丙硫丙咪唑 | 55225-86-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 中文名称: 丙硫丙咪唑
• 中文别名: 丙硫苯咪胺酯；丙巯咪唑；阿丙条；丙硫达唑；间三氟甲氧基异氰酸酯；阿苯哒唑
• 英文名称: 1-isocyanato-3-(trifluoromethoxy)benzene
• 英文别名: 3-trifluoromethoxyphenyl isocyanate；3-(Trifluoromethoxy)phenyl isocyanate
• CAS: 55225-86-0
• 化学式: C₈H₄F₃NO₂
• 分子量: 203.12
• InChiKey: OKJYBJOTWLVTAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-氨基-4-氯-6-甲基嘧啶 、 丙硫丙咪唑 以 甲苯 为溶剂， 反应 7.0h， 以15%的产率得到1-(4-chloro-6-methylpyrimidin-2-yl)-3-(3-(trifluoromethoxy)phenyl)urea
  参考文献：
  名称：

  [EN] INHIBITION OF OLIG2 ACTIVITY
  [FR] INHIBITION DE L'ACTIVITÉ D'OLIG2

  摘要：

  本文描述了含有这些化合物的化合物和药物组合物，这些化合物抑制Olig2的活性。本文还描述了使用这些Olig2抑制剂的方法，单独或与其他化合物结合，用于治疗癌症和其他疾病。特别是Olig2抑制剂可用于治疗胶质母细胞瘤。

  公开号：

  WO2016138479A1
• 作为产物：
  描述：

  三光气 、 3-三氟甲氧基苯胺 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 丙硫丙咪唑
  参考文献：
  名称：

  Structure–Activity Relationship Studies of Pyrazolo[3,4-d]pyrimidine Derivatives Leading to the Discovery of a Novel Multikinase Inhibitor That Potently Inhibits FLT3 and VEGFR2 and Evaluation of Its Activity against Acute Myeloid Leukemia in Vitro and in Vivo

  摘要：

  We describe the structural optimization of a hit compound, 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-ylamino)phenyl)-3-(3-methoxyphenyl)urea (1), which exhibits inhibitory activity but low potency against FLT3 and VEGFR2. A series of pyrazolo [3,4-d]pyrimidine derivatives were synthesized, and structure-activity relationship analysis using cell- and transgenic-zebrafish-based assays led to the discovery of a number of compounds that exhibited both high potency against FLT3-driven human acute myeloid leukemia (AML) MV4-11 cells and a considerable antiangiogenic effect in transgenic-zebrafish-based assays. The compound 1-(4-(1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)phenyl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea (33), which exhibited the highest activity in preliminary in vivo anti-AML assays, was chosen for further anti AML studies. The results demonstrated that compound 33 is a multikinase inhibitor that potently inhibits FLT3 and VEGFR2. In an MV4-11 xenograft mouse model, a once daily dose of compound 33 at 10 mg/kg for 18 days led to complete tumor regression without obvious toxicity. Western blot and immunohistochemical analyses were performed to determine the mechanism of action of compound 33.

  DOI：

  10.1021/jm301537p

文献信息

• [EN] ISOINDOLINONE COMPOUNDS<br/>[FR] COMPOSÉS D'ISO-INDOLINONE
  申请人：MONTE ROSA THERAPEUTICS

  公开号：WO2021069705A1

  公开（公告）日：2021-04-15

  Disclosed herein is a compound or pharmaceutically acceptable salts or stereoisomers thereof of of formula I wherein X1 is linear or branched C1-6 alkyl, C3-6 cycloalkyl, -C1-6 alkyl C3-6 cycloalkyl, C6-10 aryl, 5-10 membered heteroaryl, C1-6 alkyl C6-10 aryl, C1-6 alkyl 5-10 membered heteroaryl, wherein X1 is unsubstituted or substituted with one or more of halogen, linear or branched C1-6 alkyl, linear or branched C1-6 heteroalkyl, CF3, CHF2, -O-CHF2, -O-(CH2)2-OMe, OCF3, C1-6 alkylamino, -CN, -N(H)C(O)-C1- 6alkyl, -OC(O)-C1-6alkyl, -OC(O)-C1-4alkylamino, -C(O)O-C1-6alkyl, -COOH, - CHO, -C1-6alkylC(O)OH, -C1-6alkylC(O)O-C1-6alkyl, NH2, C1-6 alkoxy or C1-6 alkylhydroxy; X2 is hydrogen, C6-10 aryl, 5-10 membered heteroaryl, -O-(5-10 membered heteroaryl), 4-8 membered heterocycloalkyl, C1-4 alkyl 4-8 membered heterocycloalkyl, -O-(4-8 membered heterocycloalkyl), -O-C1-4 alkyl-(4-8 membered heterocycloalkyl), -OC(O)-C1-4alkyl-4-8 membered heterocycloalkyl or C6 aryloxy, wherein X2 is unsubstituted or substituted with one or more of linear or branched C1-6 alkyl, NH2, NMe2 or 5-6 membered heterocycloalkyl; n is 0, 1 or 2.

  本公开涉及一种化合物或药用可接受盐或其立体异构体，其化学式为I，其中X1为直链或支链的C1-6烷基，C3-6环烷基，-C1-6烷基C3-6环烷基，C6-10芳基，5-10成员杂芳基，C1-6烷基C6-10芳基，C1-6烷基5-10成员杂芳基，其中X1未取代或取代为一个或多个卤素，直链或支链的C1-6烷基，直链或支链的C1-6杂烷基，CF3，CHF2，-O- ，-O-(CH2)2-OMe，O ，C1-6烷基氨基，-CN，-N(H)C(O)-C1-6烷基，-OC(O)-C1-6烷基，-OC(O)-C1-4烷基氨基，-C(O)O-C1-6烷基，-COOH，-CHO，-C1-6烷基C(O)OH，-C1-6烷基C(O)O-C1-6烷基，NH2，C1-6烷氧基或C1-6烷基羟基；X2为氢，C6-10芳基，5-10成员杂芳基，-O-(5-10成员杂芳基)，4-8成员杂环烷基，C1-4烷基4-8成员杂环烷基，-O-(4-8成员杂环烷基)，-O-C1-4烷基-(4-8成员杂环烷基)，-OC(O)-C1-4烷基-4-8成员杂环烷基或C6芳氧基，其中X2未取代或取代为一个或多个直链或支链的C1-6烷基，NH2，NMe2或5-6成员杂环烷基；n为0、1或2。
• NOVEL HETEROCYCLYL COMPOUNDS
  申请人：Aebi Johannes

  公开号：US20110092698A1

  公开（公告）日：2011-04-21

  The invention is concerned with novel bicyclic compounds of formula (I), wherein n, m, p, A, L, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 7 , R 8 , R 9 , and R 10 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds are antagonists of CCR2 receptor, CCR5 receptor and/or CCR3 receptor may be used, for example, in the prevention and/or treatment of inflammatory diseases, particularly peripheral arterial occlusive diseases or atherothrombosis.

  这项发明涉及式(I)的新颖双环化合物，其中n、m、p、A、L、R1、R2、R3、R4、R5、R6、R7、R7、R8、R9和R10如描述和索赔中所定义，并且其生理上可接受的盐。这些化合物是CCR2受体、CCR5受体和/或CCR3受体的拮抗剂，例如可用于预防和/或治疗炎症性疾病，特别是外周动脉闭塞疾病或动脉粥样硬化形成。
• [EN] DIAZEPAM DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTORS<br/>[FR] DÉRIVÉS DU DIAZÉPAM EN TANT QUE MODULATEURS DES RÉCEPTEURS DES CHIMIOKINES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2011048032A1

  公开（公告）日：2011-04-28

  The invention is concerned with novel bicyclic compounds of Formula (I), wherein n, m, p, A, L, R1, R2, R3, R4, R5, R6, R7, R7, R8, R9 and R10 are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds are antagonists of CCR2 receptor, CCR5 receptor and/or CCR3 receptor and can be used as medicaments.

  这项发明涉及公式（I）的新颖双环化合物，其中n、m、p、A、L、R1、R2、R3、R4、R5、R6、R7、R7、R8、R9和R10的定义如描述和索赔中所述，以及其生理上可接受的盐。这些化合物是CCR2受体、CCR5受体和/或CCR3受体的拮抗剂，可用作药物。
• [EN] INHIBITORS OF CYTOKININ OXIDASE DERIVED FROM 1-[2-(HYDROXYALKYL)PHENYL]-3-YLUREA, USE THEREOF AND PREPARATIONS CONTAINING THESE DERIVATIVES<br/>[FR] INHIBITEURS DE LA CYTOKININE OXYDASE DÉRIVÉS DE 1-[2-(HYDROXYALKYL)PHÉNYL]-3-YL-URÉE, LEUR UTILISATION ET PRÉPARATIONS CONTENANT CES DÉRIVÉS
  申请人：UNIV PALACKEHO

  公开号：WO2021185391A1

  公开（公告）日：2021-09-23

  The present invention relates to substituted 1-[2-(hydroxyalkyl)phenyl]-3-yl-urea derivatives of the general formula (I), which inhibit one of the key plant enzymes cytokinin oxidase/dehydrogenase (CKX); wherein R1 is hydrogen, halogen, methoxy group, trifluoromethoxy group, methylsulphanyl group or trifluoromethylsulphanyl group; R2 is hydrogen, halogen, amino group, (C1-C5) alkyl, (C2-C5) alkenyl, (C2-C5) alkynyl, or (C1-C5) alkylamino group, wherein (C1-C5) alkyl, (C2-C5) alkenyl, (C2-C5) alkynyl and (C-C5) alkylamino group is optionally substituted with hydroxy and/or amino group; and R3 and R4 are independently hydrogen or halogen, and wherein when X is nitrogen, then R2 is hydrogen or halogen. The invention further relates to the use of these substances in agriculture as stimulators of plant growth and development and as anti-stress factors and to the preparations containing these derivatives.

  本发明涉及通式（I）的取代1-[2-(羟基烷基)苯基]-3-基脲衍生物，其抑制植物关键酶细胞分裂素氧化酶/脱氢酶（CKX）之一；其中R1为氢、卤素、甲氧基、三氟甲氧基、甲基硫基或三氟甲基硫基；R2为氢、卤素、氨基、（C1-C5）烷基、（C2-C5）烯基、（C2-C5）炔基或（C1-C5）烷基氨基，其中（C1-C5）烷基、（C2-C5）烯基、（C2-C5）炔基和（C-C5）烷基氨基可以选择性地与羟基和/或氨基取代；R3和R4独立地为氢或卤素，当X为氮时，R2为氢或卤素。本发明还涉及这些物质在农业中作为植物生长和发育的刺激剂以及抗压因子的使用，以及含有这些衍生物的制剂。
• Structure activity relationship (SAR) study identifies a quinoxaline urea analog that modulates IKKβ phosphorylation for pancreatic cancer therapy
  作者：Satish Sagar、Sarbjit Singh、Jayapal Reddy Mallareddy、Yogesh A. Sonawane、John V. Napoleon、Sandeep Rana、Jacob I. Contreras、Christabelle Rajesh、Edward L. Ezell、Smitha Kizhake、Jered C. Garrison、Prakash Radhakrishnan、Amarnath Natarajan

  DOI：10.1016/j.ejmech.2021.113579

  日期：2021.10

  conducted structure activity relationship (SAR) study to improve potency and oral bioavailability of a quinoxaline analog 13–197 that was previously reported as a NFκB inhibitor for pancreatic cancer therapy. The SAR led to the identification of a novel quinoxaline urea analog 84 that reduced the levels of p-IKKβ in dose- and time-dependent studies. When compared to 13–197, analog 84 was ∼2.5-fold more

  遗传模型验证了核因子 (NF) κ B 激酶β (IKKβ) 抑制剂作为 KRAS 突变相关胰腺癌的治疗靶点。IKKβ中激活环丝氨酸残基（S 177，S 181）的磷酸化是驱动肿瘤坏死因子（TNF）α诱导的NF-κB介导的基因表达的关键事件。在这里，我们进行了结构活性关系 (SAR) 研究，以提高喹喔啉类似物 13-197 的效力和口服生物利用度，该类似物先前被报道为胰腺癌治疗的 NFκB 抑制剂。SAR 导致发现了一种新的喹喔啉尿素类似物84，它在剂量和时间依赖性研究中降低了 p-IKKβ 的水平。与 13–197 相比，模拟84对 TNFα 诱导的 NFκB 抑制作用强 2.5 倍，抑制胰腺癌细胞生长的作用强 4 倍。模拟84的暴露量增加了 4.3 倍（AUC 0-∞) 与 13-197 相比，导致口服生物利用度 (%F) 增加约 5.7 倍。重要的是，在异种移植模型中，单独口服84和与吉西他滨联合使用可降低