2-(cyclopropylmethyl)-1H-benzo[d]imidazole | 1249112-58-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-(cyclopropylmethyl)-1H-benzo[d]imidazole
• 英文别名: 2-(cyclopropylmethyl)-1H-benzimidazole
• CAS: 1249112-58-0
• 化学式: C₁₁H₁₂N₂
• 分子量: 172.23
• InChiKey: CGMDFQJABKJUGX-UHFFFAOYSA-N

物化性质

• 沸点：
  384.4±11.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(1-((2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)methyl)-piperidin-4-yl)propan-2-ol 、 2-(cyclopropylmethyl)-1H-benzo[d]imidazole 以to give 308的产率得到2-(1-((2-(2-(cyclopropylmethyl)-1H-benzo[d]imidazol-1-yl)-9-methyl-6-morpholino-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol
  参考文献：
  名称：

  BICYCLIC PYRIMIDINE PI3K INHIBITOR COMPOUNDS SELECTIVE FOR P110 DELTA, AND METHODS OF USE

  摘要：

  Formula I（Ia和Ib）化合物中，其中（i）X1为N且X2为S，（ii）X1为CR7且X2为S，（iii）X1为N且X2为NR2，或（iv）X1为CR7且X2为0，包括立体异构体，互变异构体，代谢物和药学上可接受的盐，有用于抑制PI3K的δ异构体，并用于治疗由脂质激酶介导的疾病，例如炎症，免疫和癌症。公开了使用Formula I化合物的方法，用于哺乳动物细胞中的体外，体内和原位诊断，预防或治疗此类疾病或相关病理条件。

  公开号：

  US20120178736A1
• 作为产物：
  描述：

  环丙乙酸 、 邻苯二胺 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 4.0h， 以24%的产率得到2-(cyclopropylmethyl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Discovery of Dual Inducible/Neuronal Nitric Oxide Synthase (iNOS/nNOS) Inhibitor Development Candidate 4-((2-Cyclobutyl-1H-imidazo[4,5-b]pyrazin-1-yl)methyl)-7,8-difluoroquinolin-2(1H)-one (KD7332) Part 2: Identification of a Novel, Potent, and Selective Series of Benzimidazole-Quinolinone iNOS/nNOS Dimerization Inhibitors That Are Orally Active in Pain Models

  摘要：

  Three isoforms of nitric oxide synthase (NOS), dimeric enzymes that catalyze the formation of nitric oxide (NO) from arginine, have been identified. Inappropriate or excessive NO produced by iNOS and/or nNOS is associated with inflammatory and neuropathic pain. Previously, we described the identification of a series of amide-quinolinone iNOS dimerization inhibitors that although potent, suffered from high clearance and limited exposure in vivo. By conformationally restricting the amide of this progenitor series, we describe the identification of a novel series of benzimidazole-quinolinone dual iNOS/nNOS inhibitors with low clearance and sustained exposure in vivo. Compounds were triaged utilizing an LPS challenge assay coupled with mouse and rhesus pharmacokinetics and led to the identification of 4,7-imidazopyrazine 42 as the lead compound. 42 (KD7332) (J. Med. Chem. 2009, 52, 3047-3062) was confirmed as an iNOS dimerization inhibitor and was efficacious in the mouse formalin model of nociception and Chung model of neuropathic pain, without showing tolerance after repeat dosing. Further 42 did not affect motor coordination up to doses or 1000 mg/kg, demonstrating a wide therapeutic margin.

  DOI：

  10.1021/jm100828n

文献信息

• [EN] 1,2,4-OXADIAZOLE SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS SMO ANTAGONISTS<br/>[FR] DÉRIVÉS DE PIPÉRIDINE OU PIPÉRAZINE SUBSTITUÉS PAR 1,2,4-OXADIAZOLE COMME ANTAGONISTES DE SMO
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2010013037A1

  公开（公告）日：2010-02-04

  The present invention relates to compounds of formula (I): and pharmaceutically acceptable salts, stereoisomers or tautomers thereof which are inhibitors of the Sonic Hedgehog pathway, in particular Smo antagonists. Thus the compounds of this invention are useful for the treatment of diseases associated with abnormal hedgehog pathway activation, including cancer, for example basal cell carcinoma, medulloblastoma, prostate, pancreatic, breast, colon, bone and small cell lung cancers, and cancers of the upper GI tract.

  本发明涉及式(I)的化合物及其药学上可接受的盐、立体异构体或互变异构体，这些化合物是Sonic Hedgehog途径的抑制剂，特别是Smo拮抗剂。因此，本发明的化合物对治疗与异常Hedgehog途径激活相关的疾病有用，包括癌症，例如基底细胞癌、髓母细胞瘤、前列腺、胰腺、乳腺、结肠、骨骼和小细胞肺癌，以及上消化道的癌症。
• [EN] BICYCLIC PYRIMIDINE PI3K INHIBITOR COMPOUNDS SELECTIVE FOR P110 DELTA, AND METHODS OF USE<br/>[FR] COMPOSÉS PYRIMIDINES BICYCLIQUES INHIBITEURS DE PI3K SÉLECTIFS POUR P110 DELTA, ET PROCÉDÉS D'UTILISATION
  申请人：GENENTECH INC

  公开号：WO2010138589A1

  公开（公告）日：2010-12-02

  Formula (I) ((Ia) and (Ib)) compounds wherein (i) X1 is N and X2 is S, (ii) X1 is CR7 and X2 is S, (iii) X1 is N and X2 is NR2, or (iv) X1 is CR7 and X2 is O, including stereoisomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological, and cancer. Methods of using compounds of Formula (I) for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  公式（I）（（Ia）和（Ib））化合物，其中（i）X1为N且X2为S，（ii）X1为CR7且X2为S，（iii）X1为N且X2为NR2，或（iv）X1为CR7且X2为O，包括其立体异构体，互变异构体，代谢物和药用可接受盐，用于抑制PI3K的δ异构体，并用于治疗由脂质激酶介导的疾病，如炎症，免疫和癌症。公开了使用公式（I）化合物进行体外，体内和体内诊断，预防或治疗哺乳动物细胞中的这类疾病或相关病理状况的方法。
• BICYCLIC PYRIMIDINE PI3K INHIBITOR COMPOUNDS SELECTIVE FOR P110 DELTA, AND METHODS OF USE
  申请人：Castanedo Georgette

  公开号：US20120178736A1

  公开（公告）日：2012-07-12

  Formula I (Ia and Ib) compounds wherein (i) X 1 is N and X 2 is S, (ii) X 1 is CR 7 and X 2 is S, (iii) X 1 is N and X 2 is NR 2 , or (iv) X 1 is CR 7 and X 2 is 0, including stereoisomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

  Formula I（Ia和Ib）化合物中，其中（i）X1为N且X2为S，（ii）X1为CR7且X2为S，（iii）X1为N且X2为NR2，或（iv）X1为CR7且X2为0，包括立体异构体，互变异构体，代谢物和药学上可接受的盐，有用于抑制PI3K的δ异构体，并用于治疗由脂质激酶介导的疾病，例如炎症，免疫和癌症。公开了使用Formula I化合物的方法，用于哺乳动物细胞中的体外，体内和原位诊断，预防或治疗此类疾病或相关病理条件。
• Dibenzooxepin derivative
  申请人：Yamamoto Keisuke

  公开号：US08969345B2

  公开（公告）日：2015-03-03

  A dibenzoxepin derivative represented by the following general formula (I) wherein Y is a hydrogen atom and the like, RA is a hydrogen atom and the like, X is the formula (b3) wherein RB is a hydrogen atom and the like, and the like, A is the formula (a18) wherein R1 is a hydrogen atom and the like, and RC and RD are the same or different and each is a hydrogen atom and the like, and the like, which has a PPARγ agonist activity and the like, and useful as a therapeutic agent and/or prophylaxis agent and the like for type 2 diabetes and the like, or a pharmaceutically acceptable salt thereof and the like is provided.

  提供了一种二苯并氧吩衍生物，其通式表示为（I），其中Y为氢原子等，RA为氢原子等，X为式（b3），其中RB为氢原子等，A为式（a18），其中R1为氢原子等，RC和RD相同或不同，且每个为氢原子等，该物质具有PPARγ激动剂活性等，可用作治疗和/或预防2型糖尿病等的治疗剂和/或预防剂等，或其药学上可接受的盐等。
• DIBENZOOXEPIN DERIVATIVE
  申请人：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP2740730B1

  公开（公告）日：2016-11-16