(2R,5S)-(+)-cis-3,5-Dimethyl-2-(3-pyridyl)thiazolidin-4-one | 119383-00-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (2R,5S)-(+)-cis-3,5-Dimethyl-2-(3-pyridyl)thiazolidin-4-one
• 英文别名: (+)-cis-SM-10661；(2R,5S)-3,5-Dimethyl-2-(pyridin-3-yl)thiazolidin-4-one；(2R,5S)-3,5-dimethyl-2-pyridin-3-yl-1,3-thiazolidin-4-one
• CAS: 119383-00-5
• 化学式: C₁₀H₁₂N₂OS
• 分子量: 208.284
• InChiKey: FZXAQGVGSAANBR-OIBJUYFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  58.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (E)-n-(吡啶-3-基亚甲基)甲胺 、 硫代乳酸 以 四氢呋喃 为溶剂， 反应 12.0h， 生成 (-)-trans-3,5-dimethyl-2-(pyridin-3-yl)-thiazolidin-4-one 、 (2R,5S)-(+)-cis-3,5-Dimethyl-2-(3-pyridyl)thiazolidin-4-one
  参考文献：
  名称：

  Tanabe, Yoo; Yamamoto, Hitomi; Murakami, Masanari, Journal of the Chemical Society. Perkin transactions I, 1995, # 7, p. 935 - 948

  摘要：

  DOI：

文献信息

• Structure-activity relationship of optically active 2-(3-pyridyl)thiazolidin-4-ones as a PAF antagonists
  作者：Y. Tanabe、G. Suzukamo、Y. Komuro、N. Imanishi、S. Morooka、M. Enomoto、A. Kojima、Y. Sanemitsu、M. Mizutani

  DOI：10.1016/s0040-4039(00)92633-9

  日期：1991.1

  Two sets of optically active 5-substituted-2-(3-pyridyl)thiazolidin-4-ones, highly potent and selective antagonists of platelet activating factor (PAF), displayed apparently different anti-PAF activities between their enantiomers, wherein these activities depend markedly on the absolute configuration of the 2-position in the thiazolidin-4-ones.

  两组光学活性5-取代的-2-（3-吡啶基）噻唑烷酮-4-酮是血小板活化因子（PAF）的强效和选择性拮抗剂，它们的对映异构体之间表现出明显不同的抗PAF活性，其中这些活性取决于明显地位于噻唑烷-4-酮中2-位的绝对构型上。
• Direct Enantiomeric Separation of Platelet-activating Factor Receptor Antagonist SM-10661 by Ligand-exchange High-performance Liquid Chromatography with a Copper(II)<i>N,S</i>-Dioctyl-<scp>D</scp>-penicillamine Complex
  作者：Masahiko Okamoto、Youichi Ueda、Ken-ichi Takahashi、Hiroshi Nakazawa、Tadashi Doi

  DOI：10.1271/bbb.59.1740

  日期：1995.1

  The enantiomeric separation of SM-10661, a platelet activating factor receptor antagonist, was investigated by HPLC using ligand-exchange chiral stationary phases. The stereoisomers of SM-10661 could all be separated by ligand-exchange HPLC with a Cu(II) N, S-dioctyl-D-penicillamine complex (Sumichiral OA-5000). The mechanism for the resolution includes the involvement of hydrophobic interactions between SM-10661 and Cu(II) D-penicillamine.

  使用配体交换手性固定相，通过 HPLC 研究血小板活化因子受体拮抗剂 SM-10661 对映体的分离。 SM-10661 的立体异构体均可通过配体交换 HPLC 使用 Cu(II) N,S-二辛基-D-青霉胺复合物 (Sumichiral OA-5000) 进行分离。拆分机制包括 SM-10661 和 Cu(II) D-青霉胺之间的疏水相互作用。
• 2-Pyridyl thiazolidin-4-one derivatives as anti-ulcer agents
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：EP0325496A1

  公开（公告）日：1989-07-26

  A 2-pyridyl-thiazolidin-4-one derivative represented by the formula: wherein Ri and R2 are each a hydrogen atom, a C1-C20 alkyl group, a C2-C2o alkenyl group, a C2-C20 alkynyl group, an aryl group, a C3-C8 cycloalkyl group or an aralkyl group which may have a substituent, Rs is a hydrogen atom, a C1-C20 alkyl group, a C2-C20 alkenyl group, a C2-C2o alkynyl group, a C3-C8 cycloalkyl group or an aralkyl group which may have a substituent, P is a pyridyl group or its N-substituted pyridinium salt which may have a substituent, said substituent being selected from the group consisting of halogen atom, cyano group, hydroxy group, amino group, lower alkyl group, lower alkoxy group, lower alkylamino group, halogenated lower alkyl group, acyl group, acyloxy group, acylthio group, acylamino group, carboxyl group, lower alkoxycarbonyl group, carbamoyl group, lower alkyl substituted carbamoyl group, heterocyclic group, and lower cycloalkyl group, and n represents an integer of 0, 1 or 2, or a pharmaceutically acceptable salt thereof is an anti-ulcer agent effective against stress induced ulcers. Some of these compounds are novel.

  一种2-吡啶基噻唑烷-4-酮衍生物，由式表示： 其中 Ri 和 R2 各为氢原子、C1-C20 烷基、C2-C2o 烯基、C2-C20 炔基、芳基、C3-C8 环烷基或可带有取代基的芳烷基，Rs 为氢原子、C1-C20 烷基、C2-C20 烯基、C2-C2o 炔基、C3-C8 环烷基或可带有取代基的芳烷基、C2-C2o 烷基、C3-C8 环烷基或可带有取代基的芳基，P 是吡啶基或其 N-取代的吡啶鎓盐，可带有取代基，所述取代基可选 自卤素原子组成的组、氰基、羟基、氨基、低级烷基、低级烷氧基、低级烷基氨基、卤代低级烷基、酰基、酰氧基、酰硫基、酰氨基、羧基、低级烷氧基羰基、氨基甲酰基、低级烷基取代的氨基甲酰基、杂环基和低级环烷基，且 n 代表 0、1 或 2 的整数，或其药学上可接受的盐。其中一些化合物是新型的。
• CYP2A6 GENE JUDGMENT METHODS
  申请人：SUMITOMO PHARMACEUTICALS COMPANY, LIMITED

  公开号：EP1182266A1

  公开（公告）日：2002-02-27

  There are provided a method of determining a genotype of CYP2A6 gene on the basis of a difference in gene structures of a wild-type gene of CYP2A6 and at least one kind of mutant-type gene associated with mutation of CYP2A6 gene; the method mentioned above, wherein one kind of mutant-type gene associated with mutation of CYP2A6 gene is used, and the mutant-type gene is conversion-type CYP2A6 gene comprising the nucleotide sequence of SEQ ID NO: 4; the method mentioned above, wherein homozygous deletion and heterozygous deletion of CYP2A6 gene are determined by using at least two kinds of mutant-type genes associated with mutation of CYP2A6 gene; a method of determining a genotype of a CYP gene, characterized by carrying out a method comprising the method mentioned above to determine the genotype of the CYP gene; a diagnostic kit for determining a genotype of CYP2A6 gene, comprising 5'-primer capable of hybridizing to both exon 8 of CYP2A6 gene and exon 8 of CYP2A7 gene, 3'-primer capable of specifically hybridizing to exon 9 of CYP2A6 gene, AccII or an isoschizomer thereof, and Eco81I or an isoschizomer thereof; and the like.

  提供了一种根据CYP2A6野生型基因和至少一种与CYP2A6基因突变相关的突变型基因的基因结构差异来确定CYP2A6基因基因型的方法；上述方法中，使用一种与CYP2A6基因突变相关的突变型基因，该突变型基因为转换型CYP2A6基因，该转换型CYP2A6基因包括SEQ ID NO.4的核苷酸序列；上述方法中，使用至少两种与CYP2A6基因突变相关的突变型基因来确定CYP2A6基因的同型缺失和异型缺失；上述方法中，使用至少两种与CYP2A6基因突变相关的突变型基因来确定CYP2A6基因的同型缺失和异型缺失：4； 上述方法中，通过使用至少两种与 CYP2A6 基因突变相关的突变型基因来确定 CYP2A6 基因的同型缺失和杂合型缺失； 一种确定 CYP 基因基因型的方法，其特征在于实施包括上述方法在内的方法来确定 CYP 基因的基因型；一种确定 CYP2A6 基因基因型的诊断试剂盒，包括能与 CYP2A6 基因第 8 外显子和 CYP2A7 基因第 8 外显子杂交的 5'引物、能与 CYP2A6 基因第 9 外显子特异性杂交的 3'引物、AccII 或其异构体和 Eco81I 或其异构体；以及类似试剂。
• Therapeutic and diagnostic methods dependent on CYP2A enzymes
  申请人：Sellers Moncrieff Edward

  公开号：US20050020641A1

  公开（公告）日：2005-01-27

  A method of regulating the activity of human cytochrome P450 isozyme CYP2A6 to control nicotine metabolism or decrease the production of carcinogens from procarcinogens, such as those present in tobacco smoke, in an individual by selectively inhibiting CYP2A6. Various prophylactic (i.e., prevention and treatment) compositions and methods are also described, including an improved oral nicotine composition and method comprising the use of nicotine together with an inhibitor of the CYP2A6 enzyme. Furthermore, it has been discovered that the presence in an individual of a mutant allele of human cytochrome P450 enzyme CYP2A6 (referred to throughout this specification as “CYP2A6” for brevity) is predictive of an individual who: (1) has a decreased risk of becoming a smoker, (ii) will smoke less if he/she becomes dependent, and/or (iii) may be at relatively lower risk for cancer due to both decreased smoke exposure and decreased CYP2A6-mediated activation of tobacco smoke and other procarcinogenic substrates. This invention provides diagnostic methods for predicting tobacco dependence risk and risk for cancers related to CYP2A6 substrates in an individual by analyzing for the presence of a mutant genotype for human cytochrome P450 enzyme CYP2A6 in an individual, ranging from gene duplication (multiple copies of CYP2A6) to single or even no copies due to null alleles or gene deletion.

  一种调节人类细胞色素 P450 同工酶 CYP2A6 活性的方法，通过选择性抑制 CYP2A6 来控制尼古丁的代谢或减少致癌物质（如烟草烟雾中的致癌物质）在人体内的产生。还描述了各种预防（即预防和治疗）组合物和方法，包括一种改进的口服尼古丁组合物和方法，其中包括尼古丁与 CYP2A6 酶抑制剂一起使用。此外，人们还发现，人细胞色素 P450 酶 CYP2A6（为简洁起见，在本说明书中简称为 "CYP2A6"）的突变等位基因在人体内的存在可预测人的以下情况：(1)成为吸烟者的风险降低，(2)如果成为依赖者，吸烟量会减少，和/或(3)由于烟雾暴露减少和 CYP2A6 介导的烟草烟雾和其他致癌底物活化减少，患癌症的风险可能相对较低。本发明通过分析个体中是否存在人类细胞色素 P450 酶 CYP2A6 的突变基因型，从基因重复（CYP2A6 的多个拷贝）到因空等位基因或基因缺失导致的单拷贝或甚至无拷贝，提供了预测烟草依赖风险和与 CYP2A6 底物相关的癌症风险的诊断方法。