(R)-(3-aminopiperidin-1-yl)(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone | 1549810-81-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R)-(3-aminopiperidin-1-yl)(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone
• 英文别名: [(3r)-3-Aminopiperidin-1-Yl][2-(1-Ethyl-1h-Pyrrolo[2,3-B]pyridin-2-Yl)-7-Methoxy-1-Methyl-1h-Benzimidazol-5-Yl]methanone；[(3R)-3-aminopiperidin-1-yl]-[2-(1-ethylpyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methylbenzimidazol-5-yl]methanone
• CAS: 1549810-81-2
• 化学式: C₂₄H₂₈N₆O₂
• 分子量: 432.525
• InChiKey: JCCVZBCVMBEDEN-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  91.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-(3-aminopiperidin-1-yl)(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以2.43 g的产率得到(R)-(3-aminopiperidin-1-yl)(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone hydrochloride
  参考文献：
  名称：

  [EN] 2 - (AZAINDOL- 2 -YL) BENZ IMIDAZOLES AS PAD4 INHIBITORS
  [FR] 2-(AZAINDOL-2-YL)BENZIMIDAZOLES UTILISÉS COMME INHIBITEURS DE PAD4

  摘要：

  式（I）的化合物，其中; R1为氢或C1-6烷基; R2为氢，C1-6烷基，全氟甲基C0-5烷基-O-，或C1-6烷氧基; R3为氢，C1-6烷基，或C1-6烷氧基C1-6烷基; R4为氢，C1-6烷基，全氟甲基C1-6烷基; 或未取代的C3-6环烷基C1-6烷基; A为C-R5或N; B为C-R6或N; D为C-R7或N; 但A、B和D中至少有一个为N; R5为氢或C1-6烷基; R6为氢或C1-6烷基; R7为氢，C1-6烷基，C1-6烷氧基，或羟基; R8为氢或C1-6烷基，但R4和R8中至少有一个为氢; R9为氢或羟基; R10为氢或C1-6烷基; 其盐是PAD4抑制剂，可能对多种疾病的治疗有用，例如类风湿关节炎、血管炎、系统性红斑狼疮、溃疡性结肠炎、癌症、囊性纤维化、哮喘、皮肤性红斑狼疮和银屑病。

  公开号：

  WO2014015905A1
• 作为产物：
  描述：

  4-氯-3-甲氧基-5-硝基苯羧酸甲酯 在 sodium dithionite 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.5h， 生成 (R)-(3-aminopiperidin-1-yl)(2-(1-ethyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-7-methoxy-1-methyl-1H-benzo[d]imidazol-5-yl)methanone
  参考文献：
  名称：

  2-(AZAINDOL-2-YL)BENZIMIDAZOLES AS PAD4 INHIBITORS

  摘要：

  式（I）的化合物：其中；R1为氢或C1-6烷基；R2为氢、C1-6烷基、全氟甲基C0-5烷基-O—、或C1-6烷氧基；R3为氢、C1-6烷基，或C1-6烷氧基C1-6烷基；R4为氢、C1-6烷基、全氟甲基C1-6烷基；或未取代的C3-6环烷基C1-6烷基；A为C—R5或N；B为C—R6或N；D为C—R7或N；但要求A、B、和D中至少有一个为N；R5为氢或C1-6烷基；R6为氢或C1-6烷基；R7为氢、C1-6烷基、C1-6烷氧基，或羟基；R8为氢或C1-6烷基，但要求R4和R8中的一个为氢；R9为氢或羟基；R10为氢或C1-6烷基；其盐为PAD4抑制剂，可能在治疗各种疾病中有用，例如类风湿性关节炎、血管炎、系统性红斑狼疮、溃疡性结肠炎、癌症、囊性纤维化、哮喘、皮肤红斑性狼疮和牛皮癣。

  公开号：

  US20150175600A1

文献信息

• [EN] 2 - (AZAINDOL- 2 -YL) BENZ IMIDAZOLES AS PAD4 INHIBITORS<br/>[FR] 2-(AZAINDOL-2-YL)BENZIMIDAZOLES UTILISÉS COMME INHIBITEURS DE PAD4
  申请人：GLAXO GROUP LTD

  公开号：WO2014015905A1

  公开（公告）日：2014-01-30

  Compounds of formula (I) wherein; R1 is hydrogen or C1-6alkyl; R2 is hydrogen, C1-6alkyl, perhalomethylC0-5alkyl-O-, or C1-6alkoxy; R3 is hydrogen, C1-6alkyl, or C1-6alkoxyC1-6alkyl; R4 is hydrogen, C1-6alkyl, perhalomethylC1-6alkyl; or unsubstituted C3-6cycloalkylC1-6alkyl; A is C-R5 or N; B is C-R6 or N; D is C-R7 or N; with the proviso that at least one of A, B, and D, is N; R5 is hydrogen or C1-6alkyl; R6 is hydrogen or C1-6alkyl; R7 is hydrogen, C1-6alkyl, C1-6alkoxy, or hydroxy; R8 is hydrogen or C1-6alkyl, with the proviso that one of R4 and R8 is hydrogen; R9 is hydrogen or hydroxy; R10 is hydrogen or C1-6alkyl; and salts thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis.

  式（I）的化合物，其中; R1为氢或C1-6烷基; R2为氢，C1-6烷基，全氟甲基C0-5烷基-O-，或C1-6烷氧基; R3为氢，C1-6烷基，或C1-6烷氧基C1-6烷基; R4为氢，C1-6烷基，全氟甲基C1-6烷基; 或未取代的C3-6环烷基C1-6烷基; A为C-R5或N; B为C-R6或N; D为C-R7或N; 但A、B和D中至少有一个为N; R5为氢或C1-6烷基; R6为氢或C1-6烷基; R7为氢，C1-6烷基，C1-6烷氧基，或羟基; R8为氢或C1-6烷基，但R4和R8中至少有一个为氢; R9为氢或羟基; R10为氢或C1-6烷基; 其盐是PAD4抑制剂，可能对多种疾病的治疗有用，例如类风湿关节炎、血管炎、系统性红斑狼疮、溃疡性结肠炎、癌症、囊性纤维化、哮喘、皮肤性红斑狼疮和银屑病。
• 2-(azaindol-2-yl)benzimidazoles as PAD4 inhibitors
  申请人：Atkinson Stephen John

  公开号：US09127003B2

  公开（公告）日：2015-09-08

  Compounds of formula (I): wherein; R1 is hydrogen or C1-6alkyl; R2 is hydrogen, C1-6alkyl, perhalomethylC0-5alkyl-O—, or C1-6alkoxy; R3 is hydrogen, C1-6alkyl, or C1-6alkoxyC1-6alkyl; R4 is hydrogen, C1-6alkyl, perhalomethylC1-6alkyl; or unsubstituted C3-6cycloalkylC1-6 alkyl; A is C—R5 or N; B is C—R6 or N; D is C—R7 or N; with the proviso that at least one of A, B, and D, is N; R5 is hydrogen or C1-6alkyl; R6 is hydrogen or C1-6alkyl; R7 is hydrogen, C1-6alkyl, C1-6alkoxy, or hydroxy; R8 is hydrogen or C1-6alkyl, with the proviso that one of R4 and R8 is hydrogen; R9 is hydrogen or hydroxy; R10 is hydrogen or C1-6alkyl; and salts thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis.

  化合物的公式（I）：其中；R1是氢或C1-6烷基；R2是氢，C1-6烷基，全氟甲基C0-5烷氧基，或C1-6烷氧基；R3是氢，C1-6烷基或C1-6烷氧基C1-6烷基；R4是氢，C1-6烷基，全氟甲基C1-6烷基；或未取代的C3-6环烷基C1-6烷基；A是C-R5或N；B是C-R6或N；D是C-R7或N；但至少其中一个为N；R5是氢或C1-6烷基；R6是氢或C1-6烷基；R7是氢，C1-6烷基，C1-6烷氧基或羟基；R8是氢或C1-6烷基，但R4和R8中至少有一个是氢；R9是氢或羟基；R10是氢或C1-6烷基；其盐是PAD4抑制剂，可用于治疗各种疾病，例如类风湿性关节炎，血管炎，系统性红斑狼疮，溃疡性结肠炎，癌症，囊性纤维化，哮喘，皮肤性红斑狼疮和银屑病。
• 2 - (AZAINDOL-2-YL) BENZ IMIDAZOLES AS PAD4 INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：US20160009716A1

  公开（公告）日：2016-01-14

  Compounds of formula (I) wherein; R 1 is hydrogen or C 1-6 alkyl; R 2 is hydrogen, C 1-6 alkyl, perhalomethylC 0-5 alkyl-O—, or C 1-6 alkoxy; R 3 is hydrogen, C 1-6 alkyl, or C 1-6 alkoxyC 1-6 alkyl; R 4 is hydrogen, C 1-6 alkyl, perhalomethylC 1-6 alkyl; or unsubstituted C 3-6 cycloalkylC 1-6 alkyl; A is C—R 5 or N; B is C—R 6 or N; D is C—R 7 or N; with the proviso that at least one of A, B, and D, is N; R 5 is hydrogen or C 1-6 alkyl; R 6 is hydrogen or C 1-6 alkyl; R 7 is hydrogen, C 1-6 alkyl, C 1-6 alkoxy, or hydroxy; R 8 is hydrogen or C 1-6 alkyl, with the proviso that one of R 4 and R 8 is hydrogen; R 9 is hydrogen or hydroxy; Rio is hydrogen or C 1-6 alkyl; and salts thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis.

  化合物的公式（I）其中; R1是氢或C1-6烷基; R2是氢，C1-6烷基，全卤甲基C0-5烷基-O-，或C1-6烷氧基; R3是氢，C1-6烷基或C1-6烷氧基C1-6烷基; R4是氢，C1-6烷基，全卤甲基C1-6烷基; 或未取代的C3-6环烷基C1-6烷基; A是C-R5或N; B是C-R6或N; D是C-R7或N; 前提是A，B和D中至少有一个是N; R5是氢或C1-6烷基; R6是氢或C1-6烷基; R7是氢，C1-6烷基，C1-6烷氧基或羟基; R8是氢或C1-6烷基，前提是R4和R8中的一个是氢; R9是氢或羟基; Rio是氢或C1-6烷基; 其盐是PAD4抑制剂，可能在治疗各种疾病方面有用，例如类风湿性关节炎，血管炎，系统性红斑狼疮，溃疡性结肠炎，癌症，囊性纤维化，哮喘，皮肤红斑性狼疮和银屑病。
• PEPTIDYLARGININE DEIMINASE INHIBITOR AND USE THEREOF
  申请人：Nanjing Transthera Biosciences Co., Ltd.

  公开号：EP3760628A1

  公开（公告）日：2021-01-06

  The present invention relates to the technical field of pharmaceuticals, and particularly to a peptidylarginine deiminase (PAD4) inhibitor compound of formula (I) or a pharmaceutically acceptable salt, stereoisomer and tautomer thereof, and pharmaceutical composition, pharmaceutical formulation and use thereof. X, Y, R1, R2, R3, R4, R5, R7, R8, R9, ring B and m are defined in the specification. The compound disclosed herein has an inhibitory effect on peptidylarginine deiminase (PAD4), and can be used to treat a variety of diseases, such as rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, multiple sclerosis, cystic fibrosis, cancer, cutaneous lupus erythematosus, asthma and psoriasis.

  本发明涉及医药技术领域，尤其涉及一种式（I）的肽基精氨酸脱氨酶（PAD4）抑制剂化合物或其药学上可接受的盐、立体异构体和同系物及其药物组合物、药物制剂和用途。X、Y、R1、R2、R3、R4、R5、R7、R8、R9、环 B 和 m 在说明书中定义。本文公开的化合物对肽基精氨酸脱氨酶（PAD4）具有抑制作用，可用于治疗多种疾病，如类风湿性关节炎、血管炎、系统性红斑狼疮、溃疡性结肠炎、多发性硬化症、囊性纤维化、癌症、皮肤红斑狼疮、哮喘和银屑病。
• 2-(azaindol-2-yl) benzimidazoles as PAD4 inhibitors
  申请人：Glaxo Group Limited

  公开号：US10039755B2

  公开（公告）日：2018-08-07

  Compounds of formula (I) wherein; R1 is hydrogen or C1-6alkyl; R2 is hydrogen, C1-6alkyl, perhalomethylC0-5alkyl-O—, or C1-6alkoxy; R3 is hydrogen, C1-6alkyl, or C1-6alkoxyC1-6alkyl; R4 is hydrogen, C1-6alkyl, perhalomethylC1-6alkyl; or unsubstituted C3-6cycloalkylC1-6alkyl; A is C—R5 or N; B is C—R6 or N; D is C—R7 or N; with the proviso that at least one of A, B, and D, is N; R5 is hydrogen or C1-6alkyl; R6 is hydrogen or C1-6alkyl; R7 is hydrogen, C1-6alkyl, C1-6alkoxy, or hydroxy; R8 is hydrogen or C1-6alkyl, with the proviso that one of R4 and R8 is hydrogen; R9 is hydrogen or hydroxy; R10 is hydrogen or C1-6alkyl; and salts thereof are PAD4 inhibitors and may be useful in the treatment of various disorders, for example rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis.

  式(I)化合物 其中；R1是氢或C1-6烷基；R2是氢、C1-6烷基、全卤甲基C0-5烷基-O-或C1-6烷氧基；R3是氢、C1-6烷基或C1-6烷氧基C1-6烷基；R4是氢、C1-6烷基、全卤甲基C1-6烷基；或未取代的 C3-6 环烷基 C1-6 烷基；A 是 C-R5 或 N；B 是 C-R6 或 N；D 是 C-R7 或 N；但 A、B 和 D 中至少有一个是 N；R5 是氢或 C1-6 烷基；R6 是氢或 C1-6 烷基；R7是氢、C1-6烷基、C1-6烷氧基或羟基； R8是氢或C1-6烷基，但条件是R4和R8之一是氢； R9是氢或羟基； R10是氢或C1-6烷基；及其盐类是 PAD4 抑制剂，可用于治疗各种疾病，例如类风湿性关节炎、血管炎、系统性红斑狼疮、溃疡性结肠炎、癌症、囊性纤维化、哮喘、皮肤红斑狼疮和银屑病。