methyl 2-cyano-3-(3-thienyl)propionate | 115787-70-7

• 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: methyl 2-cyano-3-(3-thienyl)propionate
• 英文别名: methyl 2-cyano-3-(thienyl)propionate；methyl 2-cyano-3-(thien-3-yl)-propionate；Methyl 2-cyano-3-thiophen-3-ylpropanoate
• CAS: 115787-70-7
• 化学式: C₉H₉NO₂S
• 分子量: 195.242
• InChiKey: QFNZQTWYLKLEJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  78.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-cyano-3-(3-thienyl)propionate 在 三乙胺 、 sodium hydroxide 、 magnesium chloride 作用下， 以 水 、 乙腈 为溶剂， 反应 4.5h， 生成 2-(2-氨基-5-硝基-6-羰基-1,6-二氢嘧啶-4-YL)-3-(3-噻嗯基)丙腈
  参考文献：
  名称：

  The Chemical Development of CI-972 and CI-1000:  A Continuous Nitration, A MgCl₂/Et₃N-Mediated C-Alkylation of a Chloronitropyrimidine, A Catalytic Protodediazotization of a Diazonium Salt, and an Air Oxidation of an Amine

  摘要：

  Efficient, large-scale processes were developed for the preparation of the potent PNP inhibitors 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride, monohydrate (1) and 2-amino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride, monohydrate (2), We report (1) a safe, continuous nitration process for the preparation of 2-amino-6-chloro-5-nitro-4-pyrimidinol (8a) and its stable diisopropylamine salt (8b), (2) the first MgCl2/ Et3N-mediated C-alkylation of a chloronitropyrimidine, (3) a rare catalytic protodediazotization of the diazonium salt 2-amino-4-oxo-7-thiophen-3-ylmethyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-6-diazonium chloride (14), (4) a single-step process to prepare 2 directly from 2-amino-6-hydroxy-5-nitro-alpha-(3-thienylmethyl)-4-pyrimidineacetonitrile (12) using a sponge nickel-catalyzed reduction, and (5) a method to convert the over-reduction by-product 2,5-diamino-6-(1-aminomethyl-2-thiophen-3-yl-ethyl)-pyrimidin-4-ol (16) into 2 using air oxidation.

  DOI：

  10.1021/op000298d
• 作为产物：
  描述：

  methyl 2-cyano-3-(thienyl)acrylate 在 5%-palladium/activated carbon 、 氢气 作用下， 以 异丙醇 为溶剂， 50.0 ℃ 、446.08 kPa 条件下， 反应 41.0h， 以89%的产率得到methyl 2-cyano-3-(3-thienyl)propionate
  参考文献：
  名称：

  The Chemical Development of CI-972 and CI-1000:  A Continuous Nitration, A MgCl₂/Et₃N-Mediated C-Alkylation of a Chloronitropyrimidine, A Catalytic Protodediazotization of a Diazonium Salt, and an Air Oxidation of an Amine

  摘要：

  Efficient, large-scale processes were developed for the preparation of the potent PNP inhibitors 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride, monohydrate (1) and 2-amino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one hydrochloride, monohydrate (2), We report (1) a safe, continuous nitration process for the preparation of 2-amino-6-chloro-5-nitro-4-pyrimidinol (8a) and its stable diisopropylamine salt (8b), (2) the first MgCl2/ Et3N-mediated C-alkylation of a chloronitropyrimidine, (3) a rare catalytic protodediazotization of the diazonium salt 2-amino-4-oxo-7-thiophen-3-ylmethyl-4,5-dihydro-3H-pyrrolo[3,2-d]pyrimidine-6-diazonium chloride (14), (4) a single-step process to prepare 2 directly from 2-amino-6-hydroxy-5-nitro-alpha-(3-thienylmethyl)-4-pyrimidineacetonitrile (12) using a sponge nickel-catalyzed reduction, and (5) a method to convert the over-reduction by-product 2,5-diamino-6-(1-aminomethyl-2-thiophen-3-yl-ethyl)-pyrimidin-4-ol (16) into 2 using air oxidation.

  DOI：

  10.1021/op000298d

文献信息

• Inhibitors of human purine nucleoside phosphorylase. Synthesis of pyrrolo[3,2-d]pyrimidines, a new class of purine nucleoside phosphorylase inhibitors as potentially T-cell selective immunosuppressive agents. Description of 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d]pyrimidin-4-one (CI-972)
  作者：Jagadish C. Sircar、Catherine R. Kostlan、Richard B. Gilbertsen、Mary K. Bennett、Mi K. Dong、W. J. Cetenko

  DOI：10.1021/jm00087a015

  日期：1992.5

  Purine nucleoside phosphorylase (PNP) is a purine-metabolizing enzyme in the purine cascade and has been a target for drug design for sometime. A series of potent human PNP inhibitors, pyrrolo[3,2-d]pyrimidines (9-deazaguanines), has been synthesized and evaluated in the enzyme assay and in the cell line assay using MOLT-4 (T-cell) and MGL-8 (B-cell) lymphoblasts for selectivity. One of the compounds

  嘌呤核苷磷酸化酶（PNP）是嘌呤级联反应中的嘌呤代谢酶，在一段时间内一直是药物设计的目标。已经合成了一系列有效的人类PNP抑制剂吡咯并[3,2-d]嘧啶（9-脱氮鸟嘌呤），并在酶检测和细胞系检测中使用MOLT-4（T细胞）和MGL- 8（B细胞）淋巴母细胞具有选择性。发现一种化合物2,6-二氨基-3,5-二氢-7-（3-噻吩甲基）-4H-吡咯并[3,2-d]嘧啶-4-酮（11c; CI-972）成为Ki = 0.83 microM的PNP的中度有效，竞争性和可逆抑制剂。还发现它对MOLT-4淋巴母细胞具有选择性的细胞毒性（IC50 = 3.0 microM），但对MGL-8淋巴母细胞没有细胞毒性，并进行了进一步评估。化合物11c（CI-972）正在临床中开发。
• Analogues of pyrrolo[3,2d]pyrimidin-4-ones
  申请人：Warner-Lambert Co.

  公开号：US04923872A1

  公开（公告）日：1990-05-08

  The present invention is novel derivatives of pyrrolo[3,2-d]pyrimidines and pharmaceutical compositions and methods of use therefor. The derivatives are inhibitors of purine nucleoside phosphorylase selectively cytotoxic to T-cells but not to B-cells in the presence of 2'-deoxyguanosine and, therefore, are for use in the treatment of autoimmune diseases, gout, psoriasis or rejection of transplantation.

  本发明涉及新型吡咯[3,2-d]嘧啶衍生物及其制药组合物和使用方法。这些衍生物是嘌呤核苷酸磷酸化酶的抑制剂，在存在2'-去氧鸟苷的情况下，对T细胞具有选择性细胞毒性，而不对B细胞产生细胞毒作用，因此可用于治疗自身免疫性疾病、痛风、牛皮癣或移植排斥反应。
• J. Med. Chem. 1992, 35, 1605-1609
  作者：

  DOI：——

  日期：——
• 9-deazaguanines
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0260491B1

  公开（公告）日：1991-09-11
• US4923872A
  申请人：——

  公开号：US4923872A

  公开（公告）日：1990-05-08