7-chloro-5-methyl-2-[(methyloxy)methyl][1,2,4]triazolo[1,5-a]pyrimidine | 121609-00-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 7-chloro-5-methyl-2-[(methyloxy)methyl][1,2,4]triazolo[1,5-a]pyrimidine
• 英文别名: 7-chloro-2-methoxymethyl-5-methyl-s-triazolo[1,5-a]pyrimidine；7-chloro-2-(methoxymethyl)-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidine
• CAS: 121609-00-5
• 化学式: C₈H₉ClN₄O
• 分子量: 212.639
• InChiKey: RPLXWVBVQNGMOB-UHFFFAOYSA-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：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  52.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7-chloro-5-methyl-2-[(methyloxy)methyl][1,2,4]triazolo[1,5-a]pyrimidine 、 五氟化(4-氨苯基)硫 以 乙醇 为溶剂， 以92%的产率得到5-methyl-2-[(methyloxy)methyl]-N-[4-(pentafluoro-λ6-sulfanyl)phenyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine
  参考文献：
  名称：

  Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

  摘要：

  Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmaco-kinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.

  DOI：

  10.1021/jm200592f
• 作为产物：
  描述：

  2,3-Diamino-6-methyl-4(3H)-pyrimidinone 在 三氯氧磷 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 7-chloro-5-methyl-2-[(methyloxy)methyl][1,2,4]triazolo[1,5-a]pyrimidine
  参考文献：
  名称：

  Structure-Guided Lead Optimization of Triazolopyrimidine-Ring Substituents Identifies Potent Plasmodium falciparum Dihydroorotate Dehydrogenase Inhibitors with Clinical Candidate Potential

  摘要：

  Drug therapy is the mainstay of antimalarial therapy, yet current drugs are threatened by the development of resistance. In an effort to identify new potential antimalarials, we have undertaken a lead optimization program around our previously identified triazolopyrimidine-based series of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors. The X-ray structure of PfDHODH was used to inform the medicinal chemistry program allowing the identification of a potent and selective inhibitor (DSM265) that acts through DHODH inhibition to kill both sensitive and drug resistant strains of the parasite. This compound has similar potency to chloroquine in the humanized SCID mouse P. falciparum model, can be synthesized by a simple route, and rodent pharmaco-kinetic studies demonstrated it has excellent oral bioavailability, a long half-life and low clearance. These studies have identified the first candidate in the triazolopyrimidine series to meet previously established progression criteria for efficacy and ADME properties, justifying further development of this compound toward clinical candidate status.

  DOI：

  10.1021/jm200592f

文献信息

• "Triazolo-pyrimidine intermediates"
  申请人：Sankei Pharmaceutical Co., Ltd.

  公开号：US04956462A1

  公开（公告）日：1990-09-11

  There are disclosed a .beta.-lactam compound represented by the formula (I): ##STR1## wherein R.sub.1 represents an acyl group; M represents a hydrogen atom, a protective group of an eliminatable group which is easily hydrolyzable in a human body; B represents a group represented by the formula (b): ##STR2## where at least one of R.sub.2, R.sub.3 and R.sub.9 represent a group represented by the formula: -A-OR.sub.4 where R.sub.4 represents a hydrogen or a lower alkyl group; and A represents a straight or branched alkylene group having 1 to 6 carbon atoms; and a remaining group or groups are each independently a hydrogen atom; a cyano group; a lower alkyl group which may be substituted by a halogen atom; a carbamoyl group which may be substituted by a lower alkyl group; a cycloalkyl group; or a carboxyl group which may be substituted by a protective group of an eliminatable group which is easily hydrolyzable in a human body, and also when R.sub.9 is -A-OR.sub.4, R.sub.2 and R.sub.3 may be combined with each other to form an alkylene group having 3 to 4 carbon atoms; and Z represents a nitrogen atom or a group represented by the formula: C-R.sub.10 where R.sub.10 represents a hydrogen atom, a carboxyl group or a lower alkyl group which may be substituted by a hydroxy group or a lower alkoxy group, or its pharmaceutically acceptable salt, and a process for preparing the same, an intermediate for synthesis of the same and a medicinal composition for bacterially infectious disease therapy containing the same.

  公开了一种β-内酰胺化合物，其表示为公式（I）：##STR1## 其中R.sub.1表示酰基；M表示氢原子，易于水解的可消除基的保护基；B表示由公式（b）表示的基团：##STR2## 其中R.sub.2，R.sub.3和R.sub.9中的至少一个表示由公式-A-OR.sub.4表示的基团，其中R.sub.4表示氢或较低的烷基基团；A表示具有1至6个碳原子的直链或支链烷基基团；其余的基团各自独立地表示氢原子；氰基；可以被卤素原子取代的较低烷基基团；可以被较低烷基基团取代的氨基甲酰基团；环烷基团；或者可以被易于水解的可消除基的保护基取代的羧基团；当R.sub.9为-A-OR.sub.4时，R.sub.2和R.sub.3可以结合形成具有3至4个碳原子的烷基基团；Z表示氮原子或由公式C-R.sub.10表示的基团，其中R.sub.10表示氢原子，羧基或可以被羟基或较低的烷氧基取代的较低烷基基团，或其药学上可接受的盐，以及制备其的方法，用于治疗细菌感染疾病的药用组合物。
• Intermediates for synthesis of cephalosporin compounds
  申请人：Sankei Pharmaceutical Co., Ltd.

  公开号：US04958019A1

  公开（公告）日：1990-09-18

  There are disclosed a .beta.-lactam compound represented by the formula (I): ##STR1## wherein R.sub.1 represents an acyl group; M represents a hydrogen atom, a protective group or an eliminatable group which is easily hydrolyzable in a human body; B represents a group represented by the formula (b): ##STR2## where at least one of R.sub.2, R.sub.3 and R.sub.9 represent a group represented by the formula: --A--OR.sub.4 where R.sub.4 represents a hydrogen or a lower alkyl group; and A represents a straight or branced alkylene group having 1 to 6 carbon atoms; and a remaining group or groups are each independently a hydrogen atom; a cyano group; a lower alkyl group which may be substituted by a halogen atom; a carbamoyl group which may be substituted by a lower alkyl group; a cycloalkyl group; or a carboxyl group which may be substituted by a protective group or an eliminatable group which is easily hydrolyzable in a human body, and also when R.sub.9 is --A--OR.sub.4, R.sub.2 and R.sub.3 may be combined with each other to form an alkylene group having 3 to 4 carbon atoms; and Z represents a nitrogen atom or a group represented by the formula: C--R.sub.10 where R.sub.10 represents a hydrogen atom, a carboxyl group or a lower alkyl group which may be substituted by a hydroxy group or a lower alkoxy group, or its pharmaceutically acceptable salt, and a process for preparing the same, an intermediate for synthesis of the same and a medicinal composition for bacterially infectious disease therapy containing the same.

  公开了一种β-内酰胺化合物，其化学式为(I): ##STR1## 其中R.sub.1代表酰基；M代表氢原子，保护基或易水解的可消除基，在人体中易水解；B代表化学式(b)所代表的基团：##STR2## 其中R.sub.2、R.sub.3和R.sub.9中至少有一个代表化学式--A--OR.sub.4所代表的基团，其中R.sub.4代表氢原子或较低的烷基基团；A代表具有1到6个碳原子的直链或支链烷基基团；其余的基团各自独立地代表氢原子；氰基；可能被卤原子取代的较低烷基基团；可能被较低烷基基团取代的氨基甲酰基基团；环烷基团；或可能被保护基或在人体中易水解的可消除基团取代的羧基基团；当R.sub.9为--A--OR.sub.4时，R.sub.2和R.sub.3可以结合形成具有3到4个碳原子的烷基基团；Z代表氮原子或化学式C--R.sub.10所代表的基团，其中R.sub.10代表氢原子、羧基或可能被羟基或较低的烷氧基取代的较低烷基基团，或其药学上可接受的盐，以及制备它的过程，用于治疗细菌感染疾病的药物组合物。
• Cephalosporin derivatives
  申请人：Sankei Pharmaceutical Co., Ltd.

  公开号：US04987129A1

  公开（公告）日：1991-01-22

  There are disclosed a .beta.-lactam compound represented by the formula (I): ##STR1## wherein R.sub.1 represents an acyl group; M represents a hydrogen atom, a protective group or an eliminatable group which is easily hydrolyzable in a human body; B represents a group represented by the formula (b): ##STR2## where at least one of R.sub.2, R.sub.3 and R.sub.9 represent a group represented by the formula: --A--OR.sub.4 where R.sub.4 represents a hydrogen or a lower alkyl group; and A represents a straight or branched alkylene group having 1 to 6 carbon atoms; and a remaining group or groups are each independently a hydrogen atom; a cyano group; a lower alkyl group which may be substituted by a halogen atom; a carbamoyl group which may be substituted by a lower alkyl group; a cycloalkyl group; or a carboxyl group which may be substituted by a protective group or an eliminatable group which is easily hydrolyzable in a human body, and also when R.sub.9 is --A--OR.sub.4, and R.sub.3 may be combined with each other to form an alkylene group having 3 to 4 carbon atoms; and Z represents a nitrogen atom or a group represented by the formula: C--R.sub.10 where R.sub.10 represents a hydrogen atom, a carboxyl group or a lower alkyl group which may be substituted by a hydroxy group or a lower alkoxy group, or its pharmaceutically acceptable salt, and a process for preparing the same, an intermediate for synthesis of the same and a medicinal composition for bacterially infectious disease therapy containing the same.

  公开了一种β-内酰胺化合物，其表示为式（I）：##STR1##其中，R.sub.1表示酰基；M表示氢原子、保护基或易于在人体内水解的可消除基；B表示由式（b）表示的基团：##STR2##其中，R.sub.2、R.sub.3和R.sub.9中的至少一个表示由式--A--OR.sub.4表示的基团，其中R.sub.4表示氢或较低的烷基基团；A表示具有1到6个碳原子的直链或支链烷基基团；剩余的基团分别独立地表示氢原子、氰基、可以被卤素原子取代的较低烷基基团、可以被较低烷基基团取代的氨基甲酰基团、环烷基团或可以被易于在人体内水解的保护基或可消除基取代的羧基团，当R.sub.9是--A--OR.sub.4时，R.sub.3可以相互结合形成具有3到4个碳原子的烷基基团；Z表示氮原子或由式C--R.sub.10表示的基团，其中R.sub.10表示氢原子、羧基或可以被羟基或较低的烷氧基取代的较低烷基基团，或其药学上可接受的盐，以及制备其的过程、合成其的中间体和用于治疗细菌感染疾病的药物组合物。
• Beta-lactam compound, process for preparing the same, intermediate for synthesis of the same and medicinal composition for bacterially infectious disease therapy containing the same
  申请人：SANKEI PHARMACEUTICAL COMPANY LIMITED

  公开号：EP0302633A2

  公开（公告）日：1989-02-08

  There are disclosed a β-lactam compound represented by the formula (I): wherein R, represents an acyl group; M represents a hydrogen atom, a protective group or an eliminatable group which is easily hydrolyzable in a human body; B represents a group represented by the formula (b): where at least one of R2, R3 and R9 represent a group represented by the formula: -A-OR4 where R4 represents a hydrogen or a lower alkyl group; and A represents a straight or branced alkylene group having 1 to 6 carbon atoms; and a remaining group or groups are each independently a hydrogen atom; a cyano group; a lower alkyl group which may be substituted by a halogen atom; a carbamoyl group which may be substituted by a lower alkyl group; a cycloalkyl group; or a carboxyl group which may be substituted by a protective group or an eliminatable group which is easily hydrolyzable in a human body, and also when Rg is -A-OR4, R2 and R3 may be combined with each other to form an alkylene group having 3 to 4 carbon atoms; and Z represents a nitrogen atom or a group represented by the formula: C-R10 where Rio represents a hydrogen atom, a carboxyl group or a lower alkyl group which may be substituted by a hydroxy group or a lower alkoxy group, or its pharmaceutically acceptable salt, and a process for preparing the same, an intermediate for synthesis of the same and a medicinal composition for bacterially infectious disease therapy containing the same.

  公开了一种由式（I）表示的β-内酰胺化合物： 其中 R 代表酰基；M 代表氢原子、保护基团或在人体内易水解的可消除基团；B 代表由式（b）表示的基团： 其中 R2、R3 和 R9 中至少有一个代表由式表示的基团：-其中 R4 代表氢或低级烷基；A 代表具有 1 至 6 个碳原子的直链或支链亚烷基；其余一个或多个基团各自独立地为氢原子；氰基；可被卤素原子取代的低级烷基；可被低级烷基取代的氨基甲酰基；当 Rg 为-A-OR4 时，R2 和 R3 可相互结合形成具有 3 至 4 个碳原子的亚烷基；Z 代表氮原子或由式表示的基团：C-R10 其中 Rio 代表氢原子、羧基或可被羟基或低级烷氧基取代的低级烷基、 或其药学上可接受的盐，以及制备上述物质、合成上述物质的中间体和含有上述物质的细菌感染性疾病治疗药物组合物的工艺。
• US4956462A
  申请人：——

  公开号：US4956462A

  公开（公告）日：1990-09-11