1-(3,5-dibromophenyl)-2-methylpropan-1-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3,5-dibromophenyl)-2-methylpropan-1-one
• 英文别名: 1-(3,5-Dibromophenyl)-2-methylpropan-1-one
• 化学式: C₁₀H₁₀Br₂O
• 分子量: 305.997
• InChiKey: CWXXCFRUHONPKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-(3,5-dibromophenyl)-2-methylpropan-1-one 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 四氯化钛 、 sodium carbonate 作用下， 以 四氢呋喃 、 氯仿 、 水 、 甲苯 为溶剂， 反应 53.5h， 生成 {1-[3-bromo-5-(5-chlorothien-2-yl)phenyl]-2-methylpropylidene}propanedinitrile
  参考文献：
  名称：

  Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures

  摘要：

  Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development., We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t(1/2) > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 angstrom resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.

  DOI：

  10.1021/acs.jmedchem.7b00008
• 作为产物：
  描述：

  3,5-二溴苯甲酸 在 N,N'-羰基二咪唑 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 反应 19.0h， 生成 1-(3,5-dibromophenyl)-2-methylpropan-1-one
  参考文献：
  名称：

  [EN] SHMT INHIBITORS
  [FR] INHIBITEURS DE LA SHMT

  摘要：

  本发明涉及一种治疗癌症或自身免疫疾病的方法，包括给予丝氨酸羟甲基转移酶（SHMT）抑制剂的治疗，特别是给予如下所述的Formula（VI）的吡唑吡喃化合物的治疗，其中这些化合物能够抑制哺乳动物的SHMT，例如人类SHMTl和/或SHMT2。该治疗方法还包括可选地给予额外药物作为救援疗法以减少毒性，其中该药物可选择自甲酸酯、甲酸盐、叶酸、甲酸酯或亚叶酸。

  公开号：

  WO2016145252A1

文献信息

• [EN] PYRAZOLOPYRANS HAVING HERBICIDAL AND PHARMACEUTICAL PROPERTIES<br/>[FR] PYRAZOLOPYRANES DOTÉS DE PROPRIÉTÉS PHARMACEUTIQUES ET HERBICIDES
  申请人：BASF SE

  公开号：WO2013182472A1

  公开（公告）日：2013-12-12

  The present invention relates to a pyrazolopyran of the general formula I wherein the variables are defined according to the description, including a tautomer, salt, cleavable prodrug, or mixtures thereof, in particular to said pyrazolopyran for use as a medicament and/or an inhibitor of the enzyme serinehydroxymethyltransferase (SHMT). The invention also relates to a process the preparation of a pyrazolopyran of the formula I, to compositions comprising said compound and processes for the preparation of these compositions. Further it relates to use of the pyrazolopyran of formula I as an herbicide as well as to a method of controlling undesired vegetation.

  本发明涉及一种通式I的吡唑吡喃化合物，其中变量根据描述定义，包括互变异构体、盐、可裂解的前药或其混合物，特别是用作药物和/或酶丝氨酸羟甲基转移酶（SHMT）的抑制剂的所述吡唑吡喃化合物。该发明还涉及一种制备通式I的吡唑吡喃化合物的方法，包括含有所述化合物的组合物以及制备这些组合物的方法。此外，本发明还涉及将通式I的吡唑吡喃化合物用作除草剂，以及一种控制不受欢迎植被的方法。
• PYRAZOLOPYRANS HAVING HERBICIDAL AND PHARMACEUTICAL PROPERTIES
  申请人：BASF SE

  公开号：US20150126371A1

  公开（公告）日：2015-05-07

  The present invention relates to a pyrazolopyran of the general formula I wherein the variables are defined according to the description, including a tautomer, salt, cleavable prodrug, or mixtures thereof, in particular to said pyrazolopyran for use as a medicament and/or an inhibitor of the enzyme serinehydroxymethyltransferase (SHMT). The invention also relates to a process the preparation of a pyrazolopyran of the formula I, to compositions comprising said compound and processes for the preparation of these compositions. Further it relates to use of the pyrazolopyran of formula I as an herbicide as well as to a method of controlling undesired vegetation.

  本发明涉及一种通式I的吡唑吡喃化合物，其中变量根据说明定义，包括互变异构体、盐、可裂解的前药或其混合物，特别是用作药物和/或酶丝氨酸羟甲基转移酶（SHMT）的抑制剂的该吡唑吡喃化合物。本发明还涉及一种制备通式I的吡唑吡喃化合物的方法，包括含有该化合物的组合物以及制备这些组合物的方法。此外，本发明还涉及将通式I的吡唑吡喃化合物用作除草剂以及控制不良植被的方法。
• SHMT Inhibitors
  申请人：The Trustees of Princeton University

  公开号：US20180117010A1

  公开（公告）日：2018-05-03

  The present invention relates to a method for the treatment of cancer or an autoimmune disorder, comprising the administration of a serine hydroxymethyltransferase (SHMT) inhibitor, and in particular the administration of pyrazolopyran compounds of Formula (VI) as presently described, wherein the compounds are capable of inhibiting a mammalian SHMT, such as human SHMT1 and/or SHMT2. The treatment method further comprises the optional administration of an additional agent as a rescue therapy to reduce toxicity, wherein said agent may be chosen from formate, a formate salt, folinic acid, formate ester, or leucovorin.
• US9480259B2
  申请人：——

  公开号：US9480259B2

  公开（公告）日：2016-11-01
• Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures
  作者：Geoffrey Schwertz、Matthias C. Witschel、Matthias Rottmann、Roger Bonnert、Ubolsree Leartsakulpanich、Penchit Chitnumsub、Aritsara Jaruwat、Wanwipa Ittarat、Anja Schäfer、Raphael A. Aponte、Susan A. Charman、Karen L. White、Abhijit Kundu、Surajit Sadhukhan、Mel Lloyd、Gail M. Freiberg、Myron Srikumaran、Marc Siggel、Adrian Zwyssig、Pimchai Chaiyen、François Diederich

  DOI：10.1021/acs.jmedchem.7b00008

  日期：2017.6.22

  Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development., We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t(1/2) > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 angstrom resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.