benzothiazol-2-yl-pyrrolidin-2-yl-methanol | 689217-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: benzothiazol-2-yl-pyrrolidin-2-yl-methanol
• 英文别名: 1,3-benzothiazol-2-yl-[(2S)-pyrrolidin-2-yl]methanol
• CAS: 689217-71-8
• 化学式: C₁₂H₁₄N₂OS
• 分子量: 234.322
• InChiKey: KTBYWIHYWJDZIP-FTNKSUMCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  73.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzothiazol-2-yl-pyrrolidin-2-yl-methanol 在 草酰氯 、 1-羟基苯并三唑 、 二甲基亚砜 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 作用下， 反应 0.5h， 生成 2-<<1-<<1-(benzyloxycarbonyl)-2(S)-pyrrolidinyl>carbonyl>-2(S)-pyrrolidinyl>carbonyl>benzothiazole
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of Peptidyl .alpha.-Keto Heterocycles as Novel Inhibitors of Prolyl Endopeptidase

  摘要：

  The preparation and in vitro prolyl endopeptidase (PEP) inhibitory activity of a series of alpha-keto heterocyclic compounds is described. The design is based on the introduction of alpha-keto heterocycles at the C-terminal end of substrate-like peptides. Many of the compounds including those substituted with thiazole, benzothiazole, benzoxazole, imidazole, and pyridine groups exhibit IC50 potencies of PEP inhibition at nanomolar levels. Structure-activity studies of the C-terminal heterocyclic groups indicate the importance of an sp(2) nitrogen atom at a beta-position from the adjoining ketone carbonyl group. This heterocyclic nitrogen atom would provide a critical hydrogen-bond interaction with the histidine residue of the catalytic triad in PEP. Our inhibitors would extend the generality of the alpha-keto heterocycle design to another serine protease.

  DOI：

  10.1021/jm00047a007
• 作为产物：
  描述：

  (S)-N-Boc-吡咯烷-2-甲醛 N-(叔丁氧羰基)-L-脯氨醛 在 正丁基锂 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 benzothiazol-2-yl-pyrrolidin-2-yl-methanol
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of Peptidyl .alpha.-Keto Heterocycles as Novel Inhibitors of Prolyl Endopeptidase

  摘要：

  The preparation and in vitro prolyl endopeptidase (PEP) inhibitory activity of a series of alpha-keto heterocyclic compounds is described. The design is based on the introduction of alpha-keto heterocycles at the C-terminal end of substrate-like peptides. Many of the compounds including those substituted with thiazole, benzothiazole, benzoxazole, imidazole, and pyridine groups exhibit IC50 potencies of PEP inhibition at nanomolar levels. Structure-activity studies of the C-terminal heterocyclic groups indicate the importance of an sp(2) nitrogen atom at a beta-position from the adjoining ketone carbonyl group. This heterocyclic nitrogen atom would provide a critical hydrogen-bond interaction with the histidine residue of the catalytic triad in PEP. Our inhibitors would extend the generality of the alpha-keto heterocycle design to another serine protease.

  DOI：

  10.1021/jm00047a007

文献信息

• Novel compounds for the treatment of neurological disorders
  申请人：Niestroj J. Andre

  公开号：US20060100253A1

  公开（公告）日：2006-05-11

  The present invention relates to novel inhibitors of prolyl endopeptidase of formula 1 W—KCONH—X—CON—Y—CO—Z   (1) wherein K, W, X, Y and Z are specified in the description. The compounds are useful for the treatment of diseases such as mild cognitive impairment (MCI), Alzheimer's disease, Down Syndrome, Parkinson disease and Chorea Huntington.

  本发明涉及式 1 的新型脯氨酰内肽酶抑制剂 W-KCONH-X-CON-Y-CO-Z (1) 其中 K、W、X、Y 和 Z 在描述中具体说明。这些化合物可用于治疗轻度认知障碍（MCI）、阿尔茨海默病、唐氏综合症、帕金森病和亨廷顿舞蹈症等疾病。
• NOVEL COMPOUNDS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
  申请人：Probiodrug AG

  公开号：EP1824846A2

  公开（公告）日：2007-08-29
• US5547978A
  申请人：——

  公开号：US5547978A

  公开（公告）日：1996-08-20
• US7667044B2
  申请人：——

  公开号：US7667044B2

  公开（公告）日：2010-02-23
• [EN] NOVEL COMPOUNDS FOR THE TREATMENT OF NEUROLOGICAL DISORDERS<br/>[FR] NOUVEAUX COMPOSES POUR LE TRAITEMENT DE TROUBLES NEUROLOGIQUES
  申请人：PROBIODRUG AG

  公开号：WO2006058720A2

  公开（公告）日：2006-06-08

  [EN] The present invention relates to novel inhibitors of prolyl endopeptidase of formula (I): W-KCONH-X-CON-Y-CO-Z, wherein K, W; X, Y and Z are specified in the description. The compounds are useful for the treatment of diseases such as mild cognitive impairment (MCI), Alzheimer's disease. Down Syndrome, Parkinson disease and Chorea Huntington.
  [FR] La présente invention concerne de nouveaux inhibiteurs de propyl endopeptidase de formule (I), soit W-KCONH-X-CON-Y-CO-Z, dans laquelle K, W, X, Y et Z sont tels que définis dans la description. Ces composés sont utiles pour le traitement de maladies telles que la déficience cognitive bénigne (MCI), la maladie d'Alzheimer, le syndrome de Down, la maladie de Parkinson et la chorée de Huntington.