3-benzyloxycarbonylamino-5-bromo-4-oxopentanoic acid 1,1-dimethylethyl ester | 188890-84-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-benzyloxycarbonylamino-5-bromo-4-oxopentanoic acid 1,1-dimethylethyl ester
• 英文别名: (S)-5-Bromo-4-oxo-3-[[(phenylmethoxy)-carbonyl]amino]-pentanoic acid, 1,1-dimethylethyl ester；3-benzyloxycarbonylamino-5-bromo-4-oxo-pentanoic acid 1,1-dimethylethyl ester；N-benzyloxycarbonyl-3-amino-4-oxo-5-bromopentanoic acid.t-butylester；3-Benzyloxycarbonylamino-5-bromo-4-oxo-pentanoic acid tert-butyl ester；tert-butyl 5-bromo-4-oxo-3-(phenylmethoxycarbonylamino)pentanoate
• CAS: 188890-84-8
• 化学式: C₁₇H₂₂BrNO₅
• 分子量: 400.269
• InChiKey: PBVFTOAYKLEQQO-UHFFFAOYSA-N

物化性质

• 沸点：
  520.2±50.0 °C(Predicted)
• 密度：
  1.346±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-benzyloxycarbonylamino-5-bromo-4-oxopentanoic acid 1,1-dimethylethyl ester 在 palladium on activated charcoal N-甲基吗啉 、 sodium tetrahydroborate 、 氢气 、 sodium hydride 、 戴斯-马丁氧化剂 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 3-[2-[3-(naphthalene-1-carbonylamino)-2-oxopyridin-1-yl]propanoylamino]-4-oxo-5-phenoxypentanoic acid
  参考文献：
  名称：

  PYRIDONE-BASED PEPTIDOMIMETIC INHIBITORS OF INTERLEUKIN-1β-CONVERTING ENZYME (ICE)

  摘要：

  New potent, reversible inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with significantly reduced peptide character are described. The compounds were designed by incorporation of pyridone and pyrimidone heterocyclic replacements for the P-2-P-3 amino acids of the native substrate and were optimised by manipulation of peripheral alkyl and aryl substituents. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00220-5
• 作为产物：
  描述：

  在 氢溴酸 作用下， 以 乙酸乙酯 为溶剂， 生成 3-benzyloxycarbonylamino-5-bromo-4-oxopentanoic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  PYRIDONE-BASED PEPTIDOMIMETIC INHIBITORS OF INTERLEUKIN-1β-CONVERTING ENZYME (ICE)

  摘要：

  New potent, reversible inhibitors of recombinant human Interleukin-1 beta-converting enzyme (ICE, caspase-1) with significantly reduced peptide character are described. The compounds were designed by incorporation of pyridone and pyrimidone heterocyclic replacements for the P-2-P-3 amino acids of the native substrate and were optimised by manipulation of peripheral alkyl and aryl substituents. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00220-5

文献信息

• Tetrazole compound
  申请人：Ono Phramaceutical Co., Ltd.

  公开号：US05710153A1

  公开（公告）日：1998-01-20

  A tetrazole derivatives of formula (I) ##STR1## a non-toxic salt thereof, an acid addition salt thereof or a hydrate thereof which has an inhibitory effect on interleukin-1.beta. converting enzyme (ICE).

  式(I)的四唑衍生物##STR1##及其非毒性盐、酸加盐或水合物，对白细胞介素-1β转化酶（ICE）具有抑制作用。
• [EN] NOVEL INTERLEUKIN-1beta CONVERTING ENZYME INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS D'ENZYMES DE CONVERSION DE L'INTERLEUKINE 1 DOLLAR G(B)
  申请人：PROCTER & GAMBLE

  公开号：WO2003104231A1

  公开（公告）日：2003-12-18

  The present invention relates to novel compounds, compositions comprising said compounds, and uses thereof, said compounds having the formula (a). X is -CH2-, -O- or -NR9-;R is a carbocyclic or heterocyclic ring;R1 is a cysteine trap;R2a, R2a', R2b, and R2b' are each independently hydrogen, C1-C4 alkyl, C1-C4 alkoxy, and mixtures thereof; or R2a' and R2b' can taken together to form a double bond; R9 is hydrogen or a unit having the formula -L2-R10; L is the same as defined herein above; R10 is hydrogen; substituted or unsubstituted C1-C6 linear; branched, or cyclic hydrocarbyl; substituted or unsubstituted aryl; substituted or unsubstituted C1-C9 heterocyclic; and substituted or unsubstituted heteroaryl.

  本发明涉及新化合物、包含所述化合物的组合物以及它们的用途，所述化合物具有以下式（a）。X为-CH2-、-O-或-NR9-；R为碳环或杂环；R1为半胱氨酸陷阱；R2a、R2a'、R2b和R2b'分别独立地为氢、C1-C4烷基、C1-C4烷氧基及它们的混合物；或者R2a'和R2b'可以共同形成双键；R9为氢或具有以下式-L2-R10的单元；L与上文中定义的相同；R10为氢；取代或未取代的C1-C6线性、支链或环烃基；取代或未取代的芳基；取代或未取代的C1-C9杂环基；以及取代或未取代的杂芳基。
• Novel interleukin-1beta converting enzyme inhibitors
  申请人：The Procter & Gamble Company

  公开号：US20030236296A1

  公开（公告）日：2003-12-25

  The present invention relates to interleukin-1&bgr; converting enzyme inhibitors having the formula: 1 R is a carbocyclic or heterocyclic ring; R 1 is a cysteine trap; R 2a , R 2a′ , R 2b , and R 2b are each independently hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, and mixtures thereof; or R 2a′ and R 2b′ can taken together to form a double bond; L and L 1 are linking groups having the formula: 2 T is selected from the group consisting of: i) —NR 6 —; ii) —O—; iii) —NR 6 S(O) 2 —; iv) —S(O) 2 NR 6 —; and v) mixtures thereof; R 6 is hydrogen, substituted or unsubstituted C 1 -C 20 linear, branched, or cyclic alkyl, C 6 -C 20 aryl, C 7 -C 20 alkylenearyl, and mixtures thereof; the indices w, w 1 , and w 2 are each independently 0 or 1; i) hydrogen; ii) C 1 -C 4 linear, branched, and cyclic alkyl; iii) R 3a and R 3b or R 4a , and R 4b can be taken together to form a carbonyl unit; iv) two R 3a or two R 3b units from adjacent carbon atoms or two R 4a or two R 4b units from adjacent carbon atoms can be taken together to form a double bond; and v) mixtures thereof; the index m is from 0 to 5; the index n is from 0 to 5.

  本发明涉及具有以下结构的白细胞介素-1β转化酶抑制剂： 1R为碳环或杂环；R1为半胱氨酸陷阱；R2a、R2a′、R2b和R2b各自独立地为氢、C1-C4烷基、C1-C4烷氧基及其混合物；或R2a′和R2b′可以一起形成双键；L和L1为具有以下结构的连接基： 2T从以下组中选择： i) —NR6—； ii) —O—； iii) —NR6S(O)2—； iv) —S(O)2NR6—；和 v) 其混合物； R6为氢、取代或未取代的C1-C20直链、支链或环烷基、C6-C20芳基、C7-C20烷基芳基及其混合物；指数w、w1和w2各自独立地为0或1； i) 氢； ii) C1-C4直链、支链和环烷基； iii) R3a和R3b或R4a和R4b可以一起形成一个羰基单元； iv) 两个相邻碳原子上的R3a或两个相邻碳原子上的R3b单位，或两个相邻碳原子上的R4a或两个相邻碳原子上的R4b单位可以一起形成双键；和 v) 其混合物； 指数m为0至5；指数n为0至5。
• [EN] 4-OXO-3-(1-OXO-1H-ISOQUINOLIN-2-YLACETYLAMINO)-PENTANOIC ACID ESTER AND AMIDE DERIVATIVES AND THEIR USE AS CASPASE INHIBITORS<br/>[FR] DERIVES D'ESTERS ET D'AMIDES D'ACIDE 4-OXO-3-(1-OXO-1H-ISOQUINOLIN-2-YLACETYLAMINO)-PENTANOIQUE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE CASPASE
  申请人：VERTEX PHARMA

  公开号：WO2004058718A1

  公开（公告）日：2004-07-15

  The present invention provides a compound of formula (I):, wherein: X i s -OR1 or -N (R5) 2 , Y is halo, trifluorophenoxy, or tetrafluorophenoxy; R1 is: C1-6 straight chained or branched alkyl, alkenyl, or alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with optionally substituted aryl, CF3, C1, F, OMe, OEt, OCF3, CN, or NMe2; C1-6 cycloalkyl, wherein 1-2 carbon atoms in the cycloalkyl is optionally replaced with -0- or -NR5-; R2 is C1-6 straight chained or branched alkyl; R3 is hydrogen, halo, OCF3, CN, or CF3; R4 is hydrogen, halo, OCF3, CN, or CF3; and each R5 is independently H, C1-6 straight chained or branched alkyl, aryl, -O-C1-6 straight chained or branched alkyl, or -O-aryl. The present invention also provides pharmaceutical compositions and methods using such compositions for treating a caspase-mediated disease, particularly in the central nervous system.

  本发明提供了一种化合物，其化学式为（I）：其中：X为-OR1或-N（R5）2，Y为卤素，三氟苯氧基或四氟苯氧基；R1为：C1-6直链或支链烷基，烯基或炔基，其中该烷基，烯基或炔基可选择性地与可选择性取代的芳基，CF3，C1，F，OMe，OEt，OCF3，CN或NMe2取代；C1-6环烷基，其中环烷基中的1-2个碳原子可选择性地被-0-或-NR5-取代；R2为C1-6直链或支链烷基；R3为氢，卤素，OCF3，CN或CF3；R4为氢，卤素，OCF3，CN或CF3；每个R5独立地为H，C1-6直链或支链烷基，芳基，-O-C1-6直链或支链烷基，或-O-芳基。本发明还提供了使用这种组合物治疗卡斯帕酶介导的疾病，特别是中枢神经系统疾病的药物组合物和方法。
• [EN] CASPASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE CASPASES ET LEURS UTILISATIONS
  申请人：VERTEX PHARMA

  公开号：WO2004002961A1

  公开（公告）日：2004-01-08

  The present invention relates to compounds of formula (I); useful as inhibitors of caspases. The present invention also provides pharmaceutically acceptable compositions comprising said compounds, processes for preparing the compounds, and methods of using the compounds and compositions in the treatment of various diseases, conditions, or disorders.

  本发明涉及式（I）的化合物；作为caspases的抑制剂。本发明还提供了含有所述化合物的药学上可接受的组合物，制备这些化合物的方法，以及在治疗各种疾病、状况或障碍中使用这些化合物和组合物的方法。