2-(2-(1-allyloxycarbonylamino-isoquinolin-6-oxy)-ethyl)-piperidine | 266690-90-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 2-(2-(1-allyloxycarbonylamino-isoquinolin-6-oxy)-ethyl)-piperidine
• 英文别名: prop-2-enyl N-[6-(2-piperidin-2-ylethoxy)isoquinolin-1-yl]carbamate
• CAS: 266690-90-8
• 化学式: C₂₀H₂₅N₃O₃
• 分子量: 355.437
• InChiKey: HHICNYYLNUAXTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  72.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-allyloxycarbonyl-N-tert-butoxycarbonylmethyl-D-cyclohexylalanine 、 2-(2-(1-allyloxycarbonylamino-isoquinolin-6-oxy)-ethyl)-piperidine 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以57%的产率得到1-(N-allyloxycarbonyl-N-tert-butoxycarbonylmethyl-D-cyclohexylalaninyl)-2-(2-(1-allyloxycarbonylamino-isoquinolin-6-oxy)-ethyl)-piperidine
  参考文献：
  名称：

  Serine protease inhibitor

  摘要：

  具有以下式(I)的丝氨酸蛋白酶抑制剂， 其中J是H、R1、R1—O—C(O)—、R1—C(O—、R1—SO2—、R3OOC—(CHR2)p—、(R2a,R2b)N—CO—(CHR2)p—或Het-CO—(CHR2)p—； W是具有以下式的氨基酸—NH—CHR1—C(O)—、—NR4—CH((CH2)qC(O)OR1)—C(O)—、—NR4—CH((CH2)qC(O)N(R2a,R2b))—C(O)—、—NR4—CH((CH2)qC(O)Het)-C(O)—、D-1-Tiq、D-3-Tiq、D-Atc、Aic、D-1-Piq、D-3 Piq、谷氨酰基或其(C1-C6)烷基酯； E是—NR2—CH2—或未被(1-6C)烷基、(1-6C)烷氧基或苄氧基取代的片段； R1从(1-12C)烷基、(2-12C)烯基、(2-12C)炔基、(3-12C)环烷基和(3-12C)环烷基(1-6C)烷基中选择，这些基团未被(3-12C)环烷基、(1-6C)烷氧基、氧化物、OH、CF3或卤素取代，以及从(6-14C)芳基、(7-15C)芳基烷基、(8-16C)芳基烯基和(14-20C)(双芳基)烷基中选择，其中芳基未被(1-6C)烷基、(3-12C)环烷基、(1-6C)烷氧基、OH、CF3或卤素取代； R2、R2a和R2b各自独立选择自H、(1-C)烷基、(3-8C)烯基、(3-8C)炔基、(3-8C)环烷基和(3-6C)环烷基(1-4C)烷基，这些基团未被(3-6C)环烷基、(1-6C)烷氧基、CF3或卤素取代，以及从(6-14C)芳基和(7-15C)芳基烷基中选择，其中芳基未被(1-6C)烷基、(3-6C)环烷基、(1-6C)烷氧基、CF3或卤素取代； R3与R2相同或为Het-(1-6C)烷基； R4为H或(1-3C)烷基； X和Y为CH或N，但它们不同时为N； Het是含有来自O、N和S的一个或多个杂原子的4、5或6元杂环； m为1或2； p为1、2或3； q为1、2或3； t为2、3或4； 或其药学上可接受的加合盐或溶剂。

  公开号：

  US06903107B1

文献信息

• SERINE PROTEASE INHIBITOR
  申请人：Akzo Nobel N.V.

  公开号：EP1123280A1

  公开（公告）日：2001-08-16
• US6903107B1
  申请人：——

  公开号：US6903107B1

  公开（公告）日：2005-06-07
• [EN] SERINE PROTEASE INHIBITOR<br/>[FR] INHIBITEUR DE LA SERINE PROTEASE
  申请人：AKZO NOBEL NV

  公开号：WO2000024718A1

  公开（公告）日：2000-05-04

  The invention relates to a serine protease inhibitor having formula (I), in which J is H, R1, R1-O-C(O)-, R1-C(O)-, R1-SO2-, R3OOC-(CHR2)p-, (R2a, R2b)N-CO-(CHR2)p- or Het-CO-(CHR2)p-; D is an amino-acid of the formula -NH-CHR1-C(O)-, -NR4-CH[(CH¿2?)qC(O)OR?1¿]-C(O)-, -NR4-CH[(CH¿2?)qC(O)N(R?2a,R2b¿)]-C(O)-, -NR4-CH[(CH¿2?)qC(O)Het]-C(O)-, D-1-Tiq, D-3-Tiq, D-Atc, Aic, D-1-Piq or D 3-Piq; E is -NR?2-CH¿2 or the fragment (a), optionally substituted with (1-6C)alkyl, (1-6C)alkoxy or benzyloxy; R1 is selected from (1-12C)alkyl, (2-12C)alkenyl, (2-12C)alkynyl, (3-12C)cycloalkyl and (3-12C)cycloalkyl(1-6C)alkylene, which groups may optionally be substituted with (3-12C)cycloalkyl, (1-6C)alkoxy, oxo, OH, CF¿3? or halogen, and from (6-14C)aryl, (7-15C)aralkyl, (8-16C)aralkenyl and (14-20C)(bisaryl)alkyl, whereby the aryl groups may optionally be substituted with (1-6C)alkyl, (3-12C)cycloalkyl, (1-6C)alkoxy, OH, CF3 or halogen; R?2, R2a and R2b¿ are each independently selected from H, (1-8C)alkyl, (3-8C)alkenyl, (3-8C)alkynyl, (3-8C)cycloalkyl and (3-6C)cycloalkyl(1-4C)alkylene, which can each be optionally substituted with (3-6C)cycloalkyl, (1-6C)alkoxy, CF¿3? or halogen, and from (6-14C)aryl and (7-15C)aralkyl whereby the aryl groups may optionally be substituted with (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, CF3 or halogen; R?3¿ is defined for R2 or Het-(1-6C)alkyl; R4 is H or (1-3C)alkyl; X and Y are CH or N with the proviso that they are not both N; Het is a 4-, 5- or 6-membered heterocycle containing one or more heteroatoms selected from O, N and S; m is 1 or 2; p is 1, 2 or 3; q is 1, 2 or 3; t is 2, 3 or 4; or a prodrug; or a pharmaceutically acceptable addition salt and/or solvate thereof and its use in therapy and manufacture of a medicament for treating or preventing thrombin-mediated and thrombin-associated diseases.
• Serine protease inhibitor
  申请人：Timmers Cornelis Marius

  公开号：US06903107B1

  公开（公告）日：2005-06-07

  A serine protease inhibitor having the formula (I), in which J is H, R 1 , R 1 —O—C(O)—, R 1 —C(O—, R 1 —SO 2 —, R 3 OOC—(CHR 2 ) p —, (R 2a ,R 2b )N—CO—(CHR 2 ) p — or Het-CO—(CHR 2 ) p —; W is an amino-acid of the formula —NH—CHR 1 —C(O)—, —NR 4 —CH((CH 2 ) q C(O)OR 1 )—C(O)—, —NR 4 —CH((CH 2 ) q C(O)N(R 2a ,R 2b ))—C(O)—, —NR 4 —CH((CH 2 ) q C(O)Het)-C(O)—, D-1-Tiq, D-3-Tiq, D-Atc, Aic, D-1-Piq, D-3 Piq, glutanyl or a (C 1 -C 6 ) alkylester thereof; E is —NR 2 —CH 2 — or the fragment which is unsubstituted or substituted with (1-6C)alkyl, (1-6C)alkoxy or benzyloxy; R 1 is selected form (1-12C)alkyl, (2-12C)alkenyl, (2-12C)alkynyl, (3-12C)cycloalkyl and (3-12C)cycloalkyl(1-6C)alkylene, which groups are unsubstituted or substituted with (3-12C)cycloalkyl, (1-6C)alkoxy, oxo, OH, CF 3 or halogen, and from (6-14C)aryl, (7-15C)aralkyl, (8-16C)aralkenyl and (14-20C)(bisary)alkyl, wherein the aryl groups are unsubstituted or substituted with (1-6C)alkyl, (3-12C)cycloalkyl, (1-6C)alkoxy, OH, CF 3 or halogen; R 2 , R 2a and R 2b are each independently selected from H, (1-C)alkyl, (3-8C)alkenyl, (3-8C)alkynyl, (3-8C)cycloalkyl and (3-6C)cycloalkyl(1-4C)alkylene, which are unsubstituted or substituted with (3-6C)cycloalkyl, (1-6C)alkoxy, CF 3 or halogen, and from (6-14C)aryl and (7-15C)aralkyl, wherein the aryl groups are unsubstituted or substituted with (1-6C)alkyl, (3-6C)cycloalkyl, (1-6C)alkoxy, CF 3 or halogen; R 3 is the same as R 2 or is Het-(1-6C)alkyl; R 4 is H or (1-3C)alkyl; X and Y are CH or N, with the proviso that they are not both N; Het is a 4-, 5- or 6-membered heterocycle containing one or more heteroatoms selected from O, N and S; m is 1 or 2; p is 1, 2 or 3; q is 1, 2 or 3; t is 2, 3 or 4; or a pharmaceutically acceptable addition salt or solvate thereof.

  具有以下式(I)的丝氨酸蛋白酶抑制剂， 其中J是H、R1、R1—O—C(O)—、R1—C(O—、R1—SO2—、R3OOC—(CHR2)p—、(R2a,R2b)N—CO—(CHR2)p—或Het-CO—(CHR2)p—； W是具有以下式的氨基酸—NH—CHR1—C(O)—、—NR4—CH((CH2)qC(O)OR1)—C(O)—、—NR4—CH((CH2)qC(O)N(R2a,R2b))—C(O)—、—NR4—CH((CH2)qC(O)Het)-C(O)—、D-1-Tiq、D-3-Tiq、D-Atc、Aic、D-1-Piq、D-3 Piq、谷氨酰基或其(C1-C6)烷基酯； E是—NR2—CH2—或未被(1-6C)烷基、(1-6C)烷氧基或苄氧基取代的片段； R1从(1-12C)烷基、(2-12C)烯基、(2-12C)炔基、(3-12C)环烷基和(3-12C)环烷基(1-6C)烷基中选择，这些基团未被(3-12C)环烷基、(1-6C)烷氧基、氧化物、OH、CF3或卤素取代，以及从(6-14C)芳基、(7-15C)芳基烷基、(8-16C)芳基烯基和(14-20C)(双芳基)烷基中选择，其中芳基未被(1-6C)烷基、(3-12C)环烷基、(1-6C)烷氧基、OH、CF3或卤素取代； R2、R2a和R2b各自独立选择自H、(1-C)烷基、(3-8C)烯基、(3-8C)炔基、(3-8C)环烷基和(3-6C)环烷基(1-4C)烷基，这些基团未被(3-6C)环烷基、(1-6C)烷氧基、CF3或卤素取代，以及从(6-14C)芳基和(7-15C)芳基烷基中选择，其中芳基未被(1-6C)烷基、(3-6C)环烷基、(1-6C)烷氧基、CF3或卤素取代； R3与R2相同或为Het-(1-6C)烷基； R4为H或(1-3C)烷基； X和Y为CH或N，但它们不同时为N； Het是含有来自O、N和S的一个或多个杂原子的4、5或6元杂环； m为1或2； p为1、2或3； q为1、2或3； t为2、3或4； 或其药学上可接受的加合盐或溶剂。