(2S)-1-[N-(tert-butyloxycarbonyl)-S-(3-picolylcarbamoylmethyl)-L-cysteinyl]pyrrolidine-2-carbonitrile | 371247-90-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S)-1-[N-(tert-butyloxycarbonyl)-S-(3-picolylcarbamoylmethyl)-L-cysteinyl]pyrrolidine-2-carbonitrile
• 英文别名: tert-butyl N-[(2R)-1-[(2S)-2-cyanopyrrolidin-1-yl]-1-oxo-3-[2-oxo-2-(pyridin-3-ylmethylamino)ethyl]sulfanylpropan-2-yl]carbamate
• CAS: 371247-90-4
• 化学式: C₂₁H₂₉N₅O₄S
• 分子量: 447.558
• InChiKey: HECTVGPOKFNKEW-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  31
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-1-[N-(tert-butyloxycarbonyl)-S-(3-picolylcarbamoylmethyl)-L-cysteinyl]pyrrolidine-2-carbonitrile 以 三氟乙酸 为溶剂， 生成 (2S)-1-[S-(3-picolylcarbamoylmethyl)-L-cysteinyl]pyrrolidine-2-carbonitrile trifluoroacetate
  参考文献：
  名称：

  Inhibitors of dipeptidyl peptidase IV

  摘要：

  根据通用公式（1），化合物中R1为H或CN，X1为S、O、SO2或CH2，X2为O、S或CH2，X3为NR5或羰基或硫代羰基基团，R4为R6R7N、R8(CH2)qOC（═O）、R8(CH2)qOC（═S）、R6R7NC(═O)、R6R7NC(═S)；R8(CH2)qC(═O)、R8(CH2)qC(═S)或R8(CH2)qSO2，m为1-3，n为0-4的新化合物。该发明的化合物是二肽基肽酶IV的抑制剂。该发明的化合物的药用组合物或其药用盐在治疗2型糖尿病等疾病中有用。

  公开号：

  US20030216450A1

文献信息

• Novel dipeptidyl peptidase iv (dp-iv) inhibitors as anti-diabetic agents
  申请人：Evans M David

  公开号：US20050004205A1

  公开（公告）日：2005-01-06

  The present invention relates to a series of prodrugs of inhibitors of DP-IV with improved properties. The compounds can be used for the treatment of a number of human diseases, including impaired glucose tolerance and type II diabetes. The compounds of the invention are described by general formula (1); wherein R 1 is H or CN; R 2 is selected from CH 2 R 5 , CH 2 CH 2 R 5 and C(R 3 )(R 4 )—X 2 —(CH 2 ) a R 5 ; R 3 and R 4 are each independently selected from H and Me; R 5 is selected from CON(R 6 )(R 7 ), N(R 8 )C(=0)R 9 , N(R 8 )C(═S)R 9 , N(R 8 )SO 2 R 10 and N(R 8 )R 10 ; R 6 and R 7 are each independently R 11 (CH 2 ) b or together they are —(CH 2 ) 2 -Z-(CH 2 ) 2 — or CH 2 -o-C 6 H 4 -Z-CH 2 —; R 8 is H or Me; R 9 is selected from R 11 (CH 2 ) b , R 11 (CH 2 ) b O and N(R 6 )(R 7 ); R 10 is R 11 (CH 2 ) b ; R 11 is selected from H, alkyl, optionally substituted aryl, optionally substituted aroyl, optionally substituted arylsulphonyl and optionally substituted heteroaryl; R 12 is selected from H 2 NCH(R 13 )CO, H 2 NCH(R 14 )CONHCH(R 15 )CO, C(R 16 )═C(R 17 )COR 18 and R 19 OCO; R 13 , R 14 and R 15 are selected from the side chains of the proteinaceous amino acids; R 16 is selected from H, lower alkyl (C 1 -C 6 ) and phenyl; R 17 is selected from H and lower alkyl (C 1 -C 6 ); R 18 is selected from H, lower alkyl (C 1 -C 6 ), OH, O-(lower alkyl (C 1 -C 6 )) and phenyl; R 19 is selected from lower alkyl (C 1 -C 6 ), optionally substituted phenyl and R 20 C(=0)OC(R 21 )(R 22 ); R 20 , R 21 and R 22 are each independently selected from H and lower alkyl (C 1 -C 6 ); Z is selected from a covalent bond, —(CH 2 ) c —, —O—, —SO d — and —N(R 10 )—; X 1 is S or CH 2 ; X 2 is O, S or CH 2 ; a is 1, 2 or 3; b is 0-3; c is 1 or 2; and d is 0, 1 or 2.

  本发明涉及一系列具有改进性能的DP-IV抑制剂的前药。这些化合物可用于治疗多种人类疾病，包括糖耐量受损和2型糖尿病。该发明的化合物由通式（1）描述；其中，R1为H或CN；R2选自 R5， R5和C（R3）（R4）-X2-（CH2）aR5；R3和R4各自独立地选自H和Me；R5选自CON（R6）（R7），N（R8）C（=0）R9，N（R8）C（═S）R9，N（R8）SO2R10和N（R8）R10；R6和R7各自独立地为R11（ ）b，或者它们为-（ ）2-Z-（ ）2-或 -o-C6H4-Z- -；R8为H或Me；R9选自R11（ ）b，R11（ ）bO和N（R6）（R7）；R10选自R11（ ）b；R11选自H，烷基，可选择取代的芳基，可选择取代的酰芳基，可选择取代的芳基磺酰基和可选择取代的杂环芳基；R12选自H2NCH（R13）CO，H2NCH（R14）CONHCH（R15）CO，C（R16）═C（R17）COR18和R19OCO；R13，R14和R15选自蛋白质氨基酸的侧链；R16选自H，低烷基（C1-C6）和苯基；R17选自H和低烷基（C1-C6）；R18选自H，低烷基（C1-C6），OH，O-（低烷基（C1-C6））和苯基；R19选自低烷基（C1-C6），可选择取代的苯基和R20C（=0）OC（R21）（R22）；R20，R21和R22各自独立地选自H和低烷基（C1-C6）；Z选自共价键，-（ ）c-，-O-，-SOd-和-N（R10）-；X1为S或 ；X2为O，S或 ；a为1、2或3；b为0-3；c为1或2；d为0、1或2。
• US7144886B2
  申请人：——

  公开号：US7144886B2

  公开（公告）日：2006-12-05
• US7189728B2
  申请人：——

  公开号：US7189728B2

  公开（公告）日：2007-03-13