1-{[((S)-cyclopentyloxycarbonyl-phenyl-methyl)-amino]-methyl}-1,3,4,9-tetrahydro-beta-carboline-2-carboxylic acid benzyl ester | 914604-95-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-{[((S)-cyclopentyloxycarbonyl-phenyl-methyl)-amino]-methyl}-1,3,4,9-tetrahydro-beta-carboline-2-carboxylic acid benzyl ester
• 英文别名: 1-{[((S)-Cyclopentyloxycarbonyl-phenyl-methyl)amino]-methyl}-1,3,4,9-tetrahydro-beta-carboline-2-carboxylic acid benzyl ester；benzyl 1-[[[(1S)-2-cyclopentyloxy-2-oxo-1-phenylethyl]amino]methyl]-1,3,4,9-tetrahydropyrido[3,4-b]indole-2-carboxylate
• CAS: 914604-95-8
• 化学式: C₃₃H₃₅N₃O₄
• 分子量: 537.659
• InChiKey: PZVFWMSGQWJAEO-ZSXSBBPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-{[((S)-cyclopentyloxycarbonyl-phenyl-methyl)-amino]-methyl}-1,3,4,9-tetrahydro-beta-carboline-2-carboxylic acid benzyl ester 在 palladium 10% on activated carbon 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 98.0h， 生成 (S)-[tert-butoxycarbonyl-(2,3,4,9-tetrahydro-1H-beta-carbolin-1-ylmethyl)-amino]-phenyl-acetic acid cyclopentyl ester
  参考文献：
  名称：

  WO2006/117549

  摘要：

  公开号：
• 作为产物：
  描述：

  色胺盐酸盐 在 氢氧化钾 、 sodium hydroxide 、 sodium acetate 、 二异丁基氢化铝 、 sodium cyanoborohydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 异丙醇 、 甲苯 为溶剂， 反应 13.5h， 生成 1-{[((S)-cyclopentyloxycarbonyl-phenyl-methyl)-amino]-methyl}-1,3,4,9-tetrahydro-beta-carboline-2-carboxylic acid benzyl ester
  参考文献：
  名称：

  WO2006/117549

  摘要：

  公开号：

文献信息

• ENZYME INHIBITORS
  申请人：Davidson Alan Hornsby

  公开号：US20140163042A1

  公开（公告）日：2014-06-12

  Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R 2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, —C(═O), —S(═O) 2 —, —C(═O)O—, —C(O)NR 3 —, —C(═S)—NR 3 , —C(═NH)NR 3 or —S(═O) 2 NR 3 — wherein R 3 is hydrogen or optionally substituted C 1 -C 6 alkyl; L 1 is a divalent radical of formula -(Alk 1 ) m (Q) n (Alk 2 ) p - wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula —X 2 -Q 1 - or -Q 1 -X 2 — wherein X 2 is —O—, S— or NR A — wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl, and Q 1 is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, Alk 1 and Alk 2 independently represent optionally substituted divalent C 3 -C 7 cycloalkyl radicals, or optionally substituted straight or branched, C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene radicals which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NR A —) link wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl; X 1 represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —C(═O)NR 4 —, —NR 4 C(═O)NR 5 —, —NR 4 S(═O) 2 —, or —S(═O) 2 NR 4 — wherein R 4 and R 5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R 1 R 2 NH—Y-L 1 -X 1 -[CH 2 ] Z — and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONIIOII, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.

  式(I)的化合物是组蛋白去乙酰化酶活性抑制剂，可用于治疗癌症等疾病，其中R1是羧酸基（-COOH）或可由一个或多个细胞内羧酸酯酶水解为羧酸基的酯基；R2是天然或非天然α氨基酸的侧链；Y是键，-C（=O），-S（=O）2-，-C（=O）O-，-C（=O）NR3-，-C（=S）-NR3，-C（=NH）NR3或-S（=O）2NR3-，其中R3是氢或可选取代的C1-C6烷基；L1是式-(Alk1)m(Q)n(Alk2)p-的二价基团，其中m、n和p独立地为0或1，Q是（i）一个可选取代的二价单环或双环碳环或杂环基团，具有5-13个环成员，或（ii）在m和p均为0的情况下，是式-Q1-X2-或-X2-Q1-的二价基团，其中X2是-O-，-S-或-NRA-，其中RA是氢或可选取代的C1-C3烷基，Q1是可选取代的二价单环或双环碳环或杂环基团，具有5-13个环成员，Alk1和Alk2独立地表示可选取代的二价C3-C7环烷基基团，或可选取代的直链或支链，C1-C6烷基，C2-C6烯基或C2-C6炔基基团，其可以可选地含有或终止于醚（-O-），硫醚（-S-）或氨基（-NRA-）链，其中RA是氢或可选取代的C1-C3烷基；X1表示键，-C（=O）或-S（=O）2-；-NR4C（=O）-，-C（=O）NR4-，-NR4C（=O）NR5-，-NR4S（=O）2-或-S（=O）2NR4-，其中R4和R5独立地为氢或可选取代的C1-C6烷基；z为0或1；A表示可选取代的单环、双环或三环碳环或杂环系统，其中基团R1R2NH-Y-L1-X1-[CH2]Z-和HONHCO-[LINKER]-附着在不同的环原子上；-[Linker]-表示将A中的一个环原子与羟酰胺酸基团CONIIOII连接的二价连接基团，连接基团的长度，从连接到A环原子的末端原子到连接到羟酸胺基团的末端原子，相当于从3-10个碳原子的直链饱和碳氢链的长度。
• Enzyme Inhibitors
  申请人：Davidson Alan Hornsby

  公开号：US20090291978A1

  公开（公告）日：2009-11-26

  Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R 1 is a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxyesterase enzymes to a carboxylic acid group; R 2 is the side chain of a natural or non-natural alpha amino acid; Y is a bond, C(═O)—, —S(═O) 2 —, —C(—O)O—, —C(O)NR 3 —, —C(═S)—NR 3 , —C(═NH)NR 3 or —S(═O) 2 NR 3 — wherein R 3 is hydrogen or optionally substituted C 1 -C 6 alkyl; L is a divalent radical of formula -(Alk 1 ) m (O) n (Alk 2 ) p — wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a divalent radical of formula —X 2 -Q 1 - or -Q 1 -X 2 — wherein X 2 is —O—, S— or NR A — wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl, and Q 1 is an optionally substituted divalent mono- or bicyclic carbocyclic or hetero-cyclic radical having 5-13 ring members, AIk 1 and AIk 2 independently represent optionally substituted divalent C 3 -C 7 cycloalkyl radicals, or optionally substituted straight or branched, C 1 -C 6 alkylene, C 2 -C 6 alkenylene, or C 2 -C 6 alkynylene radicals which may optionally contain or terminate in an ether (—O—), thioether (—S—) or amino (—NR A -) link wherein R A is hydrogen or optionally substituted C 1 -C 3 alkyl; X represents a bond; —C(═O); or —S(═O) 2 —; —NR 4 C(═O)—, —C(═O)NR 4 —, —NR 4 C(═O)NR 5 —, —NR 4 S(═O) 2 —, or —S(═O) 2 NR 4 — wherein R 4 and R 5 are independently hydrogen or optionally substituted C 1 -C 6 alkyl; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R 1 R 2 NH—Y-L 1 -X 1 —[CH 2 ] z — and HONHCO-[LINKER]- are attached different ring atoms; and -[Linker]- represents a divalent linker radical linking a ring atom in A with the hydroxamic acid group CONHOH, the length of the linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the hydroxamic acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms.

  式(I)的化合物是组蛋白去乙酰化酶抑制剂，可用于治疗癌症等疾病，其中R1是羧酸基（-COOH）或一个可被一个或多个细胞内羧酸酯酶水解为羧酸基的酯基；R2是天然或非天然α氨基酸的侧链；Y是键，C（═O）—，—S（═O）2—，—C（—O）O—，—C（O）NR3—，—C（═S）—NR3，—C（═NH）NR3或—S（═O）2NR3—，其中R3是氢或可选择性取代的C1-C6烷基；L是式-(Alk1)m(O)n(Alk2)p-的二价基团，其中m、n和p分别独立为0或1；Q是（i）一个可选择性取代的二价单环或双环碳环或杂环基团，其具有5-13个环成员，或（ii）在m和p都为0的情况下，是式—X2-Q1-或-Q1-X2—的二价基团，其中X2是—O—，S—或NRA—，其中RA是氢或可选择性取代的C1-C3烷基，Q1是一个可选择性取代的二价单环或双环碳环或杂环基团，其具有5-13个环成员，Alk1和Alk2独立地表示可选择性取代的二价C3-C7环烷基基团，或可选择性取代的直链或支链C1-C6烷基、C2-C6烯基或C2-C6炔基基团，其可以选择性地包含或终止于醚（-O-）、硫醚（-S-）或氨基（-NRA-）链，其中RA是氢或可选择性取代的C1-C3烷基；X表示键，—C（═O）；或—S（═O）2—；—NR4C（═O）—，—C（═O）NR4—，—NR4C（═O）NR5—，—NR4S（═O）2—或—S（═O）2NR4—，其中R4和R5独立地为氢或可选择性取代的C1-C6烷基；z为0或1；A表示可选择性取代的单环、双环或三环碳环或杂环系统，其中基团R1R2NH—Y-L1-X1—[CH2]z—和HONHCO-[LINKER]-附着于不同的环原子上；-[Linker]-表示连接A中的一个环原子与羟酰胺酸基团CONHOH的二价连接基团，连接基团的长度，从连接到A环原子的末端原子到连接到羟酸胺基团的末端原子，相当于3-10个碳原子的直链饱和烃链的长度。
• Enzyme inhibitors
  申请人：Chroma Therapeutics Ltd.

  公开号：US07939666B2

  公开（公告）日：2011-05-10

  Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers.

  公式（I）的化合物是组蛋白去乙酰化酶活性的抑制剂，并且在治疗癌症等方面非常有用。
• EP2301939A1
  申请人：——

  公开号：EP2301939A1

  公开（公告）日：2011-03-30
• US7939666B2
  申请人：——

  公开号：US7939666B2

  公开（公告）日：2011-05-10