2-Bromo-5-(4-fluorophenylmethyl)thiophene | 154355-83-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-Bromo-5-(4-fluorophenylmethyl)thiophene
• 英文别名: 2-bromo-<5-(4-fluorophenyl)methyl>thiophene；2-bromo-5-(4-fluorobenzyl)thiophene；2-bromo-5-[(4-fluorophenyl)methyl]thiophene
• CAS: 154355-83-6
• 化学式: C₁₁H₈BrFS
• 分子量: 271.153
• InChiKey: PMLOYQTXZRLCIM-UHFFFAOYSA-N

物化性质

• 沸点：
  316.0±32.0 °C(Predicted)
• 密度：
  1.517±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  28.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-Bromo-5-(4-fluorophenylmethyl)thiophene 以33%的产率得到N-{3-[5-(4-fluorophenylmethyl)-thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea
  参考文献：
  名称：

  [(Substituted) phenyalkyl]furylalkynyl-and [substituted) phenyalkyl]

  摘要：

  本发明涉及以下式的化合物##STR1##及其药用可接受的盐，其中Z选自可选择的取代苯基、呋喃基、噻吩基或噻唑基；该化合物抑制白三烯生物合成，在治疗炎症性疾病状态中有用；还公开了抑制白三烯生物合成的组合物和抑制5-脂氧合酶活性和白三烯生物合成的方法。

  公开号：

  US05288751A1
• 作为产物：
  描述：

  2-(4-氟苄基)噻吩 在 N-溴代丁二酰亚胺(NBS) 、 溶剂黄146 作用下， 以 氯仿 为溶剂， 反应 0.5h， 以98%的产率得到2-Bromo-5-(4-fluorophenylmethyl)thiophene
  参考文献：
  名称：

  Preparation of (R)-(+)-N-[3-[5-[(4-Fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor.

  摘要：

  Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connnecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5-lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N-hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)2-furyl]-1-methyl-2-propynyl]-N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene-mediated disorders.

  DOI：

  10.1021/jm00024a004

文献信息

• [EN] INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION<br/>[FR] INHIBITEURS DE LA RÉPLICATION DU VIRUS DE L'IMMUNODÉFICIENCE HUMAINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014164467A1

  公开（公告）日：2014-10-09

  The disclosure generally relates to compounds of formula I, including compositions and methods for treating human immunodeficiency virus (HIV) infection. The disclosure provides novel inhibitors of HIV, pharmaceutical compositions containing such compounds, and methods for using these compounds in the treatment of HIV infection.

  该披露通常涉及到I式化合物，包括用于治疗人类免疫缺陷病毒（HIV）感染的组合物和方法。该披露提供了HIV的新型抑制剂，含有这些化合物的药物组合物，以及在治疗HIV感染中使用这些化合物的方法。
• [(Substituted) phenyalkyl]furylalkynyl-and [substituted) phenyalkyl]
  申请人：Abbott Laboratories

  公开号：US05288751A1

  公开（公告）日：1994-02-22

  The present invention relates to compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein Z is selected from optionally substituted phenyl, furyl, thienyl or thiazolyl; which inhibits leukotriene biosynthesis and is useful in the treatment of inflammatory disease states; also disclosed are leukotriene biosynthesis inhibiting compositions and a method for inhibiting 5-lipoxygenase activity and leukotriene biosynthesis.

  本发明涉及以下式的化合物##STR1##及其药用可接受的盐，其中Z选自可选择的取代苯基、呋喃基、噻吩基或噻唑基；该化合物抑制白三烯生物合成，在治疗炎症性疾病状态中有用；还公开了抑制白三烯生物合成的组合物和抑制5-脂氧合酶活性和白三烯生物合成的方法。
• Substituted arylalkynyl-and heteroarylalkynl-N-hydroxyurea inhibitors of
  申请人：Abbott Laboratories

  公开号：US05616596A1

  公开（公告）日：1997-04-01

  The invention relates to compounds having activity to inhibit lipoxygenase enzyme activity, to pharmaceutical compositions comprising these compounds, and to a medical method of treating. More particularly, this invention concerns certain substituted arylalkynyl- and ((heteroaryl)alkynyl)-N-hydroxy-ureas which inhibit leukotriene biosynthesis, to pharmaceutical compositions of these compounds and to a method of inhibiting leukotriene biosynthesis.

  该发明涉及具有抑制脂氧酶酶活性的化合物，包括这些化合物的药物组合物，以及治疗的医学方法。更具体地说，这项发明涉及特定的取代芳基炔基和((杂环)炔基)-N-羟基脲，这些化合物抑制白三烯生物合成，以及这些化合物的药物组合物和抑制白三烯生物合成的方法。
• [EN] 7-HETEROARYLSULFONYL-TETRAHYDRO-3-BENZAZEPINE DERIVATIVES AS ANTIPSYCHOTIC AGENTS<br/>[FR] DERIVES DE 7-HETEROARYLSULFONYL-TETRAHYDRO-3-BENZAZEPINE EN TANT QU'AGENTS ANTIPSYCHOTIQUES
  申请人：GLAXO GROUP LTD

  公开号：WO2005025576A1

  公开（公告）日：2005-03-24

  The invention provides compounds of formula (I): wherein A and B represent the groups -(CH2)m- and -(CH2)n- respectively; R1 represents hydrogen or C1-6alkyl; R2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC1-6alkyl, trifluoromethyl, trifluoromethoxy, C1-6alkyl, C1-6alkoxy, C1-6fluoroalkoxy, -(CH2)pC3-6cycloalkyl, -(CH2)pOC3-6cycloalkyl, -COC1-6alkyl, -SO2 C1-6alkyl, -SOC1-6alkyl, -S-C1-6alkyl, -CO2C1-6alkyl, -CO2NR3R4, -SO2NR3R4, -(CH2)pNR3R4, -(CH2)pNR3COR4, optionally substituted aryl ring, optionally substituted heteroaryl ring, a fused bicyclic heteroaromatic ring system or optionally substituted heterocyclyl ring; Ar1 represents optionally substituted heteroaryl ring; Ar2 represents optionally substituted aryl ring or optionally substituted heteroaryl ring; Z represents -(CH2)qX- wherein the -(CH2)q- group is attached to Ar2, or -X(CH2)q- wherein X is attached to Ar2, and wherein any of the -CH2- groups may be optionally substituted by one or more C1-6alkyl groups; X represents oxygen, -CH(OR5)-, -NR5- or -CH2- wherein the -CH2- group may be optionally substituted by one or more C1-6alkyl groups; R3 and R4 each independently represent hydrogen, C1-6alkyl or, together with the nitrogen or other atoms to which they are attached, form an azacycloalkyl ring or an oxo-substituted azacycloalkyl ring; R5 represents hydrogen or C1-6alkyl; m and n independently represent an integer selected from 1 and 2; p independently represents an integer selected from 0, 1, 2 and 3; q independently represents an integer selected from 0, 1, 2 and 3; or a pharmaceutically acceptable salt or solvate thereof, with the proviso that when Ar1 is a pyridyl group, and Z is -CH2X- where X is attached to the Ar1 group, X is selected from -CH(OR5)-, -NR5- and -CH2- wherein the -CH2- group may be optionally substituted by one or more C1-6alkyl groups. The compounds of formula (I) are useful in therapy, in particular as antipsychotic agents.

  该发明提供了以下式（I）的化合物：其中A和B分别代表基团-(CH2)m-和-(CH2)n-；R1代表氢或C1-6烷基；R2代表氢、卤素、羟基、氰基、硝基、羟基C1-6烷基、三氟甲基、三氟甲氧基、C1-6烷基、C1-6烷氧基、C1-6氟烷氧基、-(CH2)pC3-6环烷基、-(CH2)pOC3-6环烷基、-COC1-6烷基、-SO2 C1-6烷基、-SOC1-6烷基、-S-C1-6烷基、-CO2C1-6烷基、-CO2NR3R4、-SO2NR3R4、-(CH2)pNR3R4、-(CH2)pNR3COR4、可选择地取代的芳基环、可选择地取代的杂芳基环、融合的双环杂芳基环系统或可选择地取代的杂环烷基环；Ar1代表可选择地取代的杂芳基环；Ar2代表可选择地取代的芳基环或可选择地取代的杂芳基环；Z代表-(CH2)qX-其中-(CH2)q-基团连接到Ar2，或-X(CH2)q-其中X连接到Ar2，并且任何一个-CH2-基团可以可选择地由一个或多个C1-6烷基基团取代；X代表氧、-CH(OR5)-、-NR5-或-CH2-其中-CH2-基团可以可选择地由一个或多个C1-6烷基基团取代；R3和R4各自独立地代表氢、C1-6烷基或者与它们连接的氮或其他原子形成氮杂环烷基环或氧代取代的氮杂环烷基环；R5代表氢或C1-6烷基；m和n独立地代表选自1和2的整数；p独立地代表选自0、1、2和3的整数；q独立地代表选自0、1、2和3的整数；或其药学上可接受的盐或溶剂，但当Ar1是吡啶基团，且Z为-CH2X-其中X连接到Ar1基团时，X选自-CH(OR5)-、-NR5-和-CH2-其中-CH2-基团可以可选择地由一个或多个C1-6烷基基团取代。该式（I）的化合物在治疗中特别作为抗精神病药物具有用途。
• 7-Heteroarylsulfonyl-tetrahydro-3-benzazepine derivatives as antipsychotic agents
  申请人：Cooper Gwyn David

  公开号：US20070093473A1

  公开（公告）日：2007-04-26

  The invention provides compounds of formula (I): wherein A and B represent the groups —(CH 2 ) m — and —(CH 2 ) n — respectively; R 1 represents hydrogen or C 1-6 alkyl; R 2 represents hydrogen, halogen, hydroxy, cyano, nitro, hydroxyC 1-6 alkyl, trifluoromethyl, trifluoromethoxy, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 fluoroalkoxy, —(CH 2 ) p C 3-6 cycloalkyl, —(CH 2 ) p OC 3-6 cycloalkyl, —COC 1-6 alkyl, —SO 2 C 1-6 alkyl, —SOC 1-6 alkyl, —S—C 1-6 alkyl, —CO 2 C 1-6 alkyl, —CO 2 NR 3 R 4 , —SO 2 NR 3 R 4 , —(CH 2 ) p NR 3 R 4 , —(CH 2 ) p NR 3 COR 4 , optionally substituted aryl ring, optionally substituted heteroaryl ring, a fused bicyclic heteroaromatic ring system or optionally substituted heterocyclyl ring; Ar 1 represents optionally substituted heteroaryl ring; Ar 2 represents optionally substituted aryl ring or optionally substituted heteroaryl ring; Z represents —(CH 2 ) q X— wherein the —(CH 2 ) q — group is attached to Ar 2 , or —X(CH 2 ) q — wherein X is attached to Ar 2 , and wherein any of the —CH 2 — groups may be optionally substituted by one or more C 1-6 alkyl groups; X represents oxygen, —CH(OR 5 )—, —NR 5 — or —CH 2 — wherein the —CH 2 — group may be optionally substituted by one or more C 1-6 alkyl groups; R 3 and R 4 each independently represent hydrogen, C 1-6 alkyl or, together with the nitrogen or other atoms to which they are attached, form an azacycloalkyl ring or an oxo-substituted azacycloalkyl ring; R 5 represents hydrogen or C 1-6 alkyl; m and n independently represent an integer selected from 1 and 2; p independently represents an integer selected from 0, 1, 2 and 3; q independently represents an integer selected from 0, 1, 2 and 3; or a pharmaceutically acceptable salt or solvate thereof, with the proviso that when Ar 1 is a pyridyl group, and Z is —CH 2 X— where X is attached to the Ar 1 group, X is selected from —CH(OR 5 )—, —NR 5 — and —CH 2 — wherein the —CH 2 — group may be optionally substituted by one or more C 1-6 alkyl groups. The compounds of formula (I) are useful in therapy, in particular as antipsychotic agents.

  本发明提供式（I）的化合物： 其中A和B分别代表基团—（CH2）m—和—（CH2）n—； R1代表氢或C1-6烷基； R2代表氢、卤素、羟基、氰基、硝基、羟基C1-6烷基、三氟甲基、三氟甲氧基、C1-6烷基、C1-6烷氧基、C1-6氟烷氧基、—（CH2）pC3-6环烷基、—（CH2）pOC3-6环烷基、—COC1-6烷基、—SO2C1-6烷基、—SOC1-6烷基、—S—C1-6烷基、—CO2C1-6烷基、—CO2NR3R4、—SO2NR3R4、—（CH2）pNR3R4、—（CH2）pNR3COR4、可选地取代的芳环、可选地取代的杂环、融合的双环杂芳基环系统或可选地取代的杂环基； Ar1代表可选地取代的杂环基； Ar2代表可选地取代的芳环或可选地取代的杂环基； Z代表—（CH2）qX—，其中—（CH2）q—基团连接到Ar2，或—X（CH2）q—，其中X连接到Ar2，其中任何一个—CH2—基团可选择地被一个或多个C1-6烷基基团取代； X代表氧、—CH（OR5）—、—NR5—或—CH2—，其中—CH2—基团可以选择地被一个或多个C1-6烷基基团取代； R3和R4各自独立地代表氢、C1-6烷基或与它们连接的氮或其他原子形成一个氮杂环烷基环或一个氧代取代的氮杂环烷基环； R5代表氢或C1-6烷基； m和n独立地代表选自1和2的整数； p独立地代表选自0、1、2和3的整数； q独立地代表选自0、1、2和3的整数； 或其药学上可接受的盐或溶剂，但当Ar1是吡啶基团，且Z为—CH2X—，其中X连接到Ar1基团时，X选自—CH（OR5）—、—NR5—和—CH2—，其中—CH2—基团可以选择地被一个或多个C1-6烷基基团取代。 式（I）的化合物在治疗中有用，特别是作为抗精神病药物。