n-羟基-1H-苯并咪唑-2-羧酰胺 | 14483-74-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 中文名称: n-羟基-1H-苯并咪唑-2-羧酰胺
• 英文名称: benzimidazole-2-carboxamide oxime
• 英文别名: N-hydroxy-1H-benzoimidazole-2-carboximidic acid amide；N'-hydroxy-1H-benzimidazole-2-carboximidamide；Benzimidazol-2-carbonsaeure-amidoxim；2-Benzimidazolylcarboxamidoxim；2-Benzimidazolcarboxamid-oxim；Benzimidazole-2-carboxamide oxime
• CAS: 14483-74-0
• 化学式: C₈H₈N₄O
• mdl: MFCD09751610
• 分子量: 176.178
• InChiKey: WHIQJYVDSGYHOS-UHFFFAOYSA-N

物化性质

• 沸点：
  412.3±28.0 °C(Predicted)
• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.3
• 氢给体数：
  3
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  n-羟基-1H-苯并咪唑-2-羧酰胺 在 盐酸 、 sodium nitrite 作用下， 生成
  参考文献：
  名称：

  Cundy, Darren J.; Simpson, Gregory W., Australian Journal of Chemistry, 1996, vol. 49, # 2, p. 199 - 204

  摘要：

  DOI：
• 作为产物：
  描述：

  1H-苯并咪唑-2-甲腈 在 羟胺 作用下， 生成 n-羟基-1H-苯并咪唑-2-羧酰胺
  参考文献：
  名称：

  杂环含量对金属结合等排配位的影响

  摘要：

  生物等排体替代是现代药物化学中的核心概念，并已被证明是解决治疗药效学和药代动力学限制的宝贵策略。生物等排体替代的成功通常取决于被修改的支架（即，“上下文依赖”）。最近证明了将生物等排体置换应用于吡啶甲酸片段作为扩展金属结合药效团 (MBP) 库以调节其物理化学性质，同时保持其金属结合和金属酶抑制活性的一种手段。在这里，探索了具有不同含氮杂芳烃的金属结合等排体 (MBI)。这导致了许多新的 MBI，它们的物理化学性质和金属结合特性被评估。据观察，MBI 的配位行为取决于每个杂芳烃内杂原子的特性和排列。为了进一步了解观察到的配位化学趋势，进行了密度泛函理论 (DFT) 计算。理论表明，配位几何的偏好很大程度上取决于杂芳烃支架的电子特性。这些结果为开发新型 MBI 支架提供了重要的见解，可以拓宽用于金属酶抑制剂开发的支架范围。

  DOI：

  10.1039/d0sc02717k

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] FURAZANOBENZIMIDAZOLES AS PRODRUGS TO TREAT NEOPLASTIC OR AUTOIMMUNE DISEASES<br/>[FR] FURAZANOBENZIMIDAZOLES EN TANT QUE PRÉCURSEURS DESTINÉS AU TRAITEMENT DE MALADIES NÉOPLASIQUES OU AUTO-IMMUNES
  申请人：BASILEA PHARMACEUTICA AG

  公开号：WO2011012577A1

  公开（公告）日：2011-02-03

  A compound of formula (II) wherein (a) represents a divalent benzene residue which is unsubstituted or substituted by one or two additional substituents independently selected from lower alkyl, halo-lower alkyl, hydroxy-lower alkyl, lower alkoxy-lower alkyl, acyloxy-lower alkyl, phenyl, hydroxy, lower alkoxy, hydroxy-lower alkoxy, lower alkoxy-lower alkoxy, phenyl-lower alkoxy, lower alkylcarbonyloxy, amino, mono(lower alkyl)amino, di(lower alkyl)amino, mono(lower alkenyl)amino, di(lower alkenyl)amino, lower alkoxycarbonylamino, lower alkylcarbonylamino, substituted amino wherein the two substituents on nitrogen form together with the nitrogen heterocyclyl, lower alkylcarbonyl, carboxy, lower 15 alkoxycarbonyl, cyano, halogen, and nitro; or wherein two adjacent substituents can be methylenedioxy; or a divalent pyridine residue (Z = N) which is unsubstituted or substituted additionally by lower alkyl, lower alkoxy, lower alkoxy-lower alkoxy,amino, optionally substituted by one or two substituents selected from lower alkyl, lower alkenyl and alkylcarbonyl, halo-20 lower alkyl, lower alkoxy-lower alkyl, or halogen; R1 represents hydrogen, lower alkylcarbonyl, hydroxy-lower alkylor cyano-loweralkyl; and R2 represents a group selected from: (b), (c) and (d); or pharmaceutically acceptable salts thereof.

  式（II）的化合物，其中（a）代表一个二价苯残基，该残基未取代或被一个或两个额外取代基独立选择自较低烷基、卤代较低烷基、羟基较低烷基、较低烷氧基较低烷基、酰氧较低烷基、苯基、羟基、较低烷氧基、羟基较低烷氧基、较低烷氧基较低烷氧基、苯基较低烷氧基、较低烷基羰基氧基、氨基、单（较低烷基）氨基、二（较低烷基）氨基、单（较低烯基）氨基、二（较低烯基）氨基、较低烷氧羰基氨基、较低烷基羰基氨基、取代氨基，其中氮上的两个取代基与氮一起形成杂环基、较低烷基羰基、羧基、较低烷氧羰基、氰基、卤素和硝基；或其中两个相邻的取代基可以是亚甲二氧基；或一个未取代或另外被较低烷基、较低烷氧基、较低烷氧基较低烷氧基、氨基、可选择地被较低烷基、较低烯基和烷基羰基、卤代较低烷基、较低烷氧基较低烷基或卤素中的一个或两个取代基取代的二价吡啶残基（Z = N）；R1代表氢、较低烷基羰基、羟基较低烷基或氰基较低烷基；R2代表从中选择的一组：（b）、（c）和（d）；或其药学上可接受的盐。
• Multiheterocyclic pharmAceuticals
  申请人：Bayer Aktiengesellschaft

  公开号：US06339083B1

  公开（公告）日：2002-01-15

  The present invention relates to compounds of the general formula (I): and their preparation and use for the production of pharmaceuticals, and pharmaceuticals comprising these compounds.

  本发明涉及一般式(I)的化合物，以及它们的制备和用于制药的生产，以及包含这些化合物的制药品。
• 1,2,4-OXADIAZOLE SUBSTITUTED PIPERIDINE AND PIPERAZINE DERIVATIVES AS SMO ANTAGONISTS
  申请人：Dessole Gabriella

  公开号：US20110183974A1

  公开（公告）日：2011-07-28

  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，其是Sonic Hedgehog通路的抑制剂，特别是Smo拮抗剂。因此，本发明的化合物对治疗与异常刺猬通路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，以及上消化道癌症。
• Identification of a series of 4-[3-(quinolin-2-yl)-1,2,4-oxadiazol-5-yl]piperazinyl ureas as potent smoothened antagonist hedgehog pathway inhibitors
  作者：Jesus M. Ontoria、Laura Llauger Bufi、Caterina Torrisi、Alberto Bresciani、Claudia Giomini、Michael Rowley、Sergio Serafini、Hu Bin、Wu Hao、Christian Steinkühler、Philip Jones

  DOI：10.1016/j.bmcl.2011.07.031

  日期：2011.9

  The Hedgehog (Hh-) signalling pathway is a key developmental pathway and there is a growing body of evidence showing that this pathway is aberrantly reactivated in a number of human tumors. Novel agents capable of inhibiting this pathway are sought, and an entirely novel series of smoothened (Smo) antagonists capable of inhibiting the pathway have been identified through uHTS screening. Extensive exploration of the scaffold identified the key functionalities necessary for potency, enabling potent nanomolar Smo antagonists like 91 and 94 to be developed. Optimization resulted in the most advanced compounds displaying low serum shift, clean off-targets profile, and moderate clearance in both rats and dogs. These compounds are valuable tools with which to probe the biology of the Hh-pathway. (C) 2011 Elsevier Ltd. All rights reserved.