6-methyl-2phenylpyrimidine-4(3H)-thione | 105759-16-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-methyl-2phenylpyrimidine-4(3H)-thione
• 英文别名: 6-Methyl-2-phenylpyrimidine-4-thiol；6-methyl-2-phenyl-1H-pyrimidine-4-thione
• CAS: 105759-16-8
• 化学式: C₁₁H₁₀N₂S
• mdl: MFCD03083916
• 分子量: 202.28
• InChiKey: YYEMKRULYNRIHT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  56.5
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-methyl-2phenylpyrimidine-4(3H)-thione 、 甲基丙烯腈 以 乙二醇二甲醚 为溶剂， 反应 2.0h， 以60%的产率得到2-methyl-2-(6-methyl-2-phenylpyrimidin-4-yl)-3-sulfanylpropanenitrile
  参考文献：
  名称：

  Nishio, Takehiki; Fujisawa, Masaru; Omote, Yoshimori, Journal of the Chemical Society. Perkin transactions I, 1987, p. 2523 - 2530

  摘要：

  DOI：
• 作为产物：
  描述：

  6-甲基-2-苯基嘧啶-4-酮 在 吡啶 、 P₅S₅ 作用下， 反应 1.0h， 以2.5 g的产率得到6-methyl-2phenylpyrimidine-4(3H)-thione
  参考文献：
  名称：

  Heterocyclic Amplifiers of Phleomycin .X. Derivatives of Diazine Mono-Thiol and Di-Thiol

  摘要：

  制备了一系列带有苯基取代基的吡嗪硫醇和嘧啶硫醇，并将其转化为氨基甲酰甲硫基、2-二甲基氨基乙硫基和 2-氨基乙硫基衍生物。吡嗪-2,3-和-2,6-二硫醇的类似衍生物也是与 N,N-二甲基-2-（1′- 和 2′-萘氧基）乙胺一起制备的。作为夫来霉素的放大剂，这些化合物显示出中等的二至三星级活性。

  DOI：

  10.1071/ch9860069

文献信息

• Thiols in Ugi- and Passerini-Smiles-Type Couplings
  作者：Anaëlle Barthelon、Laurent El Kaïm、Marie Gizolme、Laurence Grimaud

  DOI：10.1002/ejoc.200800859

  日期：2008.12

  The use of the Smiles rearrangement in Ugi-type couplings with aromatic mercaptans allows for the straightforward, multicomponent formation of α-arylamino thiocarboxamides. The scope of this new four-component coupling is further broadened with the use of heterocyclic mercapto derivatives that afford thioamides of high biological interest in one step. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim

  在具有芳香族硫醇的Ugi型偶联中使用Smiles重排可以直接，多组分地形成α-芳基氨基硫代羧酰胺。通过使用杂环巯基衍生物可进一步扩大这种新的四组分偶联的范围，该杂环巯基衍生物可在一步之内提供具有高度生物学意义的硫代酰胺。（©Wiley-VCH Verlag GmbH＆Co.KGaA，69451 Weinheim，Germany，2008）
• Dihydropyridine derivatives, processes for their preparation and pharmaceutical compositions thereof
  申请人：FISONS plc

  公开号：EP0225175A2

  公开（公告）日：1987-06-10

  There are described compounds of Formula I, in which R₁, R₂, R₃ and R₄ are as defined in the specification, R₅ is alkyl optionally interrupted by an amide group and optionally substituted by halogen or by a carboxy or a heterocyclic group, X is -O-, -NR-, -S(O)m₁, or a bond, Z is hydrogen or together with R forms a bond, R is hydrogen, alkyl or together with Z forms a bond, R₆ is a 5 or 6 membered unsaturated nitrogen containing heterocyclic ring, optionally fused to a phenyl ring and optionally substituted by one or more of oxo, hydroxy, alkyl, -(CH₂)n₁NH₂, alkoxy, phenyl or -COOH, and when X is -NR- or -S(O)m₁-, R₆ may in addition be hydrogen or a group -CH₂CH₂NH₂, -CH₂CH₂-het. or NHC(=NH)NH₂, when X is -O-, R₆ may also be a group -NH₂, -C(=O) (CH₂)nNH₂, -CH₂CH₂NR₁₄R₁₅ or CH₂CH₂OCH₂CH₂NR₁₄R₁₅, when X is -NR-, -S(O)m₁-, or a bond, R₆ may also be hydrogen or a group -C(=NR₁₂)NHR₁₃, R₁₃ and R₁₄ may be hydrogen or alkyl, R₁₂ is hydrogen, alkylcarbonyl, nitrile or hydroxy, R₁₅ is hydrogen or a group R₁₁, m and m₁ are each 0, 1 or 2, n is 0 or 1, n₁ is an integer from 0 to 6 and pharmaceutically acceptable salts, esters, amides, analogues and protected derivatives thereof.

  所述化合物为式 I、 其中 R₁、R₂、R₃ 和 R₄ 如说明书中所定义、 R₅ 是任选被酰胺基打断并任选被卤素或羧基或杂环基取代的烷基、 X 是-O-、-NR-、-S(O)m₁ 或键、 Z 是氢，或与 R 形成键、 R 是氢、烷基或与 Z 共同形成键、 R₆ 是 5 或 6 个成员的不饱和含氮杂环，可选择与苯基环融合，并可选择被氧 化物、羟基、烷基、-(CH₂)n₁NH₂、烷氧基、苯基或-COOH 中的一个或多个取代、 当 X 为-NR-或-S(O)m₁-时，R₆ 还可以是氢或基团-CH₂CH₂NH₂、-CH₂CH₂-热或 NHC(=NH)NH₂ 、 当 X 为 -O- 时，R₆ 也可以是基团 -NH₂、-C(=O) (CH₂)nNH₂, -CH₂CH₂NR₁₄R₁₅ 或 CH₂CH₂OCH₂CH₂NR₁₄R₁₅、 当 X 为-NR-、-S(O)m₁- 或键时，R₆ 也可以是氢或基团-C(=NR₁₂)NHR₁₃、 R₁₃ 和 R₁₄ 可以是氢或烷基、 R₁₂ 是氢、烷基羰基、腈或羟基、 R₁₅ 是氢或基团 R₁₁、 m 和 m₁ 均为 0、1 或 2、 n 为 0 或 1、 n₁ 是 0 至 6 的整数 及其药学上可接受的盐、酯、酰胺、类似物和受保护的衍生物。
• FIVE- AND SIX-MEMBERED AZA-AROMATIC COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION, AND APPLICATION
  申请人：Xiamen University

  公开号：EP3626718A1

  公开（公告）日：2020-03-25

  The invention relates to the field of medicinal chemistry, and to five-membered-fused-six-membered aza-aromatic ring compound, preparation method thereof, pharmaceutical composition and application thereof. In particular, the invention relates to a type of compounds capable of specifically enhancing ubiquitination degradation of Ras proteins, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with Ras activity in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.

  本发明涉及药物化学领域，涉及五元融合六元杂芳香环化合物、其制备方法、药物组合物及其应用。特别是，本发明涉及一种能够特异性增强 Ras 蛋白泛素化降解的化合物、其制备方法、包含其的药物组合物，以及这些化合物在制造预防或治疗体内 Ras 活性相关疾病的药物中的用途，特别是在制造预防或治疗肿瘤生长和转移的药物中的用途。
• NISHIN, TAKEHIKI;FUJISAWA, MASARU;OMOTE, YOSHIMORI, J. CHEM. SOC. PERKIN TRANS.,(1987) N 11, 2523-2529
  作者：NISHIN, TAKEHIKI、FUJISAWA, MASARU、OMOTE, YOSHIMORI

  DOI：——

  日期：——
• Five-Membered-Fused-Six-Membered Aza-Aromatic Ring Compound, Preparation Method Thereof, Pharmaceutical Composition And Application Thereof
  申请人：XIAMEN UNIVERSITY

  公开号：US20200172521A1

  公开（公告）日：2020-06-04

  The invention relates to the field of medicinal chemistry, and to five-membered-fused-six-membered aza-aromatic ring compound, preparation method thereof, pharmaceutical composition and application thereof. In particular, the invention relates to a type of compounds capable of specifically enhancing ubiquitination degradation of Ras proteins, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with Ras activity in vivo, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis.