4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile | 1013210-85-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: 4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
• CAS: 1013210-85-9
• 化学式: C₈H₈N₂S
• 分子量: 164.231
• InChiKey: WNLIKVFSYPJDJI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile 、 N-(4-bromo-2,6-dimethylphenyl)-3,3-dimethylbutanamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 甲苯 为溶剂， 以29%的产率得到N-(4-(2-cyano-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2,6-dimethylphenyl)-3,3-dimethylbutanamide
  参考文献：
  名称：

  Design, synthesis and evaluation of novel N-phenylbutanamide derivatives as KCNQ openers for the treatment of epilepsy

  摘要：

  KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro and in vivo. Several compounds were found to be potent KCNQ openers. Compound 1 with favorable in vitro activity was submitted to evaluation in vivo. Results showed that compound 1 owned significant anti-convulsant activity with no adverse effects. It was also found to posses favorable pharmacokinetic profiles in rat. This research may provide novel potent compounds for the discovery of KCNQ openers in treating epilepsy.

  DOI：

  10.1016/j.bmcl.2018.05.019
• 作为产物：
  描述：

  N-(benzothiazole-2-sulfonyl)-2-cyano-4,5,6,7-tetrahydrothieno[3.2-c]pyridine 在 potassium carbonate 、 苯硫酚 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carbonitrile
  参考文献：
  名称：

  Synthesis of 4,5,6,7-tetrahydrothieno[3,2-c]pyridines and comparison with their isosteric 1,2,3,4-tetrahydroisoquinolines as inhibitors of phenylethanolamine N-methyltransferase

  摘要：

  A series of substituted 4,5,6,7-tetrahydrothieno[3,2-c]pyridines (THTPs) was synthesized and evaluated for their human phenylethanolamine N-methyltransferase (hPNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. The THTP nucleus was suggested as an isosteric replacement for the 1,2,3,4-tetrahydroisoquinoline (THIQ) ring system on the basis that 3-thienylmethylamine (18) was more potent as an inhibitor of hPNMT and more selective toward the alpha(2)-adrenoceptor than benzylamine (15). Although the isosterism was confirmed, with similar influence of functional groups and chirality in both systems on hPNMT inhibitory potency and selectivity, the THTP compounds proved, in general, to be less potent as inhibitors of hPNMT than their THIQ counterparts, with the drop in potency being primarily attributed to the electronic properties of the thiophene ring. A hypothesis for the reduced hPNMT inhibitory potency of these compounds has been formed on the basis of molecular modeling and docking studies using the X-ray crystal structures of hPNMT co-crystallized with THIQ-type inhibitors and S-adenosyl-L-homocysteine as a template. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.08.066

文献信息

• [EN] FUSED HETEROCYCLYL DERIVATIVES AS NAMPT INHIBITORS<br/>[FR] DÉRIVÉS HÉTÉROCYCLYLES FUSIONNÉS EN TANT QU'INHIBITEURS NAMPT
  申请人：AURIGENE DISCOVERY TECH LTD

  公开号：WO2014141035A2

  公开（公告）日：2014-09-18

  The present invention provides substituted heterocyclyl derivatives of formula (I), which may be therapeutically useful, more particularly as NAMPT inhibitors; in which R1, R2, X1, X2, ring A, L and 'n' have the meanings given in the specification, and pharmaceutically acceptable salts thereof that are useful in the treatment and prevention of diseases or disorder caused by an elevated level of nicotinamide phosphoribosyltransferase (NAMPT) in a mammal. The present invention also provides preparation of the compounds and pharmaceutical formulations comprising at least one of the substituted fused heterocyclyl derivatives of formula (I) or pharmaceutically acceptable salts or stereoisomers thereof.
• Synthesis of 4,5,6,7-tetrahydrothieno[3,2-c]pyridines and comparison with their isosteric 1,2,3,4-tetrahydroisoquinolines as inhibitors of phenylethanolamine N-methyltransferase
  作者：Gary L. Grunewald、Mitchell R. Seim、Seema R. Bhat、Marc E. Wilson、Kevin R. Criscione

  DOI：10.1016/j.bmc.2007.08.066

  日期：2008.1

  A series of substituted 4,5,6,7-tetrahydrothieno[3,2-c]pyridines (THTPs) was synthesized and evaluated for their human phenylethanolamine N-methyltransferase (hPNMT) inhibitory potency and affinity for the alpha(2)-adrenoceptor. The THTP nucleus was suggested as an isosteric replacement for the 1,2,3,4-tetrahydroisoquinoline (THIQ) ring system on the basis that 3-thienylmethylamine (18) was more potent as an inhibitor of hPNMT and more selective toward the alpha(2)-adrenoceptor than benzylamine (15). Although the isosterism was confirmed, with similar influence of functional groups and chirality in both systems on hPNMT inhibitory potency and selectivity, the THTP compounds proved, in general, to be less potent as inhibitors of hPNMT than their THIQ counterparts, with the drop in potency being primarily attributed to the electronic properties of the thiophene ring. A hypothesis for the reduced hPNMT inhibitory potency of these compounds has been formed on the basis of molecular modeling and docking studies using the X-ray crystal structures of hPNMT co-crystallized with THIQ-type inhibitors and S-adenosyl-L-homocysteine as a template. (c) 2007 Elsevier Ltd. All rights reserved.
• Design, synthesis and evaluation of novel N-phenylbutanamide derivatives as KCNQ openers for the treatment of epilepsy
  作者：Shaoning Yang、Dingqiang Lu、Pingkai Ouyang

  DOI：10.1016/j.bmcl.2018.05.019

  日期：2018.9

  KCNQ (Kv7) has emerged as a validated target for the development of novel anti-epileptic drugs. In this paper, a series of novel N-phenylbutanamide derivatives were designed, synthesized and evaluated as KCNQ openers for the treatment of epilepsy. These compounds were evaluated for their KCNQ opening activity in vitro and in vivo. Several compounds were found to be potent KCNQ openers. Compound 1 with favorable in vitro activity was submitted to evaluation in vivo. Results showed that compound 1 owned significant anti-convulsant activity with no adverse effects. It was also found to posses favorable pharmacokinetic profiles in rat. This research may provide novel potent compounds for the discovery of KCNQ openers in treating epilepsy.