rac-α-(acetylthiomethyl)-6-phenylhexanoic acid | 116112-45-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: rac-α-(acetylthiomethyl)-6-phenylhexanoic acid
• 英文别名: 2-Acetylthiomethyl-6-phenylhexanoic acid；2-(Acetylsulfanylmethyl)-6-phenylhexanoic acid
• CAS: 116112-45-9
• 化学式: C₁₅H₂₀O₃S
• 分子量: 280.388
• InChiKey: HADJKBMQSUOFEF-UHFFFAOYSA-N

物化性质

• 沸点：
  448.9±45.0 °C(Predicted)
• 密度：
  1.149±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  79.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  rac-α-(acetylthiomethyl)-6-phenylhexanoic acid 以40%的产率得到N-(2'-Acetylthiomethyl-6'-phenylhexanoyl)-D-phenylglycine
  参考文献：
  名称：

  .beta.-thiopropionyl-aminoacid derivatives and their use as

  摘要：

  一种治疗人类或动物细菌感染的方法，包括与β-内酰胺类抗生素联合给药，给予公式(I)的氨基酸衍生物的治疗有效量或其药用可接受的盐、溶剂化合物或体内可水解酯的治疗有效量，其中：R为氢、形成盐的阳离子或体内可水解酯形成基团；R.sub.1为氢、(C.sub.1-6)烷基，可选地被高达三个卤素原子或巯基、(C.sub.1-6)烷氧基、羟基、氨基、硝基、羧基、(C.sub.1-6)烷基羰氧基、(C.sub.1-6)烷氧羰基、甲酰基或(C.sub.1-6)烷基羰基取代，(C.sub.3-7)环烷基，(C.sub.3-7)环烷基(C.sub.2-6)烷基，(C.sub.2-6)烯基，(C.sub.2-6)炔基，芳基，芳基(C.sub.1-6)烷基，杂环烷基或杂环烷基(C.sub.1-6)烷基；R.sub.2为氢，(C.sub.1-6)烷基或芳基(C.sub.1-6)烷基；R.sub.3为氢，(C.sub.1-6)烷基，可选地被高达三个卤素原子取代，(C.sub.3-7)环烷基，融合的芳基(C.sub.3-7)环烷基，(C.sub.3-7)环烷基(C.sub.2-6)烷基，(C.sub.2-6)烯基，(C.sub.2-6)炔基，芳基，芳基-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n，杂环烷基或杂环烷基-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n，其中m为0至3，n为1至3，每个R.sub.10和R.sub.11独立地为氢或(C.sub.1-4)烷基，X为O，S(O).sub.x，其中x为0-2，或键；R.sub.4为氢，或体内可水解的酰基；R.sub.5和R.sub.6独立地为氢和(C.sub.1-6)烷基，或一起代表(CH.sub.2).sub.p，其中p为2至5。一些化合物本身被要求。

  公开号：

  US06048852A1
• 作为产物：
  描述：

  4-苯基-1-丁基溴 在 氢氧化钾 、 二乙胺盐酸盐 、 sodium ethanolate 作用下， 以 乙醇 、 水 、 苯 为溶剂， 反应 34.0h， 生成 rac-α-(acetylthiomethyl)-6-phenylhexanoic acid
  参考文献：
  名称：

  Cysteine Derivatives as Inhibitors for Carboxypeptidase A:  Synthesis and Structure−Activity Relationships

  摘要：

  A series of cysteine (Cys) derivatives having an alkyl or arylalkyl moiety on the a-amino group of the amino acid have been synthesized as a novel type of inhibitor for carboxypeptidase A. These compounds are readily prepared starting with Cys in an optically active form. The structure-activity relationship study revealed that the inhibitors prepared from D-Cys are much more potent than the corresponding inhibitors obtained from L-CYS, and the most potent inhibitor in the series, (S)-1j with a K-i value of 55 +/- 4 nM, is obtained by introducing a phenethyl moiety on the amino group Of D-CyS. In comparison, the most active inhibitor in the series of 2-substituted 3-mercaptopropanoic acid is found to be 20, in which the phenyl ring is linked to the mercaptocarboxylic acid at the a-position with a methylene unit. A proposal that accounts for the different structural requirement for the maximum activity between the two series of inhibitors is provided.

  DOI：

  10.1021/jm010272s

文献信息

• Metallo-β-lactamase inhibitors by bioisosteric replacement: Preparation, activity and binding
  作者：Susann Skagseth、Sundus Akhter、Marianne H. Paulsen、Zeeshan Muhammad、Silje Lauksund、Ørjan Samuelsen、Hanna-Kirsti S. Leiros、Annette Bayer

  DOI：10.1016/j.ejmech.2017.04.035

  日期：2017.7

  High-resolution crystal structures of three inhibitors in complex with VIM-2 revealed hydrophobic interactions for the diethyl groups in the phosphonate ester (inhibitor 2b), the mercapto bridging the two active site zinc ions, and tight stacking of the benzene ring to the inhibitor between Phe62, Tyr67, Arg228 and His263. The inhibitors show reduced enzyme activity in Escherichia coli cells harboring MBL

  细菌耐药性正在削弱β-内酰胺类抗生素（包括碳青霉烯类）的使用。对β-内酰胺的主要抗性机制是丝氨酸或金属-β-内酰胺酶（MBL）介导的β-内酰胺环的水解。尽管已经报道了几种MBLs抑制剂，但没有一种被开发为临床上有用的抑制剂。巯基羧酸是作为MBL抑制剂报道的最突出的支架之一。在这项研究中，巯基羧酸的羧基被生物等位基团所取代，如膦酸酯，膦酸和NH-四唑。评估了置换对生物活性和抑制剂结合的影响。合成了一系列先前报道的抑制剂的生物等排体，并针对MBL VIM-2，NDM-1和GIM-1进行了评估。活性最高的抑制剂将巯基和膦酸酯或酸结合，并有两个/三个碳链连接苯基。令人惊讶地，还含有硫代乙酸酯基团而不是硫醇的化合物也显示出低的IC 50值。与VIM-2配合使用的三种抑制剂的高分辨率晶体结构显示了膦酸酯中的二乙基的疏水相互作用（抑制剂2b），将两个活性位点锌离子桥接的巯基以及苯环紧密堆积在抑制剂上在P
• BETA-THIOPROPIONYL-AMINOACID DERIVATIVES AND THEIR USE AS BETA-LACTAMASE INHIBITORS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0900197A1

  公开（公告）日：1999-03-10
• US6048852A
  申请人：——

  公开号：US6048852A

  公开（公告）日：2000-04-11
• [EN] BETA-THIOPROPIONYL-AMINOACID DERIVATIVES AND THEIR USE AS BETA-LACTAMASE INHIBITORS<br/>[FR] DERIVES D'ACIDES BETA-THIOPROPIONYLE AMINES ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE BETA-LACTAMASE
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1997030027A1

  公开（公告）日：1997-08-21

  (EN) A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a $g(b)-lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or $i(in vivo) hydrolysable ester thereof, wherein: R is hydrogen, a salt forming cation or an $i(in vivo) hydrolysable ester-forming group; R1 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C1-6)alkylcarbonyloxy, (C1-6)alkoxycarbonyl, formyl or (C1-6)alkylcarbonyl group, (C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl(C1-6)alkyl, heterocyclyl or heterocyclyl(C1-6)alkyl; R2 is hydrogen, (C1-6)alkyl or aryl(C1-6)alkyl; R3 is hydrogen, (C1-6)alkyl optionally substituted by up to three halogen atoms, (C3-7)cycloalkyl, fused aryl(C3-7)cycloalkyl, (C3-7)cycloalkyl(C2-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl-(CHR10)m-X-(CHR11)n, heterocyclyl or heterocyclyl-(CHR10)m-X-(CHR11)n, where m is 0 to 3, n is 1 to 3, each R10 and R11 is independently hydrogen or (C1-4)alkyl and X is O, S(O)x where x is 0-2, or a bond; R4 is hydrogen, or an $i(in vivo) hydrolysable acyl group; and R5 and R6 are independently hydrogen and (C1-6)alkyl or together represent (CH2)p where p is 2 to 5. Some compounds are claimed per se.(FR) Procédé de traitement d'infections bactériennes chez l'homme ou chez l'animal, consistant à administrer, combiné à un antibiotique de $g(b)-lactame, une quantité efficace sur le plan thérapeutique d'un dérivé d'acide aminé de Formule (I) ou d'un de ses sels, solvates ou esters hydrolysables $i(in vivo), acceptables sur le plan pharmaceutique, formule dans laquelle R représente hydrogène, un cation formant un sel ou un groupe formant un ester hydrolysable in vivo; R1 représente hydrogène, alkyle C1-C6 éventuellement substitué par trois atomes d'halogène au maximum ou par un groupe mercapto, alcoxy C1-C6,hydroxy, amino, nitro, carboxy, alkylcarbonyloxy C1-C6, alcoxycarbonyle C1-C6, formyle ou alkylcarbonyle C1-C6, cycloalkyle C3-C7, cycloalkyle C3-C7 alkyle C2-C6, alkényle C2-C6, alkynyle C2-C6, aryle, arylalkyle C1-C6, hétérocyclyle ou hétérocyclyle alkyle C1-C6; R2 représente hydrogène, alkyle C1-C6 ou aryle alkyle C1-C6; R3 représente hydrogène, alkyle C1-C6 éventuellement substitué par trois atomes d'halogène au maximum, cycloalkyle C3-C7, aryl fusionné cycoalkyle C3-C7, cycloalkyle C3-C7 alkyle C2-C6, alkényle C2-C6, alkynyle C2-C6, aryle-(CHR10)m-X-(CHR11)n, hétérocyclyle ou hétérocyclyle-(CHR10)m-X (CHR11)n dans laquelle m est 0 à 3, n est 1 à 3, chaque R10 et R11 représente indépendamment hydrogène ou alkyle C1-C4 et X représente 0-2 ou une liaison; R4 représente hydrogène ou un groupe acyle hydrolysable $i(in vivo); R5 et R6 représentent indépendamment hydrogène et alkyle C1-C6 ou représentent ensemble (CH2)n dans laquelle p est 2 à 5. On revendique certains composés.
• .beta.-thiopropionyl-aminoacid derivatives and their use as
  申请人：SmithKline Beecham p.l.c.

  公开号：US06048852A1

  公开（公告）日：2000-04-11

  A method of treatment of bacterial infections in humans or animals which comprises administering, in combination with a .beta.-lactam antibiotic, a therapeutically effective amount of an amino acid derivative of Formula (I) or a pharmaceutically acceptable salt, solvate or in vivo hydrolysable ester thereof, ##STR1## wherein: R is hydrogen, a salt forming cation or an in vivo hydrolysable ester-forming group; R.sub.1 is hydrogen, (C.sub.1-6)alkyl optionally substituted by up to three halogen atoms or by a mercapto, (C.sub.1-6)alkoxy, hydroxy, amino, nitro, carboxy, (C.sub.1-6)alkylcarbonyloxy, (C.sub.1-6)alkoxycarbonyl, formyl or (C.sub.1-6)alkylcarbonyl group, (C.sub.3-7)cycloalkyl, (C.sub.3-7)cycloalkyl(C.sub.2-6)alkyl, (C.sub.2-6)alkenyl, (C.sub.2-6)alkynyl, aryl, aryl(C.sub.1-6)alkyl, heterocyclyl or heterocyclyl(C.sub.1-6)alkyl; R.sub.2 is hydrogen, (C.sub.1-6)alkyl or aryl(C.sub.1-6)alkyl; R.sub.3 is hydrogen, (C.sub.1-6)alkyl optionally substituted by up to three halogen atoms, (C.sub.3-7)cycloalkyl, fused aryl(C.sub.3-7)cycloalkyl, (C.sub.3-7)cycloalkyl(C.sub.2-6)alkyl, (C.sub.2-6)alkenyl, (C.sub.2-6)alkynyl, aryl, aryl-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n, heterocyclyl or heterocyclyl-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n, where m is 0 to 3, n is 1 to 3, each R.sub.10 and R.sub.11 is independently hydrogen or (C.sub.1-4)alkyl and X is O, S(O).sub.x where x is 0-2, or a bond; R.sub.4 is hydrogen, or an in vivo hydrolysable acyl group; and R.sub.5 and R.sub.6 are independently hydrogen and (C.sub.1-6)alkyl or together represent (CH.sub.2).sub.p where p is 2 to 5. Some compounds are claimed per se.

  一种治疗人类或动物细菌感染的方法，包括与β-内酰胺类抗生素联合给药，给予公式(I)的氨基酸衍生物的治疗有效量或其药用可接受的盐、溶剂化合物或体内可水解酯的治疗有效量，其中：R为氢、形成盐的阳离子或体内可水解酯形成基团；R.sub.1为氢、(C.sub.1-6)烷基，可选地被高达三个卤素原子或巯基、(C.sub.1-6)烷氧基、羟基、氨基、硝基、羧基、(C.sub.1-6)烷基羰氧基、(C.sub.1-6)烷氧羰基、甲酰基或(C.sub.1-6)烷基羰基取代，(C.sub.3-7)环烷基，(C.sub.3-7)环烷基(C.sub.2-6)烷基，(C.sub.2-6)烯基，(C.sub.2-6)炔基，芳基，芳基(C.sub.1-6)烷基，杂环烷基或杂环烷基(C.sub.1-6)烷基；R.sub.2为氢，(C.sub.1-6)烷基或芳基(C.sub.1-6)烷基；R.sub.3为氢，(C.sub.1-6)烷基，可选地被高达三个卤素原子取代，(C.sub.3-7)环烷基，融合的芳基(C.sub.3-7)环烷基，(C.sub.3-7)环烷基(C.sub.2-6)烷基，(C.sub.2-6)烯基，(C.sub.2-6)炔基，芳基，芳基-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n，杂环烷基或杂环烷基-(CHR.sub.10).sub.m --X--(CHR.sub.11).sub.n，其中m为0至3，n为1至3，每个R.sub.10和R.sub.11独立地为氢或(C.sub.1-4)烷基，X为O，S(O).sub.x，其中x为0-2，或键；R.sub.4为氢，或体内可水解的酰基；R.sub.5和R.sub.6独立地为氢和(C.sub.1-6)烷基，或一起代表(CH.sub.2).sub.p，其中p为2至5。一些化合物本身被要求。