2-O-(9H-fluoren-9-ylmethyl) 4-O-methyl (4S)-1,3,4,9-tetrahydropyrido[3,4-b]indole-2,4-dicarboxylate | 914605-06-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-O-(9H-fluoren-9-ylmethyl) 4-O-methyl (4S)-1,3,4,9-tetrahydropyrido[3,4-b]indole-2,4-dicarboxylate
• CAS: 914605-06-4
• 化学式: C₂₈H₂₄N₂O₄
• 分子量: 452.51
• InChiKey: GVBKRUZZANHOFZ-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-O-(9H-fluoren-9-ylmethyl) 4-O-methyl (4S)-1,3,4,9-tetrahydropyrido[3,4-b]indole-2,4-dicarboxylate 在 哌啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (S)-2,3,4,9-tetrahydro-1H-beta-carboline-4-carboxylic acid methyl ester
  参考文献：
  名称：

  WO2006/117549

  摘要：

  公开号：
• 作为产物：
  描述：

  甲醇 、 (R)-2-Fmoc-1,2,3,4-tetrahydronorharmane-3-carboxylic acid 在 三甲基氯硅烷 作用下， 反应 2.0h， 以100%的产率得到2-O-(9H-fluoren-9-ylmethyl) 4-O-methyl (4S)-1,3,4,9-tetrahydropyrido[3,4-b]indole-2,4-dicarboxylate
  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。
• 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
• [EN] ENZYME INHIBITORS<br/>[FR] INHIBITEURS D'ENZYME
  申请人：CHROMA THERAPEUTICS LTD

  公开号：WO2006117549A1

  公开（公告）日：2006-11-09

  [EN] Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R₁ 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; R₂is 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)NR₃-, -C(=S)-NR₃ , -C(=NH)NR₃ or -S(=O)₂NR₃- wherein R₃ is hydrogen or optionally substituted C₁-C₆ alkyl; L¹ is a divalent radical of formula -(Alk¹)_m(Q)_n(Alk²)_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 -X²-Q¹- or -Q¹-X²- wherein X² is -O-, S- or NR^A- wherein R^A is hydrogen or optionally substituted C₁-C₃ alkyl, and Q¹ is an optionally substituted divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5 - 13 ring members, AIk¹ and AIk² independently represent optionally substituted divalent C₃-C₇ cycloalkyl radicals, or optionally substituted straight or branched, C₁-C₆ alkylene, C₂-C₆ alkenylene ,or C₂-C₆ 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 C₁-C₃ alkyl; X¹ represents a bond; -C(=O); or -S(=O)₂-; -NR₄C(=O)-, -C(=O)NR₄-, -NR₄C(=O)NR₅- , -NR₄S(=O)₂-, or -S(=O)₂NR₄-wherein R₄ and R₅ are independently hydrogen or optionally substituted C₁-C₆ alkyl; z is 0 or 1 ; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system wherein the radicals R₁R₂NH-Y-L¹-X¹-[CH₂]_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.
  [FR] Composés de formule (I), inhibiteurs d'histone désacétylase, utiles pour le traitement, par exemple, du cancer. R₁ est un groupe acide carboxylique (-COOH), ou un groupe ester hydrolysable par une ou plusieurs enzymes carboxyestérase intra-cellulaires en groupe acide carboxylique; R₂ est la chaîne latérale d'acide aminé alpha naturel ou non naturel; Y est une liaison, -C(=O)-, -S(=O)₂-, -C(=O)O-, -C(O)NR₃-, -C(=S)-NR₃, -C(=NH)NR₃ ou -S(=O)₂NR₃- sachant que R₃ est hydrogène ou C₁-C₆ alkyle éventuellement substitué; L¹ est un radical divalent de formule -(Alk¹)_m(Q)_n(Alk²)_p- sachant que m, n et p valent indépendamment 0 ou 1, Q est (i) un radical divalent mono- ou bicyclique carbocyclique ou hétérocyclique éventuellement substitué à 5 - 13 chaînons, ou (ii), lorsque m et p valent 0, un radical divalent de formule -X²-Q¹- ou -Q¹-X²- sachant que X² est -O-, S- ou NR^A- et sachant que R^A est hydrogène ou C₁-C₃ alkyle éventuellement substitué, et Q¹ est un radical divalent mono- ou bicyclique carbocyclique ou hétérocyclique éventuellement substitué à 5 - 13 chaînons, AIk¹ et AIk² représentent indépendamment des radicaux C₃-C₇ cycloalkyle divalents éventuellement substitués, ou droits ou ramifiés éventuellement substitués, ou des radicaux C₁-C₆ alkylène, C₂-C₆ alkénylène,ou C₂-C₆ alkynylène qui peuvent éventullement contenir ou avoir en terminaison une liaison éther (-O-), thioéther (-S-) ou amino (-NR^A-) sachant que R^A est hydrogène ou C₁-C₃ alkyle éventuellement substitué; X¹ est une liaison; -C(=O); ou -S(=O)₂-; -NR₄C(=O)-, -C(=O)NR₄-, -NR₄C(=O)NR₅-, -NR₄S(=O)₂-, ou-S(=O)₂NR₄-sachant que R₄ et R₅ sont indépendamment hydrogne ou C₁-C₆ alkyle éventuellement substitué; z vaut 0 ou 1; A est un système de chaîne mono-, bi- or tri-cyclique carbocyclique ou hétérocyclique éventuellement susbstitué sachant que les radicaux R₁R₂NH-Y-L¹-X¹-[CH₂]_Z- et HONHCO-[LINKER]- sont fixés à des atomes cycliques différents; et -[Linker]- est un radical lieur divalent liant entre eux un atome cyclique en A et le groupe acide hydroxamique CONHOH, et que la longueur du radical lieur, depuis l'atome terminal lié à l'atome cyclique en A jusqu'à l'atome terminal lié au groupe acide hydroxamique, équivaut à celle d'une chaîne hydrocarbure saturée non ramifiée comprenant 3-10 atomes de carbone.