4-[4-(trifluoromethyl)phenyl]-1H-pyridazin-6-one | 697739-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-[4-(trifluoromethyl)phenyl]-1H-pyridazin-6-one
• 英文别名: 5-[4-trifluorophenyl]pyridazin-3(2H)-one；5-(4-(trifluoromethyl)phenyl)pyridazin-3(2H)-one
• CAS: 697739-27-8
• 化学式: C₁₁H₇F₃N₂O
• mdl: MFCD27927542
• 分子量: 240.185
• InChiKey: XKTPUDPIKVKANM-UHFFFAOYSA-N

物化性质

• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[4-(trifluoromethyl)phenyl]-1H-pyridazin-6-one 在 三氯氧磷 作用下， 反应 5.0h， 生成 3-chloro-5-[4-(trifluoromethyl)phenyl]pyridazine
  参考文献：
  名称：

  [EN] AMINO-HETEROCYCLES AS VR-1 ANTAGONISTS FOR TREATING PAIN
  [FR] HETEROCYCLES AMINES EN TANT QU'ANTAGONISTES DU RECEPTEUR VANILLOIDE (VR-1) POUR LE TRAITEMENT DE LA DOULEUR

  摘要：

  本发明提供了一种具有以下结构的化合物（I）：其中V代表NR5、O、S、SO或S(O)2；W和X分别独立地代表CH或N；Y代表N、CH或C-Ar2，但至少有一个但不超过两个W、X和Y为N；Z代表CH或C-Ar2，但当Y为N或CH时，则Z为C-Ar2，并进一步规定当Y为C-Ar2时，Z为CH；Ar1代表包含一个、两个、三个或四个从氮、氧和硫中选择的杂原子的融合的9或10成员杂双环系统，其中所述环系中的至少一个环是芳香的；Ar2代表选择自苯基、吡啶基、嘧啶基和吡啶嗪基的芳香环，可以是可选地融合和取代的；R1代表卤素、羟基、氧、C1-6烷基、C2-6烯基、C2-6炔基、卤代C1-6烷基、羟基C1-6烷基、C1-6烷氧基、卤代C1-6烷氧基、羟基C1-6烷氧基、C3-7环烷基、C3-7环烷氧基、C3-5环烷基C1-4烷基、氰基、硝基、SR6、SOR6、SO2R6、COR6、NR3COR6、CONR3R4、NR3SO2R6、SO2NR3R4、-(CH2)m羧基、酯化的-(CH2)m羧基或-(CH2)mNR3R4；R2代表氢、卤素、羟基、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、卤代C1-6烷氧基、未取代的苯基或苯基，其上取代有一个或两个从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择的基团；R3和R4各自独立地代表氢、C1-6烷基、C2-6烯基、C2-6炔基、C3-7环烷基或氟代C1-6烷基；或R3和R4和它们连接的氮原子共同形成一个由4到7个环原子组成的杂原烷环，可选地取代为一个或两个从羟基或C1-4烷氧基中选择的基团，该环可能可选地包含作为所述环原子之一的氧或硫原子、S(O)、S(O)2或NR5；R5代表氢、C1-4烷基、羟基C1-4烷基或C1-4烷氧基C1-4烷基；R6代表氢、C1-6烷基、氟代C1-6烷基、C3-7环烷基、未取代的苯基或苯基，其上取代有一个或两个从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择的基团；m为零或从1到4的整数；n为零或从1到3的整数；或其药学上可接受的盐、N-氧化物或前药；包含它的药物组合物；其在治疗方法中的用途；用于制造用于治疗VR-1相关病症的药物，例如疼痛和/或炎症占优势的病症的用途；以及使用它的治疗方法。

  公开号：

  WO2004046133A1
• 作为产物：
  描述：

  3-Phenylmethoxy-5-[4-(trifluoromethyl)phenyl]pyridazine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以37 mg的产率得到4-[4-(trifluoromethyl)phenyl]-1H-pyridazin-6-one
  参考文献：
  名称：

  NOVEL NITROGEN-CONTAINING AROMATIC HETEROCYCLIC COMPOUND

  摘要：

  公开号：

  EP3381904B1
• 作为试剂：
  描述：

  三环己基膦 、 5-碘哒嗪-3(2H)-酮 、 4-三氟甲基苯硼酸 、 Tripotassium;phosphate 在 醋酸钯 4-[4-(trifluoromethyl)phenyl]-1H-pyridazin-6-one 作用下， 以 甲苯 、 水 、 二氯甲烷 为溶剂， 反应 22.0h， 以to afford the desired product 5-(4-(trifluoromethyl)phenyl)pyridazin-3(2H)-one 18A (14.8 mg, 0.06 mmol, 39.1% yield) as a white solid的产率得到4-[4-(trifluoromethyl)phenyl]-1H-pyridazin-6-one
  参考文献：
  名称：

  Aza pyridone analogs useful as melanin concentrating hormone receptor-1 antagonists

  摘要：

  提供具有以下公式I的MCHR1拮抗剂：其中所有变量均在此定义。这些化合物对于治疗MCHR1介导的疾病，如肥胖症、糖尿病、炎症性肠病、抑郁症和焦虑症非常有用。

  公开号：

  US08278316B2

文献信息

• [EN] AZA PYRIDONE ANALOGS USEFUL AS MELANIN CONCENTRATING HORMONE RECEPTOR-1 ANTAGONISTS<br/>[FR] ANALOGUES D'AZAPYRIDONE UTILES COMME ANTAGONISTES DU RÉCEPTEUR 1 DE L'HORMONE CONCENTRANT LA MÉLANINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2010104818A1

  公开（公告）日：2010-09-16

  MCHR1 antagonists are provided having the following Formula (I): A1 and A2 are independently C or N; E is C or N; Q1, Q2, and Q3 are independently C or N provided that at least one of Q1, Q2, and Q3 is N but not more than one of Q1, Q2, and Q3 is N; D1 is a bond, -CR8R9 X-, -XCR8R9-, -CHR8CHR9-, -CR10=CR10'-, -C≡C-, or 1,2-cyclopropyl; X is O, S or NR11; R1, R2, and R3 are independently selected from the group consisting of hydrogen, halogen, lower alkyl, lower cycloalkyl, -CF3, -OCF3, -OR12 and -SR12; G is O, S or -NR15; D2 is lower alkyl, lower cycloalkyl, lower alkylcycloalkyl, lower cycloalkylalkyl, lower cycloalkoxyalkyl or lower alkylcycloalkoxy or when G is NR15, G and D2 together may optionally form an azetidine, pyrrolidine or piperidine ring; Z1 and Z2 are independently hydrogen, lower alkyl, lower cycloalkyl, lower alkoxy, lower cycloalkoxy, halo, -CF3, -OCONR14R14', -CN, -CONR14R14', -SOR12, -SO2R12, -NR14COR14', -NR14CO2R14', -CO2R12, NR14SO2R12 or COR12; R5, R6, and R7 are independently selected from the group consisting of hydrogen lower alkyl, lower cycloalkyl, -CF3, -SR12, lower alkoxy, lower cycloalkoxy, -CN, -CONR14R14', SOR12, SO2R12, NR14COR14', NR14CO2R12, CO2R12, NR14SO2R12 and -COR12; R8, R9, R10, R10', R11 are independently hydrogen or lower alkyl; R12 is lower alkyl or lower cycloalkyl; R14 and R14' are independently H, lower alkyl, lower cycloalkyl or R14 and R14' together with the N to which they are attached form a ring having 4 to 7 atoms; and R15 is independently selected from the group consisting of hydrogen and lower alkyl. Such compounds are useful for the treatment of MCHR1 mediated diseases, such as obesity, diabetes, IBD, depression, and anxiety.

  MCHR1拮抗剂具有以下化学式（I）：A1和A2独立地为C或N；E为C或N；Q1、Q2和Q3独立地为C或N，但至少其中一个为N，但不超过一个为N；D1为键，-CR8R9 X-，-XCR8R9-，-CHR8CHR9-，-CR10=CR10'-，-C≡C-，或1,2-环丙基；X为O、S或NR11；R1、R2和R3独立地从氢、卤素、低烷基、低环烷基、-CF3、-O 、-OR12和-SR12组成的群体中选择；G为O、S或-NR15；D2为低烷基、低环烷基、低烷基环烷基、低环烷基烷基、低环烷氧基烷基或低烷基环烷氧基，或当G为NR15时，G和D2一起可以选择形成氮杂环丙烷、吡咯烷或哌啶环；Z1和Z2独立地为氢、低烷基、低环烷基、低烷氧基、低环烷氧基、卤素、- 、-OCONR14R14'、-CN、-CONR14R14'、-SOR12、-SO2R12、-NR14COR14'、-NR14CO2R14'、-CO2R12、NR14SO2R12或COR12；R5、R6和R7独立地从氢、低烷基、低环烷基、- 、-SR12、低烷氧基、低环烷氧基、-CN、-CONR14R14'、SOR12、SO2R12、NR14COR14'、NR14CO2R12、CO2R12、NR14SO2R12和-COR12组成的群体中选择；R8、R9、R10、R10'、R11独立地为氢或低烷基；R12为低烷基或低环烷基；R14和R14'独立地为H、低烷基、低环烷基或R14和R14'与其连接的N一起形成具有4至7个原子的环；R15独立地从氢和低烷基组成的群体中选择。这些化合物对于治疗MCHR1介导的疾病，如肥胖症、糖尿病、炎症性肠病、抑郁症和焦虑症非常有用。
• HETEROCYCLIC SULFONAMIDE DERIVATIVE AND MEDICINE COMPRISING SAME
  申请人：EA PHARMA CO., LTD.

  公开号：US20160332999A1

  公开（公告）日：2016-11-17

  The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the DESCRIPTION, or a pharmaceutically acceptable salt thereof. The compound has a superior TRPA1 antagonist activity, and can provide a medicament useful for the prophylaxis or treatment of diseases involving TRPA1 antagonist and TRPA1.

  本发明提供了一种由公式(I)表示的化合物： 其中，每个符号如说明书中所定义，或者其药用可接受的盐。该化合物具有优越的TRPA1拮抗剂活性，并且可以提供一种用于预防或治疗涉及TRPA1拮抗剂和TRPA1的疾病的药物。
• [EN] (1-AZINONE) -SUBSTITUTED PYRIDOINDOLES AS MCH ANTAGONISTS<br/>[FR] PYRIDOINDOLES (1-AZINONE)-SUBSTITUÉS EN TANT QU'ANTAGONISTES MCH
  申请人：ALBANY MOLECULAR RES INC

  公开号：WO2009089482A1

  公开（公告）日：2009-07-16

  Substituted pyridoindoles for incorporation in pharmaceutical compositions employed in the treatment of various diseases correspond to formula (I) wherein R1 is H or optionally substituted alkyl; R2, R3, R4 are each independently selected from H, -O-alkyl, -S-alkyl, alkyl, halo, -CF3, and -CN; G is -CR12R13-NR5- or -NR5-CR12R13; R5 is H, optionally substituted alkyl, optionally substituted heterocycle, -C(=O)-R6, -C(=O)-O-R7, or -C(=O)-NR19R20; R6 and R7 are each optionally substituted alkyl or optionally substituted heterocycle; R8, R9, R10, R11, R12, R13, R19 and R20 are each independently selected from H or optionally substituted alkyl; R14 and R15 are each independently H or halogen; L is -CH2-O-, -CH2CH2-, -CH=CH- or a bond; and B is aryl or heteroaryl or cycloalkyl; with the proviso that, when L is a direct bond, B cannot be unsubstituted heteroaryl or heteroaryl monosubstituted with fluorine.

  将吡啶吲哚替代物用于制药组合物中，用于治疗各种疾病，对应于式（I），其中R1为H或可选择的取代烷基；R2、R3、R4分别独立选择自H、-O-烷基、-S-烷基、烷基、卤素、-CF3和-CN；G为-CR12R13-NR5-或-NR5-CR12R13；R5为H、可选择的取代烷基、可选择的取代杂环、-C(=O)-R6、-C(=O)-O-R7或-C(=O)-NR19R20；R6和R7分别为可选择的取代烷基或可选择的取代杂环；R8、R9、R10、R11、R12、R13、R19和R20分别独立选择自H或可选择的取代烷基；R14和R15分别独立为H或卤素；L为-CH2-O-、- -、-CH=CH-或一个键；B为芳基或杂芳基或环烷基；但条件是，当L为直接键时，B不能是未取代的杂芳基或单取代氟的杂芳基。
• Amino-heterocycles as vr-1 antagonists for treating pain
  申请人：Blurton Peter

  公开号：US20060040947A1

  公开（公告）日：2006-02-23

  the present invention provides a compound of formula (I): wherein V represents NR 5 , O, S, SO or S(O) 2 ; W and X each independently represent CH or N; Y represents N, CH or C—Ar 2 , with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C—Ar 2 , with the proviso that when Y is N or CH then Z is C—Ar 2 , and with the further proviso that when Y is C—Ar 2 then Z is CH; Ar 1 represents a fused 9 or 10 membered heterobicyclic ring system containing one, two, three or four heteroatoms selected from nitrogen, oxygen and sulfur, wherein at least one of the rings in said ring system is aromatic; Ar 2 represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R 1 represents halogen, hydroxy, oxo, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, haloC 1-6 alkyl, hydroxyC 1-6 alkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, hydroxyC 1-6 alkoxy, C 3-7 cycloalkyl, C 3-7 cycloalkoxy, C 3-5 cycloalkylC 1-4 alkyl, cyano, nitro, SR 6 , SOR 6 , SO 2 R 6 , COR 6 , NR 3 COR 6 , CONR 3 R 4 , NR 3 SO 2 R 6 , SO 2 NR 3 R 4 , —(CH 2 ) m carboxy, esterified —(CH 2 ) m carboxy or —(CH 2 ) m NR 3 R 4 ; R 2 represents hydrogen, halogen, hydroxy, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy, haloC 1-6 alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy or haloC 1-6 alkoxy; R 3 and R 4 are each independently hydrogen, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-7 cycloalkyl or fluoroC 1-6 alkyl; or R 3 and R 4 and the nitrogen atom to which they are attached together form a heteroaliphatic ring of 4 to 7 ring atoms, optionally substituted by one or two groups selected from hydroxy or C 1-4 alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O) 2 , or NR 5 ; R 5 represents hydrogen, C 1-4 alkyl, hydroxyC 1-4 alkyl or C 1-4 alkoxyC 1-4 alkyl; R 6 represents hydrogen, C 1-6 alkyl, fluoroC 1-6 alkyl, C 3-7 cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C 1-6 alkyl, haloC 1-6 alkyl, C 3-7 cycloalkyl, C 1-6 alkoxy or haloC 1-6 alkoxy; m is either zero or an integer from 1 to 4; n is either zero or an integer from 1 to 3; or a pharmaceutically acceptable salt, N-oxide or a prodrug thereof; a pharmaceutical composition comprising it; its use in methods of treatment; use of it for the manufacture of a medicament for treating VR-1 related conditions such as those in which pain and/or inflammation predominate; and methods of treatment using it.

  本发明提供了一种化合物，其化学式为（I）：其中V代表NR5、O、S、SO或S（O）2；W和X各自独立地代表CH或N；Y代表N、CH或C-Ar2，但至少有一个，但不超过两个，W、X和Y是N；Z代表CH或C-Ar2，但当Y为N或CH时，Z为C-Ar2，且进一步规定当Y为C-Ar2时，Z为CH；Ar1代表一个融合的9或10个成员的杂双环环系统，其中包含从氮、氧和硫中选择的一个、两个、三个或四个杂原子，其中至少一个环为芳香环；Ar2代表一种芳香环，选择自苯基、吡啶基、嘧啶基和吡啶嗪基，可选地融合和取代；R1代表卤素、羟基、氧代、C1-6烷基、C2-6烯基、C2-6炔基、卤代C1-6烷基、羟基C1-6烷基、C1-6烷氧基、卤代C1-6烷氧基、羟基C1-6烷氧基、C3-7环烷基、C3-7环烷氧基、C3-5环烷基C1-4烷基、氰基、硝基、SR6、SOR6、SO2R6、COR6、NR3COR6、CONR3R4、NR3SO2R6、SO2NR3R4、-(CH2)m羧基、酯化的-( )m羧基或-( )mNR3R4；R2代表氢、卤素、羟基、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基、卤代C1-6烷氧基、未取代苯基或取代一个或两个群的苯基，所述群从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择；R3和R4各自独立地代表氢、C1-6烷基、C2-6烯基、C2-6炔基、C3-7环烷基或氟代C1-6烷基；或R3和R4及它们所连接的氮原子一起形成4至7个环原子的杂脂环，可选地取代一个或两个群，所述群从羟基或C1-4烷氧基中选择，该环可以选择地包含一个氧原子或硫原子、S（O）、S（O）2或NR5作为其中一个所述环原子；R5代表氢、C1-4烷基、羟基C1-4烷基或C1-4烷氧基C1-4烷基；R6代表氢、C1-6烷基、氟代C1-6烷基、C3-7环烷基、未取代苯基或取代一个或两个群的苯基，所述群从卤素、C1-6烷基、卤代C1-6烷基、C3-7环烷基、C1-6烷氧基或卤代C1-6烷氧基中选择；m为零或1至4的整数；n为零或1至3的整数；或其药学上可接受的盐、N-氧化物或前药；包含它的制药组合物；它在治疗方法中的用途；用于制造治疗VR-1相关疾病的药物，例如疼痛和/或炎症占主导地位的疾病；以及使用它的治疗方法。
• (1-AZINONE)-SUBSTITUTED PYRIDOINDOLES
  申请人：GUZZO Peter Robert

  公开号：US20090275590A1

  公开（公告）日：2009-11-05

  Substituted pyridoindoles for incorporation in pharmaceutical compositions employed in the treatment of various diseases correspond to formula (I) wherein R 1 is H or optionally substituted alkyl; R 2 , R 3 , R 4 are each independently selected from H, —O-alkyl, —S-alkyl, alkyl, halo, —CF 3 , and —CN; G is —CR 12 R 13 —NR 5 — or —NR 5 —CR 12 R 13 ; R 5 ; is H, optionally substituted alkyl, optionally substituted heterocycle, —C(═O)—R 6 , —C(═O)—O—R 7 , or —C(═O)—NR 19 R 20 ; R 6 and R 7 are each optionally substituted alkyl or optionally substituted heterocycle; R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 19 and R 20 are each independently selected from H or optionally substituted alkyl; R 14 and R 15 are each independently H or halogen; L is —CH 2 —O—, —CH 2 CH 2 —, —CH═CH— or a bond; and B is aryl or heteroaryl or cycloalkyl; with the proviso that, when L is a direct bond, B cannot be unsubstituted heteroaryl or heteroaryl monosubstituted with fluorine.

  替代吡啶并吡唑类化合物可用于制备用于治疗各种疾病的药物组合物，其对应于式（I），其中R1是H或可选择的取代烷基; R2，R3，R4分别选自H，—O-烷基，—S-烷基，烷基，卤素，—CF3和—CN; G是—CR12R13—NR5—或—NR5—CR12R13; R5;是H，可选择的取代烷基，可选择的取代杂环，—C（═O）—R6，—C（═O）—O—R7或—C（═O）—NR19R20; R6和R7分别是可选择的取代烷基或可选择的取代杂环; R8，R9，R10，R11，R12，R13，R19和R20分别选自H或可选择的取代烷基; R14和R15分别是H或卤素; L是—CH2—O—，— —，—CH═CH—或键; B是芳基或杂芳基或环烷基; 前提是，当L是直接键时，B不能是未取代的杂芳基或单取代氟的杂芳基。