4-氯-6-(4-(三氟甲基)苯基)嘧啶 | 659729-09-6

• 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: 4-氯-6-(4-(三氟甲基)苯基)嘧啶
• 英文名称: 4-chloro-6-(4-(trifluoromethyl)phenyl)pyrimidine
• 英文别名: 4-chloro-6-[4-(trifluoromethyl)phenyl]pyrimidine
• CAS: 659729-09-6
• 化学式: C₁₁H₆ClF₃N₂
• 分子量: 258.63
• InChiKey: RYYMGPDAXCLXSL-UHFFFAOYSA-N

物化性质

• 沸点：
  318.7±37.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 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：
  25.8
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  4-氯-6-(4-(三氟甲基)苯基)嘧啶 在 potassium fluoride 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 以90%的产率得到4-fluoro-6-(4-(trifluoromethyl)phenyl)pyrimidine
  参考文献：
  名称：

  Novel Vanilloid Receptor-1 Antagonists:  2. Structure−Activity Relationships of 4-Oxopyrimidines Leading to the Selection of a Clinical Candidate

  摘要：

  A series of novel 4-oxopyrimidine TRPV1 antagonists was evaluated in assays measuring the blockade of capsaicin or acid-induced influx of calcium into CHO cells expressing TRPV1. The investigation of the structure-activity relationships in the heterocyclic A-region revealed the optimum pharmacophoric elements required for activity in this series and resulted in the identification of subnanomolar TRPV1 antagonists. The most potent of these antagonists were thoroughly profiled in pharmacokinetic assays. Optimization of the heterocyclic A-region led to the design and synthesis of 23, a compound that potently blocked multiple modes of TRPV1 activation. Compound 23 was shown to be effective in a rodent "on-target" biochemical challenge model (capsaicin-induced flinch, ED50 = 0.33 mg/kg p.o.) and was antihyperalgesic in a model of inflammatory pain (CFA-induced thermal hyperalgesia, MED = 0.83 mg/kg, p.o.). Based on its in vivo efficacy and pharmacokinetic profile, compound 23 (N-{4-[6-(4-trifluoromethyl-phenyl)-pyrimidin-4-yloxy]-benzothiazol-2-yl}-acetamide; AMG 517) was selected for further evaluation in human clinical trials.

  DOI：

  10.1021/jm070190p
• 作为产物：
  描述：

  4,6-二氯嘧啶 、 4-三氟甲基苯硼酸 在 palladium diacetate 、 sodium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 以49%的产率得到4-氯-6-(4-(三氟甲基)苯基)嘧啶
  参考文献：
  名称：

  带有亚磺酰胺基团的新型取代嘧啶衍生物的合成及其体外抑癌活性

  摘要：

  已经描述了两个带有亚磺酰胺基团的新型取代的嘧啶衍生物的合成，并且已经针对三种人类肿瘤细胞系（HT-29，M21和MCF7）评估了它们的体外癌症生长抑制活性。通常，通过在芳香环上引入庞大的取代基来增强生长抑制活性，其中 对于所有人类肿瘤细胞系而言，最佳化合物的GI 50 <6μM。MCF7选择性化合物已在另外4种人类浸润性乳腺导管癌细胞系（MDA-MB-231，MDA-MB-468，SKBR3和T47D）上进行了评估，并且除一种外，在所有情况下均对T47D细胞系具有选择性，表明其潜力抗雌激素活性。

  DOI：

  10.1016/j.bmcl.2016.11.052

文献信息

• [EN] NOVEL HETEROCYCLIC COMPOUNDS AS ANTIMALARIAL AGENTS<br/>[FR] NOUVEAUX COMPOSÉS HÉTÉROCYCLIQUES UTILES EN TANT QU'AGENTS ANTIPALUDIQUES
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2015028989A1

  公开（公告）日：2015-03-05

  The invention relates to novel heterocyclic compounds of the Formula I. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more compounds of the Formula I and especially their use as medicaments to treat or prevent malaria infections or to treat or prevent other protozoal diseases like sleeping sickness, Chagas disease, amebiasis, giardiasis, trichomoniasis, toxoplasmosis, and leishmaniasis.

  本发明涉及式I的新颖杂环化合物。本发明还涉及包括制备化合物的方法、包含式I的一个或多个化合物的药物组合物，尤其是它们作为药物用于治疗或预防疟疾感染或治疗或预防其他原虫疾病，如昏睡病、查加斯病、阿米巴病、贾第虫病、滴虫病、弓形虫病和利什曼病。
• [EN] SUBSTITUTED SULFONAMIDE COMPOUNDS<br/>[FR] COMPOSÉS DE SULFONAMIDE SUBSTITUÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014049047A1

  公开（公告）日：2014-04-03

  The invention is concerned with the compounds of formula (I), and salts thereof, wherein X, Y, Z, R1, R2, R3, R3, R4, R5 and R6 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of Formula (I) as well as pharmaceutical compositions containing such compounds. The compounds may be useful in treating diseases and conditions mediated by TRPA1, such as pain.

  本发明涉及公式(I)的化合物及其盐，其中X、Y、Z、R1、R2、R3、R3、R4、R5和R6在详细描述和权利要求中定义。此外，本发明还涉及制造和使用公式(I)化合物的方法，以及含有此类化合物的药物组合物。这些化合物可能对治疗由TRPA1介导的疾病和状况，如疼痛，有益。
• [EN] PYRIMIDINE COMPOUND AND ITS USE IN PEST CONTROL<br/>[FR] COMPOSÉ PYRIMIDINE ET SON UTILISATION DANS LA LUTTE ANTIPARASITAIRE
  申请人：SUMITOMO CHEMICAL CO

  公开号：WO2010134478A1

  公开（公告）日：2010-11-25

  A pyrimidine compound represented by below formula (I) has excellent control activity against pests and is useful as an active ingredient of a pest controlling agent.

  以下公式（I）所代表的嘧啶化合物对害虫具有出色的控制活性，并可用作杀虫剂的活性成分。
• Vanilloid receptor ligands and their use in treatments
  申请人：Doherty M. Elizabeth

  公开号：US20060241296A1

  公开（公告）日：2006-10-26

  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.

  具有一般结构和成分的化合物及其含量，用于治疗急性、炎症性和神经性疼痛、牙痛、普通头痛、偏头痛、群头痛、混合血管和非血管综合症、紧张性头痛、一般炎症、关节炎、风湿性疾病、骨关节炎、炎性肠道疾病、炎性眼部疾病、炎性或不稳定膀胱疾病、银屑病、带有炎症成分的皮肤疾病、慢性炎症疾病、炎症性疼痛和相关的过敏症和痛觉过敏、神经性疼痛和相关的过敏症和痛觉过敏、糖尿病性神经病疼痛、烧灼性疼痛、交感神经维持性疼痛、去神经综合症、哮喘、上皮组织损伤或功能障碍，单纯疱疹、呼吸、泌尿、消化或血管区域内脏运动障碍、伤口、烧伤、过敏性皮肤反应、瘙痒症、白癜风、一般胃肠道疾病、胃溃疡、十二指肠溃疡、腹泻、由坏死性剂引起的胃病变、头发生长、血管运动或过敏性鼻炎、支气管疾病或膀胱疾病。
• [EN] AMINO-HETEROCYCLES AS VR-1 ANTAGONISTS FOR TREATING PAIN<br/>[FR] HETEROCYCLES AMINES EN TANT QU'ANTAGONISTES DU RECEPTEUR VANILLOIDE (VR-1) POUR LE TRAITEMENT DE LA DOULEUR
  申请人：MERCK SHARP & DOHME

  公开号：WO2004046133A1

  公开（公告）日：2004-06-03

  the present invention provides a compound of formula (I): wherein V represents NR5, O, S, SO or S(O)2; W and X each independently represent CH or N; Y represents N, CH or C-Ar2, with the proviso that at least one, but no more than two, of W, X and Y are N; Z represents CH or C-Ar2, with the proviso that when Y is N or CH then Z is C-Ar2, and with the further proviso that when Y is C-Ar2 then Z is CH; Ar1 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; Ar2 represents an aromatic ring selected from phenyl, pyridyl, pyrimidinyl and pyridazinyl which is optionally fused and substituted; R1 represents halogen, hydroxy, oxo, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, haloC1-6alkyl, hydroxyC1-6alkyl, C1-6alkoxy, haloC1-6alkoxy, hydroxyC1-6alkoxy, C3-7cycloalkyl, C3-7cycloalkoxy, C3-5cycloalkylC1-4alkyl, cyano, nitro, SR6, SOR6, SO2R6, COR6, NR3COR6, CONR3R4, NR3SO2R6, SO2NR3R4, -(CH2)mcarboxy, esterified -(CH2)mcarboxy or -(CH2)mNR3R4; R2 represents hydrogen, halogen, hydroxy, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy, haloC1-6alkoxy, unsubstituted phenyl or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; R3 and R4 are each independently hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl or fluoroC1-6alkyl; or R3 and R4 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 C1-4alkoxy, which ring may optionally contain as one of the said ring atoms an oxygen or a sulfur atom, S(O), S(O)2, or NR5; R5 represents hydrogen, C1-4alkyl, hydroxyC1-4alkyl or C1-4alkoxyC1-4alkyl; R6 represents hydrogen, C1-6alkyl, fluoroC1-6alkyl, C3-7cycloalkyl, unsubstituted phenyl, or phenyl substituted with one or two groups selected from halogen, C1-6alkyl, haloC1-6alkyl, C3-7cycloalkyl, C1-6alkoxy or haloC1-6alkoxy; 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。