[6-cyano-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinolin-3-yl]carbamic acid benzyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [6-cyano-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinolin-3-yl]carbamic acid benzyl ester
• 英文别名: benzyl N-[6-cyano-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinolin-3-yl]carbamate
• 化学式: C₂₃H₂₃N₅O₂
• 分子量: 401.468
• InChiKey: QOUAYOGJNDDBIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  83.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [6-cyano-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinolin-3-yl]carbamic acid benzyl ester 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以92%的产率得到3-amino-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinoline-6-carbonitrile
  参考文献：
  名称：

  Second Generation Tetrahydroquinoline-Based Protein Farnesyltransferase Inhibitors as Antimalarials

  摘要：

  Substituted tetrahydroquinolines (THQs) have been previously identified as inhibitors of mammalian protein farnesyltransferase (PFT). Previously we showed that blocking PFT in the malaria parasite led to cell death and that THQ-based inhibitors are the most potent among several structural classes of PFT inhibitors (PFTIs). We have prepared 266 THQ-based PFTIs and discovered several compounds that inhibit the malarial enzyme in the sub- to low-nanomolar range and that block the growth of the parasite (P. falciparum) in the lownanomolar ran-e. This body of structure- activity data can be rationalized in most cases by consideration of the X-ray structure of one of the THQs bound to mammalian PFT together with a homology structural model of the malarial enzyme. The results of this study provide the basis for selection of antimalarial PFTIs for further evaluation in preclinical drug discovery assays.

  DOI：

  10.1021/jm0703340
• 作为产物：
  描述：

  1-甲基-1氢-5-醛基-咪唑 、 (6-cyano-1,2,3,4-tetrahydroquinolin-3-yl)-carbamic acid benzyl ester 在 三氟乙酸 、 三乙基硅烷 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 16.0h， 以47%的产率得到[6-cyano-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinolin-3-yl]carbamic acid benzyl ester
  参考文献：
  名称：

  Second Generation Tetrahydroquinoline-Based Protein Farnesyltransferase Inhibitors as Antimalarials

  摘要：

  Substituted tetrahydroquinolines (THQs) have been previously identified as inhibitors of mammalian protein farnesyltransferase (PFT). Previously we showed that blocking PFT in the malaria parasite led to cell death and that THQ-based inhibitors are the most potent among several structural classes of PFT inhibitors (PFTIs). We have prepared 266 THQ-based PFTIs and discovered several compounds that inhibit the malarial enzyme in the sub- to low-nanomolar range and that block the growth of the parasite (P. falciparum) in the lownanomolar ran-e. This body of structure- activity data can be rationalized in most cases by consideration of the X-ray structure of one of the THQs bound to mammalian PFT together with a homology structural model of the malarial enzyme. The results of this study provide the basis for selection of antimalarial PFTIs for further evaluation in preclinical drug discovery assays.

  DOI：

  10.1021/jm0703340

文献信息

• Second Generation Tetrahydroquinoline-Based Protein Farnesyltransferase Inhibitors as Antimalarials
  作者：Pravin Bendale、Srinivas Olepu、Praveen Kumar Suryadevara、Vivek Bulbule、Kasey Rivas、Laxman Nallan、Brian Smart、Kohei Yokoyama、Sudha Ankala、Prakash Rao Pendyala、David Floyd、Louis J. Lombardo、David K. Williams、Frederick S. Buckner、Debopam Chakrabarti、Christophe L. M. J. Verlinde、Wesley C. Van Voorhis、Michael H. Gelb

  DOI：10.1021/jm0703340

  日期：2007.9.1

  Substituted tetrahydroquinolines (THQs) have been previously identified as inhibitors of mammalian protein farnesyltransferase (PFT). Previously we showed that blocking PFT in the malaria parasite led to cell death and that THQ-based inhibitors are the most potent among several structural classes of PFT inhibitors (PFTIs). We have prepared 266 THQ-based PFTIs and discovered several compounds that inhibit the malarial enzyme in the sub- to low-nanomolar range and that block the growth of the parasite (P. falciparum) in the lownanomolar ran-e. This body of structure- activity data can be rationalized in most cases by consideration of the X-ray structure of one of the THQs bound to mammalian PFT together with a homology structural model of the malarial enzyme. The results of this study provide the basis for selection of antimalarial PFTIs for further evaluation in preclinical drug discovery assays.