2-amino-4-[[(1S)-1-(8-chloro-2-cyclopropyl-1-oxoisoquinolin-3-yl)ethyl]amino]pyrimidine-5-carbonitrile | 1425042-49-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2-amino-4-[[(1S)-1-(8-chloro-2-cyclopropyl-1-oxoisoquinolin-3-yl)ethyl]amino]pyrimidine-5-carbonitrile
• CAS: 1425042-49-4
• 化学式: C₁₉H₁₇ClN₆O
• 分子量: 380.837
• InChiKey: UIXGAIYKWMWQAY-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  6

文献信息

• HETEROCYCLIC COMPOUNDS AND USES THEREOF
  申请人：CASTRO Alfredo C.

  公开号：US20130053362A1

  公开（公告）日：2013-02-28

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein.

  本文描述了调节激酶活性的化合物和药物组合物，包括PI3激酶活性，以及与激酶活性相关的疾病和病况的治疗方法，包括PI3激酶活性的化合物、药物组合物和治疗方法。
• CERTAIN CHEMICAL ENTITIES, COMPOSITIONS AND METHODS
  申请人：Ren Pingda

  公开号：US20090312319A1

  公开（公告）日：2009-12-17

  Chemical entities that modulate PI3 kinase activity, pharmaceutical compositions containing the chemical entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.

  本文描述了调节PI3激酶活性的化学实体、含有这些化学实体的药物组合物，以及使用这些化学实体治疗与PI3激酶活性相关的疾病和病症的方法。
• PROCESS FOR PREPARING CERTAIN CHEMICAL ENTITIES
  申请人：Intellikine, LLC

  公开号：EP3150609A1

  公开（公告）日：2017-04-05

  A process for preparing a compound of formula: wherein R3 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, alkoxy, amido, amino, alkoxycarbonyl sulfonamido, halo, cyano, hydroxy or nitro, comprising reacting a compound of formula: with a compound of formula: in the presence of a base. The THP group may be removed with acid to make chemical entities that modulate PI3 kinase activity for treating diseases and conditions associated with PI3 kinase activity and/or formulated into pharmaceutical compositions containing such chemical entities.

  一种制备式化合物的工艺： 其中 R3 为氢、烷基、烯基、炔基、环烷基、杂环烷基、烷氧基、氨基、氨基、烷氧羰基磺酰胺基、卤代、氰基、羟基或硝基，包括将式： 与式 的化合物在碱存在下进行反应。THP基团可以用酸去除，制成调节PI3激酶活性的化学实体，用于治疗与PI3激酶活性相关的疾病和病症，和/或配制成含有此类化学实体的药物组合物。
• A PHARMACEUTICAL COMPOSITION FOR ORAL ADMINISTRATION
  申请人：Intellikine, LLC

  公开号：EP3441392A1

  公开（公告）日：2019-02-13

  A pharmaceutical composition for oral administration comprising an effective amount of a compound of Formula V-A2: or a pharmaceutically acceptable salt thereof; wherein B is a moiety of Formula II: Wc is aryl, heteroaryl, heterocycloalkyl, or cycloalkyl; q is an integer of 0 or 1; R1 is hydrogen, alkyl, or halo; R2 is alkyl or halo; R3 is halo; and R9 is alkyl, or heterocycloalkyl; and one or more pharmaceutically acceptable excipients suitable for oral administration. The pharmaceutical composition may contain an effective amount of a second agent such as a chemotherapeutic agent, e.g. a proteasome inhibitor, an alkylating agent or a therapeutic antibody.

  一种口服药物组合物，包含有效量的式 V-A2 化合物： 或其药学上可接受的盐； 其中 B 为式 II 的分子： Wc 是芳基、杂芳基、杂环烷基或环烷基； q 是 0 或 1 的整数； R1 是氢、烷基或卤素； R2 是烷基或卤代 R3 是卤代物；以及 R9 是烷基或杂环烷基； 以及一种或多种适合口服的药学上可接受的赋形剂。药物组合物可含有有效量的第二种药剂，如化疗药，如蛋白酶体抑制剂、烷化剂或治疗性抗体。
• TREATMENT OF CANCERS USING PI3 KINASE ISOFORM MODULATORS
  申请人：Infinity Pharmaceuticals, Inc.

  公开号：EP3811974A1

  公开（公告）日：2021-04-28

  Provided herein is a PI3K inhibitor, alone or in combination with one or more other therapeutic agents, for use in treating or managing indolent non-Hodgkin's lymphoma (iNHL) in a subject that is, or is identified as, relapsed or refractory to a prior treatment with rituximab and the iNHL is refractory to chemotherapy or radioimmunotherapy (RIP), wherein the PI3K inhibitor is Compound 292 or a pharmaceutically acceptable salt, a hydrate or a solvate thereof. Furthermore the application relates to a PI3K inhibitor, alone or in combination with one or more other therapeutic agents, for use in treating or managing cancer or hematologic malignancy in a subject who developed resistance to a prior treatment, wherein the PI3K inhibitor is Compound 292, or a pharmaceutically acceptable salt, a hydrate or a solvate thereof, and wherein the prior treatment is a treatment with one or more BTK inhibitors, anti-CD20 antibodies, proteasome inhibitors, or alkylating agents.

  本发明提供了一种PI3K抑制剂，单独或与一种或多种其它治疗剂联合，用于治疗或控制对先前利妥昔单抗治疗复发或难治，且iNHL对化疗或放射免疫治疗（RIP）难治的受试者中的懒惰性非霍奇金淋巴瘤（iNHL），其中PI3K抑制剂是化合物292或其药学上可接受的盐、水合物或溶液。此外，本申请还涉及一种PI3K抑制剂，单独或与一种或多种其它治疗剂联合使用，用于治疗或控制对先前治疗产生耐药性的受试者的癌症或血液恶性肿瘤，其中PI3K抑制剂是化合物292或其药学上可接受的盐、水合物或溶液，而先前的治疗是一种或多种BTK抑制剂、抗CD20抗体、蛋白酶体抑制剂或烷化剂的治疗。