1-(tert-butyl) 2-methyl (2S,4R)-4-(piperidin-1-yl)pyrrolidine-1,2-dicarboxylate | 913730-62-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1-(tert-butyl) 2-methyl (2S,4R)-4-(piperidin-1-yl)pyrrolidine-1,2-dicarboxylate
• 英文别名: 1-O-tert-butyl 2-O-methyl (2S,4R)-4-piperidin-1-ylpyrrolidine-1,2-dicarboxylate
• CAS: 913730-62-8
• 化学式: C₁₆H₂₈N₂O₄
• 分子量: 312.409
• InChiKey: AVRPCRVJQBQIKY-OLZOCXBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(tert-butyl) 2-methyl (2S,4R)-4-(piperidin-1-yl)pyrrolidine-1,2-dicarboxylate 在 盐酸 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 反应 18.0h， 以8.2 g的产率得到methyl (2S,4R)-4-(piperidin-1-yl)pyrrolidine-2-carboxylate hydrochloride
  参考文献：
  名称：

  [EN] ALIPHATIC PROLINAMIDE DERIVATIVES
  [FR] DÉRIVÉS DE PROLINAMIDE ALIPHATIQUE

  摘要：

  这项发明涉及一种新型的脂肪族脯氨酰胺衍生物，其化学式为I，并且包括药学上可接受的盐、溶剂化合物、盐的溶剂化合物和其前药，用于预防（例如，延缓或减少发展风险）和治疗（例如，控制、缓解或减缓进展）与眼睛相关的年龄相关性黄斑变性（AMD）及相关眼部疾病。这些疾病包括干性AMD、湿性AMD、地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜血管病变以及视网膜或光感受器细胞的退化。本公开的发明还涉及预防、减缓进展和治疗干性AMD、湿性AMD和地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜血管病变以及视网膜或光感受器细胞的方法，包括：给予所述发明化合物的治疗有效量。本发明的化合物是HTRAl的抑制剂。因此，本发明的化合物在预防和治疗一系列（全部或部分）由HTRAl介导的疾病中具有用途。本发明的化合物还可用于抑制眼部或关节炎或相关疾病部位的HTRAl蛋白酶活性。

  公开号：

  WO2017222917A1
• 作为产物：
  描述：

  哌啶 在 三氟甲磺酸酐 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 1-(tert-butyl) 2-methyl (2S,4R)-4-(piperidin-1-yl)pyrrolidine-1,2-dicarboxylate
  参考文献：
  名称：

  WO2006/115918

  摘要：

  公开号：

文献信息

• [EN] BORONIC ACID DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS D'ACIDE BORONIQUE ET LEURS UTILISATIONS
  申请人：INCEPTION 4 INC

  公开号：WO2016100555A1

  公开（公告）日：2016-06-23

  This invention is directed to novel Boronic acid derivatives of Formula I, and pharmaceutically acceptable salts, solvate, solvate of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of Age-related Macular Degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, Wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor ceils. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry -AMD, Wet- AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRA1. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range diseases mediated (in whole or in part) by HTRA1. The compounds of the invention are also useful for inhibiting HTRA1 protease activity in an eye or locus of an arthritis or related condition.

  这项发明涉及一种新型的化学式I的硼酸衍生物，以及在预防（例如，延缓或减少发展风险）和治疗（例如，控制、缓解或减缓进展）老年性黄斑变性（AMD）及眼部相关疾病中有用的药用盐、溶剂化合物、盐的溶剂化合物和其前体。这些疾病包括干性AMD、湿性AMD、地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜血管病变以及视网膜或光感受细胞的退化。本公开的发明还涉及预防、减缓进展和治疗干性AMD、湿性AMD和地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜血管病变以及视网膜或光感受细胞的方法，包括：给予所述发明化合物的治疗有效量。本发明的化合物是HTRA1的抑制剂。因此，本发明的化合物在预防和治疗一系列（全部或部分）由HTRA1介导的疾病中有用。本发明的化合物还可用于抑制眼部或关节炎或相关疾病部位中的HTRA1蛋白酶活性。
• [EN] CARBOCYCLIC PROLINAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS DE PROLINAMIDE CARBOCYCLIQUES
  申请人：INCEPTION 4 INC

  公开号：WO2017222914A1

  公开（公告）日：2017-12-28

  This invention is directed to novel carbocyclic prolinamide derivatives of Formula (I), and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRA1. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range of diseases mediated (in whole or in part) by HTRA1. The compounds of the invention are also useful for inhibiting HTRA1 protease activity in an eye or locus of an arthritis or related condition.

  这项发明涉及一种新型的Formula (I)的碳环脯氨酰胺衍生物，以及在预防（例如，延缓或降低发展风险）和治疗（例如，控制、缓解或减缓进展）与眼睛相关的年龄相关性黄斑变性（AMD）和相关疾病方面有用的药用盐、溶剂化合物、盐的溶剂化合物和前药。这些疾病包括干性AMD、湿性AMD、地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜脉络膜病变以及视网膜或光感受器细胞的退化。本公开的发明还涉及预防、减缓进展和治疗干性AMD、湿性AMD和地理性萎缩、糖尿病视网膜病变、早产儿视网膜病变、多发性脉络膜脉络膜病变以及视网膜或光感受器细胞的方法，包括：给予所述发明的化合物的治疗有效量。本发明的化合物是HTRA1的抑制剂。因此，本发明的化合物在预防和治疗通过HTRA1（全部或部分）介导的广泛疾病方面有用。本发明的化合物还可用于抑制眼睛或关节炎或相关疾病部位的HTRA1蛋白酶活性。
• VLA-4 Antagonists
  申请人：Liu Ping

  公开号：US20090069376A1

  公开（公告）日：2009-03-12

  Substituted N—[N-(sulphonylphenyl)sulfonyl-prolyl]-phenylalanine derivatives of the present invention are antagonists of the VLA-4 integrin and are useful in the treatment, prevention and suppression of diseases mediated by VLA-4-binding and cell adhesion and activation. Moreover, the compounds of the present invention demonstrate significant receptor occupancy of VLA-4 bearing cells after oral administration and are suitable for once-, twice-, or thrice-a-day oral administration. This invention also relates to compositions containing such compounds and methods of treatment using such compounds.

  本发明的N-[N-(磺酰基苯基)磺酰基-脯氨酸]-苯丙氨酸衍生物是VLA-4整合素的拮抗剂，可用于治疗、预防和抑制通过VLA-4结合和细胞黏附和激活介导的疾病。此外，本发明的化合物在口服后表现出显著的VLA-4受体占有率，并适用于一天一次、两次或三次口服。本发明还涉及含有此类化合物的组合物和使用此类化合物的治疗方法。
• Aliphatic prolinamide derivatives
  申请人：ORION OPHTHALMOLOGY LLC

  公开号：US10730832B2

  公开（公告）日：2020-08-04

  This invention is directed to novel aliphatic prolinamide derivatives of Formula I, and pharmaceutically acceptable salts, solvates, solvates of the salt and prodrugs thereof, useful in the prevention (e.g., delaying the onset of or reducing the risk of developing) and treatment (e.g., controlling, alleviating, or slowing the progression of) of age-related macular degeneration (AMD) and related diseases of the eye. These diseases include dry-AMD, wet-AMD, geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells. The invention disclosed herein is further directed to methods of prevention, slowing the progress of, and treatment of dry-AMD, wet-AMD, and geographic atrophy, diabetic retinopathy, retinopathy of prematurity, polypoidal choroidal vasculopathy, and degeneration of retinal or photoreceptor cells, comprising: administration of a therapeutically effective amount of compound of the invention. The compounds of the invention are inhibitors of HTRA1. Thus, the compounds of the invention are useful in the prevention and treatment of a wide range of diseases mediated (in whole or in part) by HTRA1. The compounds of the invention are also useful for inhibiting HTRA1 protease activity in an eye or locus of an arthritis or related condition.

  本发明涉及式I的新型脂肪族丙氨酰胺衍生物及其药学上可接受的盐、溶液剂、盐的溶解物和原药，可用于预防（如延缓发病或降低发病风险）和治疗（如控制、减轻或延缓进展）老年性黄斑变性（AMD）及相关眼部疾病。这些疾病包括干性黄斑变性、湿性黄斑变性、地理萎缩、糖尿病视网膜病变、早产儿视网膜病变、多形性脉络膜血管病变以及视网膜或感光细胞变性。本文公开的本发明进一步涉及预防、减缓干性-AMD、湿性-AMD 和地理萎缩、糖尿病视网膜病变、早产儿视网膜病变、多形性脉络膜血管病变以及视网膜或感光细胞变性的进展和治疗方法，包括：施用治疗有效量的本发明化合物。本发明化合物是 HTRA1 的抑制剂。因此，本发明化合物可用于预防和治疗由 HTRA1（全部或部分）介导的多种疾病。本发明的化合物还可用于抑制关节炎或相关疾病的眼部或病灶中的 HTRA1 蛋白酶活性。
• Discovery of <i>N</i>-{<i>N</i>-[(3-Cyanophenyl)sulfonyl]-4(<i>R</i>)-cyclobutylamino-(<scp>l</scp>)-prolyl}-4-[(3′,5′-dichloroisonicotinoyl)amino]-(<scp>l</scp>)-phenylalanine (MK-0668), an Extremely Potent and Orally Active Antagonist of Very Late Antigen-4
  作者：Linus S. Lin、Thomas Lanza、James P. Jewell、Ping Liu、Carrie Jones、Gerard R. Kieczykowski、Kelly Treonze、Qian Si、Salony Manior、Gloria Koo、Xinchun Tong、Junying Wang、Anne Schuelke、James Pivnichny、Regina Wang、Conrad Raab、Stella Vincent、Philip Davies、Malcolm MacCoss、Richard A. Mumford、William K. Hagmann

  DOI：10.1021/jm900257b

  日期：2009.6.11

  Extremely potent very late antigen-4 (VLA-4) antagonists with picomolar, whole blood activity and slow dissociation rates were discovered by incorporating an amino substituent on the proline fragment of the initial lead structure. This level of potency against the unactivated form of VLA-4 was shown to be sufficient to overcome the poor pharmacokinetic profiles typical of this class of VLA-4 antagonists, and sustained activity as measured by receptor occupancy was achieved in preclinical species after oral dosing.