5-溴-4-嘧啶甲醛 | 933746-26-0

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-溴-4-嘧啶甲醛
• 中文别名: 5-溴-4-嘧啶羧醛
• 英文名称: 5-bromopyrimidine-4-carbaldehyde
• CAS: 933746-26-0
• 化学式: C₅H₃BrN₂O
• 分子量: 186.996
• InChiKey: KVIYGKRGFGJVFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933599090

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  5-溴-4-嘧啶甲酸	5-bromopyrimidine-4-carboxylic acid	64224-60-8	C5H3BrN2O2	202.995

反应信息

• 作为反应物：
  描述：

  5-溴-4-嘧啶甲醛 在 正丁基锂 、 三乙胺 、 二异丙胺 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 2-(二环己基膦基)联苯 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 (E)-2-(2-(4-(hydroxy(4-(trifluoromethyl)phenyl)methyl)pyrimidin-5-yl)vinyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Optimization of Potency and Pharmacokinetic Properties of Tetrahydroisoquinoline Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists

  摘要：

  Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel expressed in a subpopulation of sensory neurons in the peripheral nervous system. TRPM8 is the predominant mammalian cold temperature thermosensor and is activated by cold temperatures ranging from 8 to 25 C and cooling compounds such as menthol or icilin. TRPM8 antagonists are being pursued as potential therapeutics for treatment of pain and bladder disorders. This manuscript outlines new developments in the SAR of a lead series of 1,2,3,4-tetrahydroisoquinoline derivatives with emphasis on strategies to improve pharmacokinetic properties and potency. Selected compounds were profiled in two TRPM8 target-specific in vivo coverage models in rats (the icilin-induced wet dog shake model and the cold pressor test). Compound 45 demonstrated robust efficacy in both pharmacodynamic models with ED90 values < 3 mg/kg.

  DOI：

  10.1021/jm401955h
• 作为产物：
  描述：

  5-溴-4-嘧啶甲酸 在 二异丁基氢化铝 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 5-溴-4-嘧啶甲醛
  参考文献：
  名称：

  [EN] 6,7-HETEROCYCLIC FUSED 5H-PYRROLO[1,2-C]IMIDAZOLE DERIVATIVES AND THEIR USE AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) AND/OR TRYPTOPHAN 2,3-DIOXYGENASE (TD02) MODULATORS
  [FR] DÉRIVÉS DE 6,7-(HÉTÉROCYCLE FUSIONNÉ)-5H-PYRROLO[1,2-C]IMIDAZOLE ET LEUR UTILISATION EN TANT QUE MODULATEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE (IDO) ET/OU DE LA TRYPTOPHANE 2,3-DIOXYGÉNASE (TD02)

  摘要：

  该发明涉及具有以下结构的新化合物（I）：其中“A”是一个5或6成员的杂芳基团，未取代或取代为定义在权利要求1中的1、2或3个基团；X是一个键或-(CRA1RB1)n-；Y选自：键，-(CRDRE)m-，-O-，-NRF，-S-，-C(O)-，-C(NRF)-，-C(ORF)Rc-，-C(NRFRG)RC-，-C(O)NRF，-NRFC(O)-，-NRFC(O)NRG-，-NRFSO2NRG-，-SO2-，-SO2NRF-，-NRFSO2-，-OC(O)-和-C(O)O-；Z是一个键或-(CRA2RB2)k-；其中m、n和k分别独立选择自1、2、3和4；R1是H或一个3到16成员的完全饱和、部分不饱和或芳香单、二或三环的基团，可选地可能包括1、2或3个从O、N和S中选择的杂原子，并且未取代或取代为定义在权利要求1中的1到5个取代基；R2选自：H，卤素，C1-4烷基，C1-4卤代烷基，-ORA4和用-ORA4取代的C1-4烷基；R3和R4分别独立选择自：H，卤素，C1-4烷基，C1-4卤代烷基，C3-6环烷基，-ORA4，-NRA5RB4，-CN，-SRAS和用-ORA5取代的C1-4烷基；以及包含这些新化合物的药物组合物。更具体地，该发明涉及作为吲哚胺2,3-二氧化酶（IDO）和/或色氨酸2,3-二氧化酶（TD02）调节剂（例如IDO1和IDO2和/或TD02抑制剂）有用的化合物。

  公开号：

  WO2016059412A1

文献信息

• COMPOUNDS FOR THE TREATMENT OF HIV
  申请人：Bondy Steven S.

  公开号：US20140142085A1

  公开（公告）日：2014-05-22

  The invention provides compounds of formula (I): or a salt thereof as described herein. The invention also provides pharmaceutical compositions comprising a compound of formula (I), processes for preparing compounds of formula (I), intermediates useful for preparing compounds of formula I and therapeutic methods for treating a Retroviridae viral infection including an infection caused by the HIV virus.

  本发明提供了以下式子（I）的化合物或其盐，如本文所述。本发明还提供了包括式子（I）化合物的制药组合物，制备式子（I）化合物的方法，用于制备式子I化合物的中间体以及治疗逆转录病毒感染的治疗方法，包括由HIV病毒引起的感染。
• Optimization of Potency and Pharmacokinetic Properties of Tetrahydroisoquinoline Transient Receptor Potential Melastatin 8 (TRPM8) Antagonists
  作者：Daniel B. Horne、Nuria A. Tamayo、Michael D. Bartberger、Yunxin Bo、Jeffrey Clarine、Carl D. Davis、Vijay K. Gore、Matthew R. Kaller、Sonya G. Lehto、Vu V. Ma、Nobuko Nishimura、Thomas T. Nguyen、Phi Tang、Weiya Wang、Beth D. Youngblood、Maosheng Zhang、Narender R. Gavva、Holger Monenschein、Mark H. Norman

  DOI：10.1021/jm401955h

  日期：2014.4.10

  Transient receptor potential melastatin 8 (TRPM8) is a nonselective cation channel expressed in a subpopulation of sensory neurons in the peripheral nervous system. TRPM8 is the predominant mammalian cold temperature thermosensor and is activated by cold temperatures ranging from 8 to 25 C and cooling compounds such as menthol or icilin. TRPM8 antagonists are being pursued as potential therapeutics for treatment of pain and bladder disorders. This manuscript outlines new developments in the SAR of a lead series of 1,2,3,4-tetrahydroisoquinoline derivatives with emphasis on strategies to improve pharmacokinetic properties and potency. Selected compounds were profiled in two TRPM8 target-specific in vivo coverage models in rats (the icilin-induced wet dog shake model and the cold pressor test). Compound 45 demonstrated robust efficacy in both pharmacodynamic models with ED90 values < 3 mg/kg.
• [EN] 6,7-HETEROCYCLIC FUSED 5H-PYRROLO[1,2-C]IMIDAZOLE DERIVATIVES AND THEIR USE AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) AND/OR TRYPTOPHAN 2,3-DIOXYGENASE (TD02) MODULATORS<br/>[FR] DÉRIVÉS DE 6,7-(HÉTÉROCYCLE FUSIONNÉ)-5H-PYRROLO[1,2-C]IMIDAZOLE ET LEUR UTILISATION EN TANT QUE MODULATEURS DE L'INDOLÉAMINE 2,3-DIOXYGÉNASE (IDO) ET/OU DE LA TRYPTOPHANE 2,3-DIOXYGÉNASE (TD02)
  申请人：REDX PHARMA PLC

  公开号：WO2016059412A1

  公开（公告）日：2016-04-21

  This invention relates to novel compounds of formula (I) wherein 'A' is a 5 or 6 membered heteroaryl group, unsubstituted or substituted with 1, 2 or 3 groups as defined in claim 1; X is a bond or -(CRA1RB1)n-; Y is selected from: a bond, -(CRDRE)m-, -O-, -NRF, -S-, -C(O)-, -C(NRF) -, -C(ORF)Rc-, -C(NRFRG)RC-, -C(O)NRF, -NRFC(O)-, -NRFC(O)NRG-, - NRFSO2NRG-, -SO2-, -SO2NRF-, -NRFSO2-, -OC(O)- and -C(O)O-; Z is a bond or -(CRA2RB2)k-; wherein m, n and k are each independently selected from 1, 2, 3 and 4; R1 is H or a 3 to 16 membered fully saturated, partially unsaturated or aromatic mono-, di- or tri-cyclic moiety, which optionally may include 1, 2 or 3 heteroatoms selected from O, N and S, and which is unsubstituted or substituted with 1 to 5 substituents as defined in claim 1; R2 is selected from: H, halo, C1-4alkyl, C1-4 haloalkyl, -ORA4 and C1-4alkyl substituted with -ORA4; and R3 and R4 are each independently selected from: H, halo, C1-4alkyl, C1-4haloalkyl, C3-6cycloalkyl, -ORA4, -NRA5RB4, -CN, -SRAS and C1-4alkyl substituted with -ORA5; and pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as indoleamine 2,3-dioxygenase (IDO) and/or tryptophan 2,3- dioxygenase (TD02) modulators (e.g. IDOl, and ID02 and/or TD02 inhibitors).

  该发明涉及具有以下结构的新化合物（I）：其中“A”是一个5或6成员的杂芳基团，未取代或取代为定义在权利要求1中的1、2或3个基团；X是一个键或-(CRA1RB1)n-；Y选自：键，-(CRDRE)m-，-O-，-NRF，-S-，-C(O)-，-C(NRF)-，-C(ORF)Rc-，-C(NRFRG)RC-，-C(O)NRF，-NRFC(O)-，-NRFC(O)NRG-，-NRFSO2NRG-，-SO2-，-SO2NRF-，-NRFSO2-，-OC(O)-和-C(O)O-；Z是一个键或-(CRA2RB2)k-；其中m、n和k分别独立选择自1、2、3和4；R1是H或一个3到16成员的完全饱和、部分不饱和或芳香单、二或三环的基团，可选地可能包括1、2或3个从O、N和S中选择的杂原子，并且未取代或取代为定义在权利要求1中的1到5个取代基；R2选自：H，卤素，C1-4烷基，C1-4卤代烷基，-ORA4和用-ORA4取代的C1-4烷基；R3和R4分别独立选择自：H，卤素，C1-4烷基，C1-4卤代烷基，C3-6环烷基，-ORA4，-NRA5RB4，-CN，-SRAS和用-ORA5取代的C1-4烷基；以及包含这些新化合物的药物组合物。更具体地，该发明涉及作为吲哚胺2,3-二氧化酶（IDO）和/或色氨酸2,3-二氧化酶（TD02）调节剂（例如IDO1和IDO2和/或TD02抑制剂）有用的化合物。