[1H-Indazol-3-yl]amide oxime | 131013-12-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: [1H-Indazol-3-yl]amide oxime
• 英文别名: N'-hydroxy-1H-indazole-3-carboximidamide
• CAS: 131013-12-2
• 化学式: C₈H₈N₄O
• 分子量: 176.178
• InChiKey: XDMBUJGOIRNEIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 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

反应信息

• 作为反应物：
  描述：

  1-氮杂双环[2.2.2]辛烷-3-羧酸甲酯 、 [1H-Indazol-3-yl]amide oxime 在 4 A molecular sieve 、 sodium hydride 作用下， 生成 3-[3-(1H-indazol-3-yl)-1,2,4-oxadiazol-5-yl]-1-azabicyclo[2.2.2]octane
  参考文献：
  名称：

  Novel 5-HT3 antagonists. Indole oxadiazoles

  摘要：

  The synthesis and biochemical evaluation of a series of indole oxadiazole 5-HT3 antagonists are described. The key pharmacophoric elements have been defined as a basic nitrogen, a linking group capable of H-bonding interactions, and an aromatic moiety. The steric limitations of the aromatic binding site have been determined by substitution about the indole ring. Variation of the heterocyclic linking group has shown that while two hydrogen-bonding interactions are possible, only one is essential for high affinity. The environment of the basic nitrogen has been investigated and shown to be optimal when constrained within an azabicyclic system. These results have been incorporated into a proposed binding model for the 5-HT3 antagonist binding site, in which the optimum distance between the aromatic binding site and the basic amine is 8.4-8.9 angstrom and the steric limitations are defined by van der Waals difference mapping.

  DOI：

  10.1021/jm00105a021
• 作为产物：
  描述：

  1H-吲唑-3-甲腈 在 吡啶 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 生成 [1H-Indazol-3-yl]amide oxime
  参考文献：
  名称：

  哌啶-螺恶二唑衍生物作为α7烟碱样受体拮抗剂的设计，合成和生物学活性。

  摘要：

  α 已经提出在神经和免疫系统中表达的7种烟碱乙酰胆碱受体（nAChRs）在炎症控制中起重要作用。然而，由于缺乏的拮抗剂工具特异性抑制α 7个的nAChR阻碍通道作为治疗靶的验证。要发现的选择性α 7拮抗剂，我们开始了基于药效的虚拟筛选和鉴定的哌啶衍生物spirooxadiazole T761 - 0184充当α 7拮抗剂。随后在非洲爪蟾卵母细胞中合成了一系列新型哌啶-螺二恶唑衍生物，并使用两电极电压钳（TEVC）分析对其进行了评估。两个系列的铅化合物均受抑制α7的IC 50值为3.3μM至13.7μM。化合物B10表现出α 7选择性超过其它α 4 β 2和α 3 β 4的nAChR亚型。的结构-活性关系的分析（SAR）提供了一种用于选择性的进一步发展了有价值的见解α 7的nAChR拮抗剂。

  DOI：

  10.1016/j.ejmech.2020.112774

文献信息

• Effect of heterocycle content on metal binding isostere coordination
  作者：Benjamin L. Dick、Ashay Patel、Seth M. Cohen

  DOI：10.1039/d0sc02717k

  日期：——

  retaining their metal binding and metalloenzyme inhibitory activity. Here, metal binding isosteres (MBIs) with different nitrogen-containing heteroarenes is explored. This resulted in a number of new MBIs that were evaluated for their physicochemical properties and metal binding features. It was observed that the coordination behavior of an MBI is dependent on the identity and arrangement of the heteroatoms

  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。
• Physiologically active 1,2,4,-oxa- and thiadiazoles
  申请人：Merck Sharp & Dohme Ltd.

  公开号：US04952587A1

  公开（公告）日：1990-08-28

  The present invention provides a compound of formula I or a salt or prodrug thereof: ##STR1## wherein the dotted circle represents one or two double bonds in any position in the 5-membered ring; X, Y and Z independently represent oxygen, sulphur, nitrogen or carbon, provided that at least one of X, Y and Z represents oxygen, sulphur or nitrogen; A represents a group of formula II: ##STR2## in which R.sup.1 represents hydrogen, hydroxy, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.1-6 alkoxy, hydroxy(C.sub.1-6)alkyl, halogen, amino, cyano, --CONR.sup.6 R.sup.7 or --SO.sub.2 NR.sup.6 R.sup.7, in which R.sup.6 and R.sup.7 independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; R.sup.2 represents hydrogen, halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy or C.sub.1-6 alkylcarbonyl; V represents nitrogen, ##STR3## and W represents oxygen, sulphur or ##STR4## in which R.sup.8 represents hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl; E represents a bond or a straight or branched alkylene chain containing from 1 to 5 carbon atoms, and optionally being substituted with hydroxy or phenyl; and F represents: (a) a non-aromatic azacyclic or azabicyclic ring system; or (b) a group of formula --NR.sup.a R.sup.b, in which R.sup.a and R.sup.b independently represent hydrogen, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl or aryl(C.sub.1-6)alkyl; which compounds are useful in the treatment of psychotic disorders (e.g. schizophrenia and mania); anxiety; alcohol or drug withdrawal; pain; gastric stasis; gastric dysfunction (such as occurs with dyspepsia, peptic ulcer, reflux oesophagitis and flatulence); migraine, nausea and vomiting; and presenile and senile dementia.

  本发明提供了化合物I的结构或其盐或前药：其中虚线圆圈代表5-成员环中任意位置的一个或两个双键；X、Y和Z独立地代表氧、硫、氮或碳，但至少一个X、Y和Z代表氧、硫或氮；A代表结构II的一个基团：其中R.sup.1代表氢、羟基、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基、C.sub.1-6烷氧基、羟基(C.sub.1-6)烷基、卤素、氨基、氰基、--CONR.sup.6 R.sup.7或--SO.sub.2 NR.sup.6 R.sup.7，其中R.sup.6和R.sup.7独立地代表氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；R.sup.2代表氢、卤素、C.sub.1-6烷基、C.sub.1-6烷氧基或C.sub.1-6烷基羰基；V代表氮，W代表氧、硫或其中R.sup.8代表氢、C.sub.1-6烷基、C.sub.2-6烯基或C.sub.2-6炔基；E代表键或含有1至5个碳原子的直链或支链烷基链，可选地被羟基或苯基取代；F代表：(a)非芳香性氮杂环或氮杂双环系统；或(b)结构--NR.sup.a R.sup.b的一个基团，其中R.sup.a和R.sup.b独立地代表氢、C.sub.1-6烷基、C.sub.2-6烯基、C.sub.2-6炔基或芳基(C.sub.1-6)烷基；这些化合物在治疗精神分裂症（例如精神分裂症和狂躁症）、焦虑、酒精或药物戒断、疼痛、胃排空延缓、胃功能障碍（如消化不良、消化性溃疡、反流性食道炎和胀气）、偏头痛、恶心呕吐以及老年性痴呆症等方面有用。
• SWAIN, C. J.;BAKER, R.;KNEEN, C.;MOSELEY, J.;SAUNDERS, J.;SEWARD, E. M.;S+, J. MED. CHEM., 34,(1991) N, C. 140-151
  作者：SWAIN, C. J.、BAKER, R.、KNEEN, C.、MOSELEY, J.、SAUNDERS, J.、SEWARD, E. M.、S+

  DOI：——

  日期：——
• Five-membered ring systems with bonded azacyclic ring substituents
  申请人：MERCK SHARP & DOHME LTD.

  公开号：EP0328200B1

  公开（公告）日：1993-12-08
• NEUE HETEROCYCLYLMETHYL-SUBSTITUIERTE PYRAZOLDERIVATE UND IHRE VERWENDUNG IN DER BEHANDLUNG VON HERZ-KREISLAUF-ERKRANKUNGEN
  申请人：Bayer HealthCare AG

  公开号：EP0934311B1

  公开（公告）日：2009-05-13