3-(4-trifluoromethylphenyl)maleic anhydride | 659729-88-1

• 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: 3-(4-trifluoromethylphenyl)maleic anhydride
• 英文别名: 2,5-Furandione, 3-[4-(trifluoromethyl)phenyl]-；3-[4-(trifluoromethyl)phenyl]furan-2,5-dione
• CAS: 659729-88-1
• 化学式: C₁₁H₅F₃O₃
• 分子量: 242.154
• InChiKey: IWSYDYHOZQOQEU-UHFFFAOYSA-N

物化性质

• 沸点：
  331.5±42.0 °C(Predicted)
• 密度：
  1.497±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 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：
  43.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(4-trifluoromethylphenyl)maleic anhydride 在 溶剂黄146 、 肼 作用下， 以 水 为溶剂， 反应 3.0h， 生成 4-[4-(Trifluoromethyl)phenyl]-1,2-dihydropyridazine-3,6-dione
  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：

  对三氟甲基苯乙腈 在 甲酸 、 硫酸 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 19.0h， 生成 3-(4-trifluoromethylphenyl)maleic anhydride
  参考文献：
  名称：

  通过光氧化还原催化 α-含氧酸和马来酸酐的双重脱羧偶联一步合成 γ-酮酸

  摘要：

  开发了一种从 α-酮酸一步合成 γ-酮酸的光催化方法。该方法采用马来酸酐作为丙烯酸的无痕合成等价物，通过双重脱羧策略实现选择性交叉偶联，其中分子CO 2作为唯一的废物副产物被释放。该方法还得到了扩展，可将高度区域选择性的三组分与各种醇偶联，以获得功能化的 γ-酮酯。

  DOI：

  10.1021/acs.orglett.3c03258

文献信息

• [EN] SUBSTITUTED AMINO HETEROCYCLES AS VR-1 ANTAGONISTS FOR TREATING PAIN<br/>[FR] AMINO-HETEROCYCLES SUBSTITUES EN TANT QU'ANTAGONISTES DU VR-1 POUR TRAITER LA DOULEUR
  申请人：MERCK SHARP & DOHME

  公开号：WO2004074290A1

  公开（公告）日：2004-09-02

  The present invention provides compounds of formula I: in which: one of T1 and T4 is N and the other is C; T2 and T3 are independently N or C(CH2)nR2; X, Y and Z are independently N or C(CH2)nR3; R1 is Ar1 or R1 is C1-6alkyl optionally substituted with one or two groups Ar1; Ar1 is an optionally substituted cyclohexyl, piperidinyl, piperazinyl, morpholinyl, adamantyl, phenyl, naphthyl, a six-membered heteroaromatic ring containing one, two or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one O or S atom being present, or a nine- or ten-membered bicyclic heteroaromatic ring in which phenyl or a six-membered heteroaromatic ring as defined above is fused to a six-or five-membered heteroaromatic ring as defined above; Ar is an optionally substituted phenyl, a six-membered heteroaromatic ring containing one, two or three nitrogen atoms or a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one heteroatom being O or S, Ar being optionally substituted by one, two or three groups chosen from halogen, CF3, OCF3, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, nitro, cyano, isonitrile, hydroxy, C1-6alkoxy, C1-6alkylthio, -NR6R7, -CONR6R7, -COH, CO2H, C1-6alkoxycarbonyl, haloC1-6alkyl, hydroxyC1-6alkyl, aminoC1-6alkyl, C1-6alkylcarbonyl and a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one heteroatom being O or S, optionally substituted by C1-6alkyl, halogen, amino, hydroxy or cyano; or a pharmaceutically acceptable salt thereof as a VR-1 ligand; pharmaceutical compositions comprising it; its use in therapy; use of it in the manufacture of a medicament to treat pain; and methods of treating subjects suffering from pain.

  本发明提供了式I的化合物：其中：T1和T4中的一个是N，另一个是C; T2和T3独立地是N或C（CH2）nR2; X，Y和Z独立地是N或C（CH2）nR3; R1是Ar1或R1是C1-6烷基，可选地取代一个或两个Ar1基团; Ar1是可选取代的环己基，哌啶基，哌嗪基，吗啉基，金刚烷基，苯基，萘基，一个六元杂环芳香环，其中含有一个，两个或三个氮原子，一个五元杂环芳香环，其中选择了一个，两个，三个或四个杂原子从O，N和S中选择，最多只有一个O或S原子存在，或一个九元或十元的双环杂芳香环，其中苯基或上述定义的六元杂环芳香环与上述定义的六元或五元杂环芳香环融合; Ar是可选取代的苯基，一个含有一个，两个或三个氮原子的六元杂环芳香环或一个含有一个，两个，三个或四个从O，N和S中选择的杂原子的五元杂环芳香环，最多只有一个杂原子是O或S，Ar可选地取代由卤素，CF3，OCF3，C1-6烷基，C2-6烯基，C2-6炔基，硝基，氰基，异腈基，羟基，C1-6烷氧基，C1-6烷基硫基，-NR6R7，-CONR6R7，-COH，CO2H，C1-6烷氧羰基，卤代C1-6烷基，羟基C1-6烷基，氨基C1-6烷基，C1-6烷基羰基和一个含有一个，两个，三个或四个从O，N和S中选择的杂原子的五元杂环芳香环，最多只有一个杂原子是O或S，可选地被C1-6烷基，卤素，氨基，羟基或氰基取代;或其药学上可接受的盐作为VR-1配体;包含它的制药组合物;其在治疗中的用途;将其用于制造治疗疼痛的药物;以及治疗患有疼痛的受试者的方法。
• [EN] VANILLOID RECEPTOR LIGANDS AND THEIR USE IN TREATMENTS<br/>[FR] LIGANDS DE RECEPTEUR VANILLOIDE ET LEUR UTILISATION DANS DES TRAITEMENTS
  申请人：AMGEN INC

  公开号：WO2004014871A1

  公开（公告）日：2004-02-19

  Compounds having the general structure and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  含有通用结构和组成的化合物及其组合物，用于治疗急性、炎症性和神经痛、牙痛、普通头痛、偏头痛、集群性头痛、混合性血管和非血管综合症、紧张性头痛、普通炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠病、炎症性眼病、炎症性或不稳定的膀胱疾病、牛皮癣、带有炎症成分的皮肤病、慢性炎症状况、炎症性疼痛及相关的高敏性和触痛，神经痛及相关的高敏性和触痛、糖尿病神经病疼痛、烧伤后神经痛、交感神经维持的疼痛、去神经症候群、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸道、泌尿生殖系统、胃肠道或血管区域的内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、普通胃肠疾病、胃溃疡、十二指肠溃疡、腹泻、坏死性剂引起的胃病变、毛发生长、血管运动或过敏性鼻炎、支气管疾病或膀胱疾病。
• Vanilloid receptor ligands and their use in treatments
  申请人：——

  公开号：US20040082780A1

  公开（公告）日：2004-04-29

  Compounds having the general structure 1 and compositions containing them, for the treatment of acute, inflammatory and neuropathic pain, dental pain, general headache, migraine, cluster headache, mixed-vascular and non-vascular syndromes, tension headache, general inflammation, arthritis, rheumatic diseases, osteoarthritis, inflammatory bowel disorders, inflammatory eye disorders, inflammatory or unstable bladder disorders, psoriasis, skin complaints with inflammatory components, chronic inflammatory conditions, inflammatory pain and associated hyperalgesia and allodynia, neuropathic pain and associated hyperalgesia and allodynia, diabetic neuropathy pain, causalgia, sympathetically maintained pain, deafferentation syndromes, asthma, epithelial tissue damage or dysfunction, herpes simplex, disturbances of visceral motility at respiratory, genitourinary, gastrointestinal or vascular regions, wounds, burns, allergic skin reactions, pruritus, vitiligo, general gastrointestinal disorders, gastric ulceration, duodenal ulcers, diarrhea, gastric lesions induced by necrotising agents, hair growth, vasomotor or allergic rhinitis, bronchial disorders or bladder disorders.

  具有一般结构1的化合物及其组成物，用于治疗急性、炎症和神经痛、牙痛、普通头痛、偏头痛、集群头痛、混合血管和非血管综合症、紧张性头痛、普通炎症、关节炎、风湿性疾病、骨关节炎、炎症性肠病、炎症性眼疾、炎症性或不稳定的膀胱疾病、牛皮癣、具有炎症成分的皮肤病、慢性炎症状况、炎症性疼痛及相关的高敏感性和触痛、神经痛及相关的高敏感性和触痛、糖尿病神经病痛、烧灼性疼痛、交感神经维持性疼痛、去神经症候群、哮喘、上皮组织损伤或功能障碍、单纯疱疹、呼吸、泌尿、胃肠或血管区域的内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒、白癜风、普通胃肠障碍、胃溃疡、十二指肠溃疡、腹泻、坏死剂诱导的胃病变、毛发生长、血管运动或过敏性鼻炎、支气管疾病或膀胱疾病。
• Substituted amino heterocycles as vr-1 antagonists for treating pain
  申请人：Brown Elizabeth Rebecca

  公开号：US20060154930A1

  公开（公告）日：2006-07-13

  The present invention provides compounds of formula I: in which: one of T 1 and T 4 is N and the other is C; T 2 and T 3 are independently N or C(CH 2 ) n R 2 ; X, Y and Z are independently N or C(CH 2 ) n R 3 ; R 1 is Ar 1 or R 1 is C 1-6 alkyl optionally substituted with one or two groups Ar1; Ar1 is an optionally substituted cyclohexyl, piperidinyl, piperazinyl, morpholinyl, adamantyl, phenyl, naphthyl, a six membered heteroaromatic ring containing one, two or three nitrogen atoms, a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one O or S atom being present, or a nine- or ten-membered bicyclic heteroaromatic ring in which phenyl or a six-membered heteroaromatic ring as defined above is fused to a six- or five-membered heteroaromatic ring as defined above; Ar is an optionally substituted phenyl, a six-membered heteroaromatic ring containing one, two or three nitrogen atoms or a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one heteroatom being O or S, Ar being optionally substituted by one, two or three groups chosen from halogen, CF 3 , OCF 3 , C 1-6 -alkyl, C 2-6 alkenyl, C 2-6 alkynyl, nitro, cyano, isonitrile, hydroxy, C 1-6 alkoxy, C 1-6 alkylthio, —NR 6 R 7 , —CONR 6 R 7 , —COH, CO 2 H, C 1-6 alkoxycarbonyl, haloC 1-4 alkyl, hydroxyC 1-6 alkyl, aminoC 1-6 alkyl, C 1-4 alkylcarbonyl and a five-membered heteroaromatic ring containing one, two, three or four heteroatoms chosen from O, N and S, at most one heteroatom being O or S, optionally substituted by C 1-6 alkyl, halogen, amino, hydroxy or cyano; or a pharmaceutically acceptable salt thereof as a VR-1 ligand; pharmaceutical compositions comprising it; its use in therapy; use of it in the manufacture of a medicament to treat pain; and methods of treating subjects suffering from pain.

  本发明提供了公式I的化合物：其中：T1和T4中的一个是N，另一个是C; T2和T3分别是N或C（CH2）nR2; X，Y和Z分别是N或C（CH2）nR3; R1是Ar1或R1是C1-6烷基，可选地取代一个或两个Ar1基团; Ar1是可选地取代的环己基，哌啶基，哌嗪基，吗啉基，金刚烷基，苯基，萘基，含有一个，两个或三个氮原子的六元杂环芳烃环，含有一，两，三或四个O，N和S杂原子的五元杂环芳烃环，最多只有一个O或S原子存在，或者是将苯基或上述定义的六元杂环芳烃环与上述定义的六元或五元杂环芳烃环融合而成的九元或十元双环杂环芳烃环; Ar是可选地取代的苯基，含有一个，两个或三个氮原子的六元杂环芳烃环或含有一，两个，三个或四个O，N和S杂原子的五元杂环芳烃环，最多只有一个杂原子为O或S，Ar可被一，两或三个由卤素，CF3，OCF3，C1-6烷基，C2-6烯基，C2-6炔基，硝基，氰基，异腈基，羟基，C1-6烷氧基，C1-6烷基硫基，-NR6R7，-CONR6R7，-COH，CO2H，C1-6烷氧基羰基，卤代C1-4烷基，羟基C1-6烷基，氨基C1-6烷基，C1-4烷基羰基和含有一，两个，三个或四个O，N和S杂原子的五元杂环芳烃环取代的基团取代;或其药学上可接受的盐作为VR-1配体;包含它的制药组合物;其在治疗中的应用;将其用于制造治疗疼痛的药物;以及治疗疼痛患者的方法。
• 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-(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。