2-chloro-6-fluoro-4-iodoaniline | 702640-40-2

• 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: 2-chloro-6-fluoro-4-iodoaniline
• 英文别名: 2-Fluoro-4-iodo-6-chloroaniline
• CAS: 702640-40-2
• 化学式: C₆H₄ClFIN
• 分子量: 271.46
• InChiKey: MBOVEKLHHKYVAH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-6-fluoro-4-iodoaniline 在 potassium phosphate 、 palladium 10% on activated carbon 、 四丁基溴化铵 、 sodium acetate 、 palladium diacetate 、 三(邻甲基苯基)磷 、 2-二环己膦基-2'-(N,N-二甲胺)-联苯 作用下， 以 N,N-二甲基乙酰胺 、 正丁醇 为溶剂， 反应 24.0h， 生成 trans-4-((4-((2-chloro-4-(2-cyanovinyl)-6-fluorophenyl)amino)-6-fluoroquinazoline-2-yl)amino)benzonitrile
  参考文献：
  名称：

  Molecular Hybridization-Inspired Optimization of Diarylbenzopyrimidines as HIV-1 Nonnucleoside Reverse Transcriptase Inhibitors with Improved Activity against K103N and E138K Mutants and Pharmacokinetic Profiles

  摘要：

  Molecular hybridization is a powerful strategy in drug discovery. A series of novel diarylbenzopyrimidine (DABP) analogues were developed by the hybridization of FDA-approved drugs etravirine (ETR) and efavirenz (EFV) as potential HIV-1 nonnudeoside reverse transcriptase inhibitors (NNRTIs). Substituent modifications resulted in the identification of new DABPs with the combination of the strengths of the two drugs, especially compound lid, which showed promising activity toward the EFV-resistant K103N mutant. 12d also had a favorable pharmacokinetic (PK) profile with liver microsome clearances of 14.4 mu L/min/mg (human) and 33.2 mu L/min/mg (rat) and an oral bioavailability of 15.5% in rat. However, its activity against the E138K mutant was still unsatisfactory; E138K is the most prevalent NNRTI resistance-associated mutant in ETR treatment Further optimizations resulted in a highly potent compound (12z) with no substituents on the phenyl ring and a 2-methyl-6-nitro substitution pattern on the 4-cyanovinyl-2,6-disubstitued phenyl motif. The antiviral activity of this compound was much higher than those of ETR and EFV against the WT, E138K, and K103N variants (EC50 = 3.4, 4.3, and 3.6 nM, respectively), and the cytotoxicity was decreased while the selectivity index (SI) was increased. In particular, this compound exhibited acceptable intrinsic liver microsome stability (human, 34.5 mu L/min/mg; rat, 33.2 mu L/min/mg) and maintained the good PK profile of its parent compound EFV and showed an oral bioavailability of 16.5% in rat. Molecular docking and structure-activity relationship (SAR) analysis provided further insights into the binding of the DABPs with HIV-1 reverse transcriptase and provided a deeper understanding of the key structural features responsible for their interactions.

  DOI：

  10.1021/acsinfecdis.9b00229
• 作为产物：
  描述：

  2-氯-6-氟苯胺 在 N-碘代丁二酰亚胺 作用下， 以 乙腈 为溶剂， 生成 2-chloro-6-fluoro-4-iodoaniline
  参考文献：
  名称：

  用于靶向癌症治疗的可见光控制的组蛋白脱乙酰酶抑制剂

  摘要：

  抗癌药物缺乏选择性限制了目前的化疗。光激活药物的活性可以通过外部光精确控制，可以使药物在肿瘤中发挥更局部的作用，从而减少副作用并提高疗效。在此，我们介绍了一系列光开关偶氮苯组蛋白脱乙酰酶抑制剂 (HDACis)，其活性可通过外部可见光控制。最初的 HDACis 在紫外光下异构化，在酶测定中，光照下的活性比黑暗中高 50 倍以上。然后通过引入o将这些化合物优化为对更具渗透性和危害性更小的绿光作出反应的化合物-卤素原子变成偶氮苯。选定的化合物仅在四种不同癌细胞系的光照下降低细胞活力。总的来说，我们提出了具有优化激活波长的光开关 HDACis，它仅在用可见光照射时才抑制酶活性和细胞活力，这有助于光开关抗癌药物的工具箱仍然有限。

  DOI：

  10.1021/acs.jmedchem.2c01713

文献信息

• [EN] ETHYNYL DERIVATIVES<br/>[FR] DÉRIVÉS D'ÉTHYNYLE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017021384A1

  公开（公告）日：2017-02-09

  The present invention relates to compounds of formula (I) wherein R1 is hydrogen, F or CI; L is a bond or lower alkylene; R2 is -(CH2)nO-lower alkyl, lower alkyl substituted by halogen, -(CH2)nC(0)0-lower alkyl, phenyl substituted by lower alkyl or halogen, or is a 5 or 6-membered heteroaryl group, selected from pyridinyl, pyrimidinyl, pyridazinyl, thiazolyl, imidazolyl, pyrazolyl or triazolyl, which are optionally substituted by lower alkyl, halogen, lower alkoxy, =0, benzyloxy, cycloalkyloxy, hydroxy, cyano, lower alkyl substituted by halogen, or by -(CH2)nO-lower alkyl; n is 1, 2 or 3; R3 is hydrogen, lower alkyl or -(CH2)nO-lower alkyl; R4 is phenyl, pyridinyl or pyrimidinyl, optionally substituted by F; Y is CF or CCl; or to a pharmaceutically acceptable salt or acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomers thereof. The compounds may be used for the treatment of Parkinson's disease, anxiety, emesis, obsessive compulsive disorder, autism, neuroprotection, cancer, depression and diabetes type 2.

  本发明涉及以下式(I)的化合物，其中R1是氢、F或Cl；L是键或较低的烷基；R2是-(CH2)nO-较低烷基、受卤素取代的较低烷基、-( )nC(0)0-较低烷基、受较低烷基或卤素取代的苯基、或是5或6-成员杂环芳基，选自吡啶基、嘧啶基、吡啉基、噻唑基、咪唑基、吡唑基或三唑基，可以选择地受较低烷基、卤素、较低烷氧基、=0、苄氧基、环烷氧基、羟基、氰基、受卤素取代的较低烷基、或者是-( )nO-较低烷基取代；n为1、2或3；R3是氢、较低烷基或-( )nO-较低烷基；R4是苯基、吡啶基或嘧啶基，可以选择地受F取代；Y是CF或CCl；或者是其药学上可接受的盐或酸加合盐，或者是外消旋混合物，或者是其对映体和/或光学异构体和/或立体异构体。这些化合物可用于治疗帕金森病、焦虑、呕吐、强迫症、自闭症、神经保护、癌症、抑郁症和2型糖尿病。
• [EN] SUBSTITUTED AMINO PHENYLACETIC ACIDS, DERIVATIVES THEREOF, THEIR PREPARATION AND THEIR USE AS CYCLOOXYGENASE 2 (COX-2) INHIBITORS<br/>[FR] ACIDES AMINO PHENYLACETIQUES SUBSTITUES, DERIVES DE CEUX-CI, PROCEDE POUR LES PREPARER ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE CYCLOOXYGENASE 2 (COX-2)
  申请人：NOVARTIS AG

  公开号：WO2004048314A1

  公开（公告）日：2004-06-10

  Compounds of formula (I) wherein R is hydrogen, lower alkyl, (C3-C8)cycloalkyl, hydroxy, halo, lower alkoxy, trifluoromethoxy, trifluoromethyl or cyano; and A is biaryl, optionally substituted β-naphthyl, bicyclic heterocyclic aryl, (C3-C6)cycloalkylmonocyclic carbocyclic aryl, or (C5 or C6)cycloalkane fused-monocyclic carbocyclic aryl; pharmaceutically acceptable salts thereof, and pharmaceutically acceptable esters thereof; which are useful for the treatment of COX-2 dependent disorders.

  式(I)中R为氢、较低的烷基、(C3-C8)环烷基、羟基、卤素、较低的烷氧基、三氟甲氧基、三氟甲基或氰基；A为联苯、可选择地取代的β-萘基、双环杂环芳基、(C3-C6)环烷基单环碳环芳基，或(C5或C6)环烷烃融合的单环碳环芳基；其药学上可接受的盐，以及其药学上可接受的酯；用于治疗COX-2依赖性疾病。
• [EN] PYRROLOPYRIDAZINE COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS DE PYRROLOPYRIDAZINE UTILISÉS COMME INHIBITEURS DE KINASE
  申请人：GOSSAMER BIOSERVICES INC

  公开号：WO2022109492A1

  公开（公告）日：2022-05-27

  Described herein are inhibitors of JAK kinases, pharmaceutical compositions comprising them, processes for preparing them and uses of such inhibitors to treat or prevent diseases, disorders and conditions associated with kinase function.

  本文描述了JAK激酶抑制剂，包括它们的制药组合物、制备它们的过程以及使用这些抑制剂来治疗或预防与激酶功能相关的疾病、紊乱和病况。
• Certain phenylacetic acids and derivatives
  申请人：——

  公开号：US20040132769A1

  公开（公告）日：2004-07-08

  Compounds of formula (I) 1 wherein R is hydrogen, lower alkyl, (C 3 -C 6 )cycloalkyl, hydroxy, halo, lower alkoxy, trifluoromethoxy, trifluoromethyl or cyano; and A is biaryl, optionally substituted &bgr;-naphthyl, bicyclic heterocyclic aryl, (C 3 -C 6 )cycloalkylmonocyclic carbocyclic aryl, or (C 5 or C 6 )cycloalkane fused-monocyclic carbocyclic aryl; pharmaceutically acceptable salts thereof; and pharmaceutically acceptable esters thereof; which are useful for the treatment of COX-2 dependent disorders.

  化学式为(I)1的化合物，其中R为氢、低碳基、(C3-C6)环烷基、羟基、卤素、低烷氧基、三氟甲氧基、三氟甲基或氰基；而A为双芳基、可选取代的β-萘基、双环杂环芳基、(C3-C6)环烷基单环碳环芳基，或(C5或C6)环烷基融合的单环碳环芳基；其药学上可接受的盐和酯，可用于治疗COX-2依赖性疾病。
• Ethynyl derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US10011607B2

  公开（公告）日：2018-07-03

  The present invention relates to compounds of formula I wherein R1 is hydrogen, F or Cl; L is a bond or lower alkylene; R2 is —(CH2)nO-lower alkyl, lower alkyl substituted by halogen, —(CH2)nC(O)O-lower alkyl, phenyl substituted by lower alkyl or halogen, or is a 5 or 6-membered heteroaryl group, selected from pyridinyl, pyrimidinyl, pyridazinyl, thiazolyl, imidazolyl, pyrazolyl or triazolyl, which are optionally substituted by lower alkyl, halogen, lower alkoxy, ═O, benzyloxy, cycloalkyloxy, hydroxy, cyano, lower alkyl substituted by halogen, or by —(CH2)nO-lower alkyl; n is 1, 2 or 3; R3 is hydrogen, lower alkyl or —(CH2)nO-lower alkyl; R4 is phenyl, pyridinyl or pyrimidinyl, optionally substituted by F; Y is CF or CCl; or to a pharmaceutically acceptable salt or acid addition salt, to a racemic mixture, or to its corresponding enantiomer and/or optical isomer and/or stereoisomers thereof. The compounds may be used for the treatment of Parkinson's disease, anxiety, emesis, obsessive compulsive disorder, autism, neuroprotection, cancer, depression and diabetes type 2.

  本发明涉及式 I 的化合物 式中 R1 是氢、F 或 Cl L 是键或低级亚烷基 R2 是-(CH2)nO-低级烷基、被卤素取代的低级烷基、-( )nC(O)O-低级烷基、被低级烷基或卤素取代的苯基，或者是选自吡啶基、嘧啶基、哒嗪基、噻唑基、咪唑基、吡唑基或三唑基的 5 或 6 元杂芳基、噻唑基、咪唑基、吡唑基或三唑基，它们可任选被低级烷基、卤素、低级烷氧基、═O、苄氧基、环烷氧基、羟基、氰基、被卤素取代的低级烷基或被-( )nO-低级烷基取代； n 是 1、2 或 3； R3 是氢、低级烷基或-( )nO-低级烷基； R4 是苯基、吡啶基或嘧啶基，可选择被 F 取代； Y 是 CF 或 CCl； 或药学上可接受的盐或酸加成盐、外消旋混合物或其相应的对映体和/或光学异构体和/或立体异构体。 这些化合物可用于治疗帕金森病、焦虑症、呕吐、强迫症、自闭症、神经保护、癌症、抑郁症和 2 型糖尿病。