating the taxane precursor with a strong acid such as trifluoroacetic acid in a solvent such as aqueous acetic acid, such that the amount and number of side reactions and taxane impurities are significantly minimized. Also desribed are the crystallization methods for the isolation of paclitaxel in either of the two crystal forms A or B. Paclitaxel and paclitaxel analogues are anti-cancer agents.

Abstract translation: 描述了从甲硅烷基保护的紫杉烷前体裂解甲硅烷基醚以高产率和高质量得到紫杉醇和紫杉醇类似物的新型反应条件。 通过在溶剂如乙酸水溶液中用强酸例如三氟乙酸处理紫杉烷前体，从紫杉烷前体制备紫杉醇，使得副反应的量和数量和紫杉烷杂质显着减少。 还描述了在两种晶型A或B中的任一种中分离紫杉醇的结晶方法。紫杉醇和紫杉醇类似物是抗癌剂。

公开(公告)号：US20130039989A1

公开(公告)日：2013-02-14

申请号：US13643561

申请日：2011-04-29

Applicant: Dilbir S. Bindra ,  Yeshwant Gokhale ,  Cletus John Nunes ,  Victor W. Rosso ,  Gretchen M. Schroeder ,  Ajit B. Thakur ,  Xiaotian Yin

Inventor： Dilbir S. Bindra ,  Yeshwant Gokhale ,  Cletus John Nunes ,  Victor W. Rosso ,  Gretchen M. Schroeder ,  Ajit B. Thakur ,  Xiaotian Yin

IPC: A61K31/444 ,  A61P35/00 ,  C07D401/12 ,  A61K9/14

CPC classification number: C07D401/12 ,  C07D213/82

Abstract: Disclosed are salts and crystalline forms of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide and salts thereof. Also disclosed are at least one pharmaceutical composition comprising at least one crystalline form of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, at least one method of using at least one crystalline form of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide to treat cancer and/or other proliferative diseases, and processes to prepare crystalline forms of N-(4-(2-amino-3-chloropyridin-4-yloxy)-3-fluorophenyl)-4-ethoxy-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide and salts thereof.

公开(公告)号：US20080275009A1

公开(公告)日：2008-11-06

申请号：US12168366

申请日：2008-07-07

Applicant: Ramakrishnan Chidambaram ,  George M. Derbin ,  Masaki Endo ,  Julia ZH Gao ,  Tu Lee ,  Rajeshwar Motheram ,  William Lawrence Parker ,  Victor W. Rosso ,  Sailesh A. Varia

Inventor： Ramakrishnan Chidambaram ,  George M. Derbin ,  Masaki Endo ,  Julia ZH Gao ,  Tu Lee ,  Rajeshwar Motheram ,  William Lawrence Parker ,  Victor W. Rosso ,  Sailesh A. Varia

IPC: A61K31/60 ,  A61K31/506 ,  A61P35/00 ,  C07D403/14

CPC classification number: C07D417/12 ,  A61K31/506 ,  A61K45/06 ,  A61K2300/00

Abstract: Disclosed are a method of treating cancer and/or other proliferative diseases comprising orally administering N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide or a salt thereof, and pharmaceutical compositions comprising N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide or a salt thereof. Also disclosed are N-(2-chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)-1-piperazinyl)-2-methyl-4-pyrimidinyl)amino)-1,3-thiazole-5-carboxamide salts, as well as crystalline forms thereof.

Abstract translation: 公开了一种治疗癌症和/或其它增殖性疾病的方法，其包括口服给予N-（2-氯-6-甲基苯基）-2 - （（6-（4-（2-羟乙基）-1-哌嗪基）-2- 甲基-4-嘧啶基）氨基）-1,3-噻唑-5-甲酰胺或其盐，以及包含N-（2-氯-6-甲基苯基）-2 - （（6-（4-（2 - 羟基乙基）-1-哌嗪基）-2-甲基-4-嘧啶基）氨基）-1,3-噻唑-5-甲酰胺或其盐。 还公开了N-（2-氯-6-甲基苯基）-2 - （（6-（4-（2-羟乙基）-1-哌嗪基）-2-甲基-4-嘧啶基）氨基） 噻唑-5-甲酰胺盐，以及其结晶形式。

公开(公告)号：US08815894B2

公开(公告)日：2014-08-26

申请号：US12777840

申请日：2010-05-11

Applicant: Chenkou Wei ,  Victor W. Rosso ,  Qi Gao

Inventor： Chenkou Wei ,  Victor W. Rosso ,  Qi Gao

IPC: C07D471/04 ,  A61K31/495

CPC classification number: A61K31/4725 ,  A61K31/437 ,  A61K31/438 ,  A61K31/495 ,  A61K45/06 ,  C07D471/04

Abstract: Novel [1,2,4]triazolo[1,5-a]pyridinyl-6-yl-substituted tetrahydroisoquinolines are described in the present invention. These compounds and crystalline forms SA1 and N-2 are used in the treatment of various neurological and physiological disorders. Methods of making these compounds and crystalline forms SA-1 and N-2 are also described in the present invention.

Abstract translation: 在本发明中描述了新的[1,2,4]三唑并[1,5-a]吡啶基-6-基取代的四氢异喹啉。 这些化合物和结晶形式SA1和N-2用于治疗各种神经和生理疾病。 制备这些化合物和结晶形式SA-1和N-2的方法也在本发明中描述。

公开(公告)号：US09556133B2

公开(公告)日：2017-01-31

申请号：US13992022

申请日：2011-12-07

Applicant: Jason Edward Brittain ,  Thomas Jon Seiders ,  Christopher David King ,  Victor W. Rosso

Inventor： Jason Edward Brittain ,  Thomas Jon Seiders ,  Christopher David King ,  Victor W. Rosso

IPC: C07D261/14

CPC classification number: C07D261/14 ,  C07B2200/13

Abstract: Described herein is the LPA1 antagonist 1-{4′-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid (Compound 1), or pharmaceutically acceptable salts thereof. Also described are methods of preparing the LPA1 antagonist, or pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions suitable for administration to a mammal that include the LPA1 antagonist, or pharmaceutically acceptable salt thereof, and methods of using such pharmaceutical compositions for treating LPA-dependent or LPA-mediated diseases or conditions.

Abstract translation: 本文描述的是LPA1拮抗剂1- {4' - [3-甲基-4 - （（R）-1-苯基 - 乙氧基羰基氨基） - 异恶唑-5-基] - 联苯-4-基} - 环丙烷羧酸（化合物1 ）或其药学上可接受的盐。 还描述了制备LPA1拮抗剂或其药学上可接受的盐的方法，以及适用于给予包括LPA1拮抗剂的哺乳动物或其药学上可接受的盐的药物组合物，以及使用该药物组合物治疗LPA- 依赖或LPA介导的疾病或病症。

公开(公告)号：US20130253023A1

公开(公告)日：2013-09-26

申请号：US13992022

申请日：2011-12-07

Applicant: Jason Edward Brittain ,  Thomas Jon Seiders ,  Christopher David King ,  Victor W. Rosso

Inventor： Jason Edward Brittain ,  Thomas Jon Seiders ,  Christopher David King ,  Victor W. Rosso

IPC: C07D261/14

CPC classification number: C07D261/14 ,  C07B2200/13

Abstract: Described herein is the LPA1 antagonist 1-{4′-[3-methyl-4-((R)-1-phenyl-ethoxycarbonylamino)-isoxazol-5-yl]-bi-phenyl-4-yl}-cyclopropanecarboxylic acid (Compound 1), or pharmaceutically acceptable salts thereof. Also described are methods of preparing the LPA1 antagonist, or pharmaceutically acceptable salts thereof, as well as pharmaceutical compositions suitable for administration to a mammal that include the LPA1 antagonist, or pharmaceutically acceptable salt thereof, and methods of using such pharmaceutical compositions for treating LPA-dependent or LPA-mediated diseases or conditions.

Abstract translation: 本文描述的是LPA1拮抗剂1- {4' - [3-甲基-4 - （（R）-1-苯基 - 乙氧基羰基氨基） - 异恶唑-5-基] - 邻 - 苯基-4-基} - 环丙烷羧酸 化合物1）或其药学上可接受的盐。 还描述了制备LPA1拮抗剂或其药学上可接受的盐的方法，以及适用于给予包括LPA1拮抗剂的哺乳动物或其药学上可接受的盐的药物组合物，以及使用该药物组合物治疗LPA- 依赖或LPA介导的疾病或病症。

公开(公告)号：US20110086857A1

公开(公告)日：2011-04-14

申请号：US12901614

申请日：2010-10-11

Applicant: Percy H. Carter ,  Robert J. Cherney ,  Victor W. Rosso ,  Jun Li

Inventor： Percy H. Carter ,  Robert J. Cherney ,  Victor W. Rosso ,  Jun Li

IPC: A61K31/53 ,  C07D487/04 ,  A61P35/00 ,  A61P3/04 ,  A61P3/10 ,  A61P3/00 ,  A61P25/00 ,  A61P25/04 ,  A61P9/10 ,  A61P9/12 ,  A61P17/06 ,  A61P17/00 ,  A61P19/02 ,  A61P9/04 ,  A61P9/00 ,  A61P29/00 ,  A61P31/18 ,  A61P1/00 ,  A61P13/12 ,  A61P25/28

CPC classification number: A61K31/53 ,  C07D487/04

Abstract: The present invention provides a novel antagonist: N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide: or a pharmaceutically acceptable salt, solvate or prodrug, thereof, having unexpected dual CCR-2 and CCR-5 receptor activity. Crystalline forms, metabolites, pharmaceutical compositions containing the same and methods of using the same as agents for the treatment of inflammatory diseases, allergic, autoimmune, metabolic, cancer and/or cardiovascular diseases are also disclosed. The present disclosure also provides processes for preparing compounds of Formula (I) as provided herein, including N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-a][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide. Compounds that are useful intermediates of the process are also provided herein.

Abstract translation: 本发明提供新的拮抗剂：N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S）-3-（7-叔丁基吡唑并[1,5-a] 1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺：或其药学上可接受的盐，溶剂合物或前药，具有意想不到的双重CCR-2和CCR-5受体活性。 还公开了结晶形式，代谢物，含有其的药物组合物和使用其作为治疗炎性疾病，过敏性，自身免疫性，代谢性，癌症和/或心血管疾病的药剂的方法。 本公开还提供了制备本文提供的式（I）化合物的方法，包括N - （（1R，2S，5R）-5-（叔丁基氨基）-2 - （（S） 叔丁基吡唑并[1,5-a] [1,3,5]三嗪-4-基氨基）-2-氧代吡咯烷-1-基）环己基）乙酰胺。 本文还提供了该方法有用中间体的化合物。

公开(公告)号：US20100292250A1

公开(公告)日：2010-11-18

申请号：US12777840

申请日：2010-05-11

Applicant: CHENKOU WEI ,  VICTOR W. ROSSO ,  QI GAO

Inventor： CHENKOU WEI ,  VICTOR W. ROSSO ,  QI GAO

IPC: A61K31/495 ,  C07D471/04 ,  A61K31/437 ,  A61K31/438 ,  A61P25/16 ,  A61P25/28 ,  A61P3/04 ,  A61P3/10

CPC classification number: A61K31/4725 ,  A61K31/437 ,  A61K31/438 ,  A61K31/495 ,  A61K45/06 ,  C07D471/04

Abstract: Novel [1,2,4]triazolo[1,5-a]pyridinyl-6-yl-substituted tetrahydroisoquinolines are described in the present invention. These compounds and crystalline forms SA1 and N-2 are used in the treatment of various neurological and physiological disorders. Methods of making these compounds and crystalline forms SA-1 and N-2 are also described in the present invention.

Abstract translation: 在本发明中描述了新的[1,2,4]三唑并[1,5-a]吡啶基-6-基取代的四氢异喹啉。 这些化合物和结晶形式SA1和N-2用于治疗各种神经和生理疾病。 制备这些化合物和结晶形式SA-1和N-2的方法也在本发明中描述。