3-(trifluoromethylthio)benzoyl chloride | 51748-28-8

• 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-(trifluoromethylthio)benzoyl chloride
• 英文别名: 3-trifluoromethylthio-benzoyl chloride；3-trifluoromethylthiobenzoyl chloride；3-(trifluoromethylsulfanyl)benzoyl chloride
• CAS: 51748-28-8
• 化学式: C₈H₄ClF₃OS
• 分子量: 240.633
• InChiKey: UACYHAIRBPOIBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 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：
  42.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-(trifluoromethylthio)benzoyl chloride 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 12.5h， 生成 (5-Methoxy-1H-indol-2-yl)-(3-trifluoromethylsulfanyl-phenyl)-methanone
  参考文献：
  名称：

  Synthetic 2-Aroylindole Derivatives as a New Class of Potent Tubulin-Inhibitory, Antimitotic Agents

  摘要：

  A new class of simple synthetic antimitotic compounds based on 2-aroylindoles was discovered. (5-Methoxy-1H-2-indolyl)-phenylmethanone (1) as well as analogous 3-fluorophenyl- (36) and 3-methoxyphenyl (3) derivatives displayed high cytotoxicity Of IC50 = 20 to 75 nM against the human HeLa/KB cervical, SK-OV-3 ovarian, and U373 astrocytoma carcinoma cell lines. The inhibition of proliferation correlated with the arrest in the G2/M phase of the cell cycle. In in vitro assays with tubulin isolated from bovine brain, in general antiproliferative activity correlated with inhibition of tubulin polymerization. Thus, the antimitotic activity of 2-aroylindoles is explained by interference with the mitotic spindle apparatus and destabilization of microtubules. In contrast to colchicine, vincristine, nocodazole, or taxol, I did not significantly affect the GTPase activity of beta -tubulin. Interestingly, selected compounds inhibited angiogenesis in the chorioallantoic membrane (CAM) assay. In xenograft experiments, 1 was highly active after oral administration at 200 mg/kg against the human amelanocytic melanoma MEXF 989 in athymic nude mice. We conclude, that 2-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.

  DOI：

  10.1021/jm010940+
• 作为产物：
  描述：

  3-(三氟甲基硫代)溴苯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 草酰氯 、 水 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 3-(trifluoromethylthio)benzoyl chloride
  参考文献：
  名称：

  [EN] FUSED AZOLE AND FURAN BASED NUCLEOSIDE ANALOGS AND USES THEREOF
  [FR] ANALOGUES DE NUCLÉOSIDES À BASE D'AZOLE ET DE FURANE FUSIONNÉS ET LEURS UTILISATIONS

  摘要：

  The present invention is directed to compounds and compositions comprising thereof. Further, methods of use such as for the treatment and prevention of cancer and other diseases responsive to the inhibition of UAE and/or UBA6 in a subject in need thereof are also provided.

  公开号：

  WO2023021498A1

文献信息

• 3,4-DIHYDRO-2H-BENZO[1,4]OXAZINE AND THIAZINE DERIVATIVES AS CETP INHIBITORS
  申请人：Kuo Gee-Hong

  公开号：US20070265252A1

  公开（公告）日：2007-11-15

  The invention is directed to compounds of Formula (I) described herein useful as CETP inhibitors, compositions containing them, and methods of using them.

  本发明涉及式(I)化合物，所述化合物作为CETP抑制剂是有用的，包含它们的组合物以及使用它们的方法。
• IMIDAZO[4, 5-B]PYRIDIN-2-ONE AND OXAZOLO[4, 5-B]PYRIDIN-2-ONE COMPOUNDS AND ANALOGS THEREOF AS CANCER THERAPEUTIC COMPOUNDS
  申请人：Niculescu-Duvaz Dan

  公开号：US20090325945A1

  公开（公告）日：2009-12-31

  The present invention pertains to certain imidazo[4,5-b]pyridin-2-one and oxazolo[4,5 b]pyridin-2-one compounds and analogs thereof, which, inter alia, inhibit RAF (e.g., B RAF) activity, inhibit cell proliferation, treat cancer, etc., and more particularly to compounds of the formulae: wherein: J is independently —O— or —NR N1− ; R N1 , if present, is independently —H or a substituent; R N2 is independently —H or a substituent; Y is independently —CH═ or —N═; Q is independently —(CH 2 ) j -M-(CH 2 ) k — wherein: j is independently 0, 1 or 2; k is independently 0, 1, or 2; j+k is 0, 1, or 2; M is independently O—, —S—, —NH—, —NMe-, or —CH 2 —; each of R P1 , R P2 , R P5 , and R P4 is independently —H or a substituent; and additionally R P1 and R P2 taken together may be CH═CH—CH═CH—; and additionally R P1 and R P5 taken together may be CH═CH—CH═CH—; L is independently: a linker group formed by a chain of 2, 3, or 4 linker moieties; each linker moiety is independently CH 2 —, —NR N —, —C(═X)—, or —S(═O) 2 —; either: exactly one linker moiety is —NR N —, or: exactly two linker moieties are —NR N —; either: exactly one linker moiety is —C(═X)—, and no linker moiety is —S(═O) 2 —, or: exactly one linker moiety is —S(═O) 2 —, and no linker moiety is —C(═X)—; no two adjacent linker moieties are —NR N —; X is independently ═O or ═S; each R N is independently —H or a substituent; A is independently: C 6-14 carboaryl, C 5-14 heteroaryl, C 3-12 carbocyclic, C 3-12 heterocyclic; and is independently unsubstituted or substituted; and pharmaceutically acceptable salts, solvates, amides, esters, ethers, N-oxides, chemically protected forms, and prodrugs thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., B-RAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and conditions that are ameliorated by the inhibition of RAF, RTK, etc., proliferative conditions such as cancer (e.g., colorectal cancer, melanoma), etc.

  本发明涉及特定的咪唑并[4,5-b]吡啶-2-酮和噁唑并[4,5-b]吡啶-2-酮化合物及其类似物，其中，它们可以抑制RAF（例如B-RAF）活性，抑制细胞增殖，治疗癌症等。特别是本发明涉及以下式的化合物：其中：J独立地为—O—或—NRN1−；RN1（如果存在）独立地为—H或取代基；RN2独立地为—H或取代基；Y独立地为—CH═或—N═；Q独立地为—（CH2）j-M-（CH2）k—，其中：j独立地为0、1或2；k独立地为0、1或2；j+k为0、1或2；M独立地为O—、—S—、—NH—、—NMe-或—CH2—；RP1、RP2、RP5和RP4中的每一个独立地为—H或取代基；并且另外RP1和RP2一起可以是CH═CH—CH═CH—；并且另外RP1和RP5一起可以是CH═CH—CH═CH—；L独立地为：由2、3或4个连接基成的连接基团；每个连接基单元独立地为CH2—、—NRN—、—C（═X）—或—S（═O）2—；要么：恰好有一个连接基单元为—NRN—，或：恰好有两个连接基单元为—NRN—；要么：恰好有一个连接基单元为—C（═X）—，且没有连接基单元为—S（═O）2—，或：恰好有一个连接基单元为—S（═O）2—，且没有连接基单元为—C（═X）—；没有两个相邻的连接基单元为—NRN—；X独立地为═O或═S；每个RN独立地为—H或取代基；A独立地为：C6-14碳基芳基、C5-14杂环芳基、C3-12环烷基、C3-12杂环烷基；并且独立地未取代或取代；以及其药学上可接受的盐、溶剂化合物、酰胺、酯、醚、N-氧化物、化学保护形式和前药。本发明还涉及包含这样的化合物的药物组合物，以及这样的化合物和组合物的使用，无论是在体外还是在体内，来抑制RAF（例如B-RAF）活性，抑制受体酪氨酸激酶（RTK）活性，抑制细胞增殖，并治疗通过抑制RAF、RTK等而改善的疾病和情况，如癌症（例如结肠癌、黑色素瘤）等。
• PHENYLAMINOPYRIMIDINE DERIVATIVES AS INHIBITORS OF BCR-ABL KINASE
  申请人：KOMPELLA Amala Kishan

  公开号：US20080306100A1

  公开（公告）日：2008-12-11

  The present invention relates to novel intermediates useful for the preparation of novel phenylaminopyrimidine derivatives, novel phenylaminopyrimidine derivatives. Pharmaceutical composition containing the novel phenylaminopyrimidine derivatives and processes for their preparation. The invention particularly relates to novel Phenyl pyrimidine amine derivatives of the general formula (I). The novel compounds of the formula 1 can be used in the therapy of Chronic Myeloid Leukemia (CML). Since the IC 50 ; 191 values of these molecules are in the range 0.1 to 10.0 nm, these novel compounds are potentially useful for the treatment of CML. The present invention relates to a particular form of the (3,5-bis trifluoromethyl)-N-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide (formula I), processes for the preparation thereof, pharmaceutical compositions containing this crystal form, and their use as anti tumor agent in humans. The compound of formula I, also known as AN-019, is: This invention relates to a process for the preparation of (3-trifluoromethylsulfonyl)-N-[4-methyl-3-(4-pyridin-3yl-pyrimidin-2ylamino)-phenyl]-benzamide (formula (I)) starting from 4-methyl-2-nitro-aniline (formula (II)) through intermediates (3-trifluoromethylsulfonyl)-N-[4-methyl-3-nitrophenyl]-benzamide (formula (III)), (3-trifluoromethylsulfonyl)-N-[3-amino-4-methylphenyl]-benzamide (formula (IV)) and (3-trifluoromethylsulfonyl)-N-[ 3 -guanidino- 4 -methylphenyl]-benzamide (formula (V)). This invention also relates to processes for the preparation of these intermediates. The compound of formula (I), also known as AN-024, is:

  本发明涉及用于制备新的苯基氨基嘧啶衍生物的新中间体，新的苯基氨基嘧啶衍生物，含有这些新的苯基氨基嘧啶衍生物的制药组合物以及它们的制备过程。本发明特别涉及一般式（I）的新苯基嘧啶胺衍生物。公式1的新化合物可用于慢性髓细胞白血病（CML）的治疗。由于这些分子的IC50; 191值在0.1至10.0纳米的范围内，这些新化合物有潜在的用于治疗CML的作用。本发明涉及一种特定形式的（3,5-双三氟甲基）-N- [4-甲基-3-（4-吡啶-3-基-嘧啶-2-基氨基）-苯基] -苯甲酰胺（公式I），其制备过程，含有该晶体形式的制药组合物，以及它们在人体内作为抗肿瘤剂的用途。公式I的化合物，也称为AN-019，是：本发明涉及一种从4-甲基-2-硝基苯胺（公式（II））通过中间体（3-三氟甲基磺酰基）-N- [4-甲基-3-硝基苯基] -苯甲酰胺（公式（III）），（3-三氟甲基磺酰基）-N- [3-氨基-4-甲基苯基] -苯甲酰胺（公式（IV））和（3-三氟甲基磺酰基）-N- [3-胍基-4-甲基苯基] -苯甲酰胺（公式（V））开始制备（3-三氟甲基磺酰基）-N- [4-甲基-3-（4-吡啶-3-基-嘧啶-2-基氨基）-苯基] -苯甲酰胺（公式（I））的过程。本发明还涉及制备这些中间体的过程。公式（I）的化合物，也称为AN-024，是：
• Substituierte 2,2-Dimethylpentan (en)-1-carbonsäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung zur Herstellung von Styrylcyclopropancarbonsäuren
  申请人：BAYER AG

  公开号：EP0018531A1

  公开（公告）日：1980-11-12

  Die vorliegende Erfindung betrifft ein neues Verfahren zur Herstellung von Styryl-cyclopropan-carbonsäureestern der allgemeinen Formel (I) in welcher R bis R2 die in der Beschreibung angegebene Bedeutung besitzen, das dadurch gekennzeichnet ist, daß man Verbindungen der allgemeinen Formel (II) (Verfahren 1a), (III) (Verfahren 1b) oder (IV) (Verfahren 1c)

  本发明涉及一种制备通式(I)苯乙烯基环丙烷羧酸酯的新工艺 其中 R 至 R2 具有说明中给出的含义，其特征在于通式 (II)（工艺 1a）、(III)（工艺 1b）或 (IV) （工艺 1c）的化合物
• Novel Potent BRAF Inhibitors: Toward 1 nM Compounds through Optimization of the Central Phenyl Ring
  作者：Delphine Ménard、Ion Niculescu-Duvaz、Harmen P. Dijkstra、Dan Niculescu-Duvaz、Bart M. J. M. Suijkerbuijk、Alfonso Zambon、Arnaud Nourry、Esteban Roman、Lawrence Davies、Helen A. Manne、Frank Friedlos、Ruth Kirk、Steven Whittaker、Adrian Gill、Richard D. Taylor、Richard Marais、Caroline J. Springer

  DOI：10.1021/jm900242c

  日期：2009.7.9

  BRAF, a serine/threonine specific protein kinase that is part of the MAPK pathway and acts as a downstream effector of RAS, is a potential therapeutic target in melanoma. We have developed a series of small-molecule BRAF inhibitors based on a 1H-imidazo[4,5-b]pyridine-2(3H)-one scaffold (ring A) as the hinge binding moiety and a number Of Substituted phenyl rings C that interact with the allosteric binding site. The introduction of various groups on the central phenyl ring B combined with appropriate A- and C-ring modifications afford very potent compounds that inhibit (V600E)BRAF kinase activity in vitro and oncogqnic BRAF signaling in melanoma cells. Substitution on the central phenyl ring of a 3-fluoro, a naphthyl, or a 3-thiomethyl group improves activity to yield compounds with an IC50 of 1 nM for purified (V600E)BRAF and nanomolar activity in cells.