3-(2-fluorobenzylamino)-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinoline-6-carbonitrile | 954103-19-6

• 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: 3-(2-fluorobenzylamino)-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinoline-6-carbonitrile
• 英文别名: 3-[(2-fluorophenyl)methylamino]-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinoline-6-carbonitrile
• CAS: 954103-19-6
• 化学式: C₂₂H₂₂FN₅
• 分子量: 375.449
• InChiKey: BTUBHADCOGEENQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  56.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(2-fluorobenzylamino)-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinoline-6-carbonitrile 、 丙基磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-[6-cyano-1-[(3-methylimidazol-4-yl)methyl]-3,4-dihydro-2H-quinolin-3-yl]-N-[(2-fluorophenyl)methyl]propane-1-sulfonamide
  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：

  2-氟溴苄 、 3-amino-1-(3-methyl-3H-imidazol-4-ylmethyl)-1,2,3,4-tetrahydroquinoline-6-carbonitrile 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3-(2-fluorobenzylamino)-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

文献信息

• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT NEUROINFLAMMATORY DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160303146A1

  公开（公告）日：2016-10-20

  This invention provides methods and pharmaceutical compositions that can treat neuroinflammatory disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT AUTOIMMUNE DISORDERS
  申请人：TABACZYNSKI David A.

  公开号：US20160375041A1

  公开（公告）日：2016-12-29

  The invention provides methods and pharmaceutical compositions that can treat autoimmune disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• [EN] INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT AUTOIMMUNE DISORDERS<br/>[FR] INHIBITION DE VOIES DE BIOSYNTHÈSE D'ISOPRÉNOÏDES POUR TRAITER DES TROUBLES AUTO-IMMUNS
  申请人：TABACZYNSKI DAVID A

  公开号：WO2015084721A1

  公开（公告）日：2015-06-11

  The invention provides methods and pharmaceutical compositions that can treat autoimmune disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• [EN] INHIBITION OF ISOPRENOID BIOSYNTHETIC PATHWAYS TO TREAT NEUROINFLAMMATORY DISORDERS<br/>[FR] INHIBITION DE VOIES DE BIOSYNTHÈSE D'ISOPRÉNOÏDES POUR TRAITER DES TROUBLES NEURO-INFLAMMATOIRES
  申请人：TABACZYNSKI DAVID A

  公开号：WO2015089349A1

  公开（公告）日：2015-06-18

  This invention provides methods and pharmaceutical compositions that can treat neuroinflammatory disease by reducing the production of pyrophosphate intermediates produced during the biosynthesis of isoprenoids. The pyrophosphate compounds being inhibited are normally produced through the mevalonate and non-mevalonate pathways of the host vertebrate organisms and their symbiotic and pathogenic microorganisms. The methods involve administering to a patient an inhibitor of the mevalonate-dependent pathway, an inhibitor of the non-mevalonate pathway, or combination of such inhibitors.
• 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.