2-chlorocarbonyloctahydroisoquinoline | 1257992-29-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-chlorocarbonyloctahydroisoquinoline
• 英文别名: 3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-2-carbonyl chloride
• CAS: 1257992-29-2
• 化学式: C₁₀H₁₆ClNO
• 分子量: 201.696
• InChiKey: VIVOMXGUBKHEPX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-chlorocarbonyloctahydroisoquinoline 、 N-[4-(piperazine-1-sulfonyl)phenyl]acrylamide 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 N-{4-[4-(octahydroisoquinoline-2-carbonyl)piperazine-1-sulfonyl]phenyl}acrylamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease

  摘要：

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.

  DOI：

  10.1021/jm201310y

文献信息

• INHIBITOR COMPOUNDS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1
  申请人：Catena Ruiz Juan Lorenzo

  公开号：US20120071466A1

  公开（公告）日：2012-03-22

  The compounds of formula (I) are derived from perhydroquinoline and perhydroisoquinoline and are useful as active pharmaceutical ingredients for the prophylaxis or treatment of diseases caused by 11-beta-hydroxysteroid dehydrogenase type I (11-beta-HSD1) enzyme-associated disorders, such as glaucoma, elevated ocular pressure, metabolic disorders, obesity, metabolic syndrome, dyslipidemia, hypertension, diabetes, atherosclerosis, Cushing's syndrome, psoriasis, rheumatoid arthritis, cognitive disorders, Alzheimer's disease or neurodegeneration.

  公式（I）的化合物是从过氢化喹啉和过氢化异喹啉衍生而来的，可用作预防或治疗由11-β-羟基类固醇脱氢酶I（11-β-HSD1）酶相关疾病引起的活性药用成分，如青光眼、眼压升高、代谢紊乱、肥胖、代谢综合征、脂质代谢异常、高血压、糖尿病、动脉粥样硬化、库欣综合征、银屑病、类风湿性关节炎、认知障碍、阿尔茨海默病或神经退行性疾病。
• US8524894B2
  申请人：——

  公开号：US8524894B2

  公开（公告）日：2013-09-03
• US8822452B2
  申请人：——

  公开号：US8822452B2

  公开（公告）日：2014-09-02
• [EN] INHIBITOR COMPOUNDS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE TYPE 1<br/>[ES] COMPUESTOS INHIBIDORES DE 11 BETA-HIDROXIESTEROIDE DESHIDROGENASE DE TIPO 1<br/>[FR] COMPOSÉS INHIBITEURS DE 11-BÊTA-HYDROXYSTÉROÏDE DÉSHYDROGÉNASE DE TYPE 1
  申请人：SALVAT LAB SA

  公开号：WO2010139827A1

  公开（公告）日：2010-12-09

  Los compuestos de fórmula (I) son derivados de perhidroquinolina y perhidroisoquinolina y son útiles como principios activos farmacéuticos para Ia profilaxis o tratamiento de enfermedades causadas por trastornos asociados con Ia enzima 11 beta-hidroxiesteroide deshidrogenasa de tipo 1 (11 beta- HSD1), tales como glaucoma, presión ocular elevada, trastornos metabólicos, obesidad, síndrome metabólico, dislipidemia, hipertensión, diabetes, aterosclerosis, síndrome de Cushing, psoriasis, artritis reumatoide, alteraciones de Ia cognición, enfermedad de Alzheimer o neurodegeneración.
• Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease
  作者：Michael E. Prime、Ole A. Andersen、John J. Barker、Mark A. Brooks、Robert K. Y. Cheng、Ian Toogood-Johnson、Stephen M. Courtney、Frederick A. Brookfield、Christopher J. Yarnold、Richard W. Marston、Peter D. Johnson、Siw F. Johnsen、Jordan J. Palfrey、Darshan Vaidya、Sayeh Erfan、Osamu Ichihara、Brunella Felicetti、Shilpa Palan、Anna Pedret-Dunn、Sabine Schaertl、Ina Sternberger、Andreas Ebneth、Andreas Scheel、Dirk Winkler、Leticia Toledo-Sherman、Maria Beconi、Douglas Macdonald、Ignacio Muñoz-Sanjuan、Celia Dominguez、John Wityak

  DOI：10.1021/jm201310y

  日期：2012.2.9

  Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.