7-(methylthio)-2-tetralone

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 7-(methylthio)-2-tetralone
• 英文别名: 7-methylsulfanyl-3,4-dihydro-1H-naphthalen-2-one
• 化学式: C₁₁H₁₂OS
• 分子量: 192.282
• InChiKey: BOKKLTJGNYYFKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-(methylthio)-2-tetralone 在 sodium ethanolate 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 22.25h， 生成 3-amino-5,6-dihydro-9-(methylthio)benzo[f]quinazolin-1(2H)-one
  参考文献：
  名称：

  Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some 3-amino- and 3-methylbenzo[f]quinazolin-1(2H)-ones

  摘要：

  The synthesis and thymidylate synthase (TS) inhibitory activity of a series of simple benzo-[f]-quinazolin-1(2H)-ones are described. Fully aromatic 3-amino compounds with compact lipophilic substituents in the 9-position were found to have I50 values as low as 20 nM on the isolated enzyme, and represent the first examples of potent, folate-based TS inhibitors that completely lack any structural feature corresponding to the (p-aminobenzoyl)glutamate moiety of the cofactor. A number of the compounds also showed moderate growth inhibitory activity against a human colon adenocarcinoma cell line (SW480), with IC50 values as low as 2 muM.

  DOI：

  10.1021/jm00068a004
• 作为产物：
  描述：

  3-氨基苯乙酸甲酯 在 盐酸 、 sodium hydroxide 、 三氯化铝 、 草酰氯 、 sodium nitrite 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 7-(methylthio)-2-tetralone
  参考文献：
  名称：

  Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some 3-amino- and 3-methylbenzo[f]quinazolin-1(2H)-ones

  摘要：

  The synthesis and thymidylate synthase (TS) inhibitory activity of a series of simple benzo-[f]-quinazolin-1(2H)-ones are described. Fully aromatic 3-amino compounds with compact lipophilic substituents in the 9-position were found to have I50 values as low as 20 nM on the isolated enzyme, and represent the first examples of potent, folate-based TS inhibitors that completely lack any structural feature corresponding to the (p-aminobenzoyl)glutamate moiety of the cofactor. A number of the compounds also showed moderate growth inhibitory activity against a human colon adenocarcinoma cell line (SW480), with IC50 values as low as 2 muM.

  DOI：

  10.1021/jm00068a004

文献信息

• Pharmaceutically active benzoquinazoline compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP1199307B1

  公开（公告）日：2004-02-25
• BICYCLIC AMINE DERIVATIVES AND THEIR USE AS ANTI-PSYCHOTIC AGENTS
  申请人：SMITHKLINE BEECHAM PLC

  公开号：EP0817767A1

  公开（公告）日：1998-01-14
• US6008219A
  申请人：——

  公开号：US6008219A

  公开（公告）日：1999-12-28
• [EN] BICYCLIC AMINE DERIVATIVES AND THEIR USE AS ANTI-PSYCHOTIC AGENTS<br/>[FR] DERIVES AMINES BICYCLIQUES ET LEUR UTILISATION COMME AGENTS NEUROLEPTIQUES
  申请人：SMITHKLINE BEECHAM PLC

  公开号：WO1996030333A1

  公开（公告）日：1996-10-03

  (EN) Compounds of formula (I), wherein X represents a single bond, O, S or CR9R10 where R9 and R10 each independently represent a hydrogen atom or a C1-4alkyl group; R1a, R1b and R1c each independently represent a substituent selected from: a hydrogen or halogen atom, a hydroxy, cyano, trifluoromethyl, trifluoromethoxy, trifluoromethanesulfonyloxy, C1-4alkyl, C1-4alkoxy, C1-4alkylthio, C1-4alkoxyC1-4alkyl, C3-6cycloalkylC1-4alkoxy, C1-4alkanoyl, C1-4alkoxycarbonyl, C1-4alkylsulphonyl, C1-4alkylsulphonyloxy, or C1-4alkylsulphonylC1-4alkyl, arylsulphonylarylsulphonyloxy or arylsulphonylC1-4alkyl group, or a group R11OCO(CH2)p, R11R12NCO(CH2)p or R11R12NSO2(CH2)p where each of R11 and R12 independently represents a hydrogen atom or a C1-4alkyl group and p represents zero or an integer from 1 to 4; R2, R3, R4 and R5 each independently represent a hydrogen atom or a C1-4alkyl group; R6 represents a hydrogen atom or a C1-6alkyl, C3-6alkenyl or arylC1-4alkyl group; R7 represents a hydrogen atom or a C1-4alkyl group; and R8 represents a group of structure (a), (b) or (c) and salts thereof are useful in therapy, as modulators of D3 receptors, in particular as antipsychotic agents.(FR) L'invention concerne des composés de la formule (1). Dans cette formule, X représente une liaison simple, O, S ou CR9R10, où R9 et R10 représentent chacun d'une manière indépendante un atome d'hydrogène ou un groupe C1-4 alkyle; R1a, R1b et R1c représentent chacun d'une manière indépendante un substituant choisi parmi un atome d'hydrogène, ou d'halogène, un groupe hydroxy, cyano, trifluorométhyle, trifluorométhoxy, trifluorométhanesulfonyloxy, C1-4 alkyle, C1-4 alcoxy, C1-4alkylthio, C1-4alcoxyC1-4alkyle, C3-6 cycloalkyl C1-4 alcoxy, C1-4 alcanoyle, C1-4 alcoxycarbonyle, C1-4 alkylsulfonyle, C1-4 alkylsulfonyloxy ou C1-4 alkylsulfonyl C1-4 alkyle, arylsulfonylarylsulfonyloxy ou arylsulfonyl C1-4 alkyle, ou un groupe R11OCO(CH2)p, R11R12NCO(CH2)p ou R11R12NSO2(CH2)p, où chaque R11 et R12 représentent d'une manière indépendante un atome d'hydrogène ou un groupe C1-4 alkyle et p représente 0 ou un nombre entier entre 1 et 4; R2, R3, R4 et R5 représentent d'une manière indépendante un atome d'hydrogène ou un groupe C1-4 alkyle; R6 représente un atome d'hydrogène ou un groupe C1-6 alkyle, un C3-6 alcényle ou un aryl C1-4 alkyle. R7 représente un atome d'hydrogène ou un groupe C1-4 alkyle; enfin, R8 représente un groupe ayant la structure (a), (b), ou (c). L'invention concerne également les sels de ces composés. Ces composés et leurs sels sont utiles en thérapie, comme modulateurs des récepteurs D3 et en particulier comme agents neuroleptiques.
• Benzoquinazoline inhibitors of thymidylate synthase: enzyme inhibitory activity and cytotoxicity of some 3-amino- and 3-methylbenzo[f]quinazolin-1(2H)-ones
  作者：William Pendergast、Jay V. Johnson、Scott H. Dickerson、Inderjit K. Dev、David S. Duch、Robert Ferone、William R. Hall、Joan Humphreys、Joseph M. Kelly、David C. Wilson

  DOI：10.1021/jm00068a004

  日期：1993.8

  The synthesis and thymidylate synthase (TS) inhibitory activity of a series of simple benzo-[f]-quinazolin-1(2H)-ones are described. Fully aromatic 3-amino compounds with compact lipophilic substituents in the 9-position were found to have I50 values as low as 20 nM on the isolated enzyme, and represent the first examples of potent, folate-based TS inhibitors that completely lack any structural feature corresponding to the (p-aminobenzoyl)glutamate moiety of the cofactor. A number of the compounds also showed moderate growth inhibitory activity against a human colon adenocarcinoma cell line (SW480), with IC50 values as low as 2 muM.