trans-4-(N-carbobenzyloxy)aminomethyl-1-cyclohexane carbonyl chloride | 27687-13-4

• 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: trans-4-(N-carbobenzyloxy)aminomethyl-1-cyclohexane carbonyl chloride
• 英文别名: trans-4-benzyloxycarbonylaminomethylcyclohexanecarbonyl chloride；trans-4-(N-Benzyloxycarbonyl)-aminomethylcyclohexancarbonsaeure-chlorid
• CAS: 27687-13-4
• 化学式: C₁₆H₂₀ClNO₃
• 分子量: 309.793
• InChiKey: PPSRARCZQBUQCB-MQMHXKEQSA-N

物化性质

• 熔点：
  77-82 °C
• 沸点：
  449.4±28.0 °C(Predicted)
• 密度：
  1.193±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.48
• 重原子数：
  21.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.4
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  trans-4-(N-carbobenzyloxy)aminomethyl-1-cyclohexane carbonyl chloride 在 Pd catalyst 氢气 、 三乙胺 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-{(S)-6-Amino-2-[(4-aminomethyl-cyclohexanecarbonyl)-amino]-hexanoylamino}-benzoic acid butyl ester
  参考文献：
  名称：

  Development of Selective Inhibitors against Plasma Kallikrein.

  摘要：

  特异性血浆激肽释放酶抑制剂被设计并合成，其结构-活性关系得到研究。trans-4-氨基甲基环己烷羰基（Tra）-赖氨酰-4-乙氧基羰基苯胺对血浆激肽释放酶和纤溶酶的IC50值分别为23和210微摩尔，说明该化合物对血浆激肽释放酶具有相当高的特异性。Tra-精氨酰-4-乙氧基羰基苯胺对血浆激肽释放酶和纤溶酶的IC50值分别为16和480微摩尔。Tra-高精氨酰-4-羧基苯胺对血浆激肽释放酶和纤溶酶的IC50值分别为14微摩尔和1毫摩尔。最后，Tra-Arg(Mts)-4-乙酰苯胺（ACA）显示出对血浆激肽释放酶的强效且选择性的抑制活性（血浆激肽释放酶的IC50值为2微摩尔，纤溶酶的IC50值为42微摩尔）。

  DOI：

  10.1248/cpb.39.2930
• 作为产物：
  描述：

  trans-4-{[(phenylmethoxy)carbonylamino]methyl}cyclohexanecarboxylic acid 在 氯化亚砜 作用下， 生成 trans-4-(N-carbobenzyloxy)aminomethyl-1-cyclohexane carbonyl chloride
  参考文献：
  名称：

  Development of Active Center-Directed Inhibitors against Plasmin.

  摘要：

  基于纤溶酶的特定底物结构设计了活性中心导向的纤溶酶抑制剂，并进行了合成。研究了它们对纤溶酶的效应以及结构-抑制活性的关系。Nα-反式-4-氨甲基环己烷羰基赖氨酸4-苯甲酰苯胺（Tra-Lys-BZA）对S-2251和纤维蛋白的IC50值分别为15和6.1μM，而Nα-反式-4-氨甲基环己烷羰基赖氨酸4-苄基哌啶酰胺（Tra-Lys-BPP）则没有显示出任何可检测的抑制活性。此外，研究发现Tra-Lys-4-甲氧羰基苯胺对血浆激肽释放酶的抑制作用比纤溶酶更强。

  DOI：

  10.1248/cpb.39.2340

文献信息

• Synthesis and structure-activity study of protease inhibitors. IV. Amidinonaphthols and related acyl derivatives.
  作者：TAKUO AOYAMA、TOSHIYUKI OKUTOME、TOYOO NAKAYAMA、TAKASHI YAEGASHI、RYOJI MATSUI、SHIGEKI NUNOMURA、MASATERU KURUMI、YOJIRO SAKURAI、SETSURO FUJII

  DOI：10.1248/cpb.33.1458

  日期：——

  Various amidinonaphthols and their acyl derivatives were synthesized and evaluated for inhibitory activities against trypsin, plasmin, kallikrein, thrombin, Clr and Cls, as well as against in vitro complement-mediated hemolysis. 6-Amidino-2-naphthyl 4-guanidinobenzoate (74, FUT-175) was found to have potent inhibitory activities, particularly against trypsin (IC50 : 0.02 μM), Clr (IC50 : 0.1 μM) and Cls (IC50 : 0.02 μM), and to be highly effective in inhibiting the complement-mediated hemolysis (IC50 : 0.03μM). FUT-175, furthermore, showed considerable effectiveness in the systemic Forssman shock reaction, in which involvement of the complement system as the pathogenetic factor is well established.

  合成了多种 amidinonaphthol 及其酰基衍生物，并评估了它们对胰蛋白酶、纤溶酶、激肽释放酶、凝血酶、Clr 和 Cls 以及体外补体介导溶血的抑制活性。发现 6-Amidino-2-萘基 4-胍基苯甲酸酯（74，FUT-175）具有强大的抑制活性，尤其对胰蛋白酶（IC50：0.02 μM）、Clr（IC50：0.1 μM）和 Cls（IC50：0.02 μM），并且在抑制补体介导溶血方面非常有效（IC50：0.03 μM）。此外，FUT-175 在全身性福斯曼休克反应中显示出显著的疗效，该反应中补体系统作为致病因素的作用已被充分证实。
• Indole-3-carbonyl and indole-3-sulfonyl derivatives as platelet
  申请人：Abbott Laboratories

  公开号：US05567711A1

  公开（公告）日：1996-10-22

  The present invention provides compounds of formula ##STR1## and the pharmaceutically acceptable salts thereof which are potent antagonists of PAF and are useful in the treatment of PAF-related disorders including asthma, shock, respiratory distress syndrome, acute inflammation, transplanted organ rejection, gastrointestinal ulceration, allergic skin diseases, delayed cellular immunity, parturition, fetal lung maturation, and cellular differentiation.

  本发明提供公式##STR1##的化合物及其药学上可接受的盐，它们是PAF的有效拮抗剂，可用于治疗与PAF相关的疾病，包括哮喘、休克、呼吸窘迫综合征、急性炎症、移植器官排斥、胃肠溃疡、过敏性皮肤病、迟延性细胞免疫、分娩、胎肺成熟和细胞分化。
• Indole cyclohexyl platelet activating factor antagonists
  申请人：Abbott Laboratories

  公开号：US05643922A1

  公开（公告）日：1997-07-01

  The present invention provides compounds of formula ##STR1## and the pharmaceutically acceptable salts thereof which are potent antagonists of PAF and are useful in the treatment of PAF-related disorders including asthma, rhinitis, shock, respiratory distress syndrome, acute inflammation, transplanted organ rejection, gastrointestinal ulceration, allergic skin diseases, delayed cellular immunity, parturition, fetal lung maturation, and cellular differentiation.

  本发明提供了式子##STR1##的化合物及其药学上可接受的盐，这些化合物是PAF的强效拮抗剂，可用于治疗与PAF相关的疾病，包括哮喘，鼻炎，休克，呼吸窘迫综合症，急性炎症，移植器官排斥，胃肠溃疡，过敏性皮肤病，延迟细胞免疫，分娩，胎肺成熟和细胞分化。
• Lysin derivative and proteinase inhibitor
  申请人：Okamoto, Shosuke

  公开号：EP0183271A2

  公开（公告）日：1986-06-04

  A lysine derivative having the general formula: A-Y-Lys- B (L-form) (A) wherein A represents or wherein X and X' independently represent hydrogen, halogen, alkyl, cycloalkyl, alkoxy, aryloxy, dialkylamino, alkylcarbonyl amino, arylcarbonyl amino, and n, is an integer of 3 to 6, n2 is an integer of 1 to 3, and n3 is an integer of 0 to 3; Y represents S02 or CO; -Lys- represents B represents NR1R2, NZW, or tetrahydroquinolyl, wherein R' and R2 independently represents hydrogen provided that both R' and R2 cannot be hydrogen at the same time; alkyl substituted with carboxyl, alkoxycarbonyl, phenyl, hydroxyphenyl, or benzoyl; cycloalkyl which may be substituted with arylcarbonyl; cycloalkyl-alkyl which may be substituted with carboxyl, arylcarbonyl, or aralkyloxycar- bonyi; phenyl which may be substituted with halogen, nitro, cyano, trifluoromethyl, alkyl, alkoxy, alkoxycarbonyl, alkoxycarbonylalkyl, phenylalkyl which may be further substituted with dialkylamino, alkylcarbonyl, phenylalkenyl which may be further substituted with dialkylamino, phenoxy, pheny-Icarbonyl which may be further substituted with an amino, dialkylamino, alkoxycarbonyl, or nitro group, pyridylmethyl, phenyl hydroxyalkyl, alkylsulfonyl, or alkoxycarbonyl alkylcarbonyl, coumaryl which may be substituted with alkyl; quinolyl; adamantyl; norbornyl; or tetrahydronaphthyl; and W is hydrogen; hydroxyl; carboxyl; aminocarbonyl; alkyl; alkoxy carbonyl; phenyl; phenylalkyl which may be substituted with dialkylamino; or phenylcarbonyl which may be substituted with alkoxycarbonyl; or tetrahydroquinolyl; andor the pharmaceutically acceptable salt thereof. This lysine derivative is effective as a proteinase inhibitor.

  具有以下通式的赖氨酸衍生物A-Y-Lys- B（L-形式） (A) 其中 A 代表 或 其中X和X'独立地代表氢、卤素、烷基、环烷基、烷氧基、芳氧基、二烷基氨基、烷基羰基氨基、芳基羰基氨基，n为3至6的整数，n2为1至3的整数，n3为0至3的整数；Y代表S02或CO；-Lys-代表 B 代表 NR1R2、NZW 或四氢喹啉基，其中 R' 和 R2 独立地代表氢，但 R' 和 R2 不能同时为氢；被羧基、烷氧羰基、苯基、羟基苯基或苯甲酰基取代的烷基；可被芳基羰基取代的环烷基；可被羧基、芳基羰基或芳氧基羰基取代的环烷基-烷基；可被卤素、硝基、氰基、三氟甲基、烷基、烷氧基、烷氧羰基、烷氧羰基烷基、可进一步被二烷基氨基取代的苯基烷基、烷基羰基、可进一步被二烷基氨基取代的苯基烯基取代的苯基、可进一步被氨基、二烷基氨基、烷氧羰基或硝基取代的苯氧基、苯基羰基、吡啶甲基、苯基羟烷基、烷基磺酰基或烷氧羰基烷基羰基、可被烷基取代的香豆素基；喹啉基；金刚烷基；降冰片基；或四氢萘基；以及 W 是氢；羟基；羧基；氨基羰基；烷基；烷氧基羰基；苯基；可被二烷基氨基取代的苯基烷基；或可被烷氧基羰基取代的苯基羰基；或四氢喹啉基；以及或其药学上可接受的盐。这种赖氨酸衍生物是有效的蛋白酶抑制剂。
• Trans-4-amino(alkyl)-1-pyridylcarbamoylcyclohexane compounds and pharmaceutical use thereof
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0370498A2

  公开（公告）日：1990-05-30

  A trans-4-amino(alkyl)-1-pyridylcarbamoylcyclohexane compound of the formula: wherein R¹ and R² are the same or different, and respectively represent hydrogen, C₁₋₁₀ alkyl, C₂₋₅ alkanoyl, formyl, C₁₋₄ alkoxy-carbonyl, amidino, C₃₋₇ cycloalkyl, C₃₋₇ cycloalkyl­carbonyl, phenyl, phenylalkyl, benzoyl, naphthoyl, phenylalkoxy­carbonyl, benzylidene, pyridylcarbonyl, piperidyl, pyrroli­dylidene or piperidylidene which may be optionally substituted on the ring or R¹ and R² together with the adjacent nitrogen atom form 5 to 6-membered cycle which may have oxygen atom, sulfur atom or optionally substituted nitrogen atom in the cycle, or together with the adjacent nitrogen atom form phthalimido, R³ represents hydrogen or C₁₋₄ alkyl, R⁴ represents hydrogen or C₁₋₄ alkyl, R⁵ represents hydrogen, hydroxyl C₁₋₄ alkyl or phenylalkoxy. R⁶ represents hydrogen or C₁₋₄ alkyl, A represents single bond, C₁₋₅ straight chain alkylene, or alkylene which is substituted by C₁₋₄ alkyl, n represents 0 to 1, an optical isomer thereof and a pharmaceutically acceptable acid addition salt thereof. These compounds possess antihypertensive activity, and coronary, cerebral and kidney circulation-improving activities and are useful as antihypertensive agents and agents for prevention and treatment of circulatory diseases.

  一种反式-4-氨基(烷基)-1-吡啶基氨基甲酰基环己烷化合物，其式如下 其中R¹和R²相同或不同，并分别代表氢、C₁₋₁₀烷基、C₂₋₅烷酰基、甲酰基、C₁₋₄烷氧基羰基、脒基、C₃₋₇环烷基、C₃₋₇环烷基羰基、苯基、苯基烷基、苯甲酰基、萘甲酰基、苯基烷氧基羰基、亚苄基、吡啶基羰基、亚哌啶基、吡咯烷基或哌啶基、或 R¹ 和 R² 与邻近的氮原子一起形成 5 至 6 元循环，循环中可能有氧原子、硫原子或任选取代的氮原子、R³ 代表氢或 C₁₋₄ 烷基，R⁴ 代表氢或 C₁₋₄ 烷基，R⁵ 代表氢、羟基 C₁₋₄ 烷基或苯基烷氧基。R⁶ 代表氢或 C₁₋₄ 烷基，A 代表单键、C₁₋₅ 直链亚烷基或被 C₁₋₄ 烷基取代的亚烷基，n 代表 0 至 1、其光学异构体及其药学上可接受的酸加成盐。 这些化合物具有降压活性以及改善冠状动脉、大脑和肾脏循环的活性，可用作降压药以及预防和治疗循环系统疾病的药物。