7-methoxy-2-(2-thiazolyl)-4-quinolinol | 924289-23-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 7-methoxy-2-(2-thiazolyl)-4-quinolinol
• 英文别名: 4-Hydroxy-7-methoxy-2-(thiazol-2-yl)quinoline；7-methoxy-2-(1,3-thiazol-2-yl)-1H-quinolin-4-one
• CAS: 924289-23-6
• 化学式: C₁₃H₁₀N₂O₂S
• 分子量: 258.301
• InChiKey: ASUXJECESJGLSW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  79.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-methoxy-2-(2-thiazolyl)-4-quinolinol 在 三氯氧磷 作用下， 以95%的产率得到2-(4-chloro-7-methoxyquinolin-2-yl)thiazole
  参考文献：
  名称：

  Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors

  摘要：

  A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (K-i = 0.1 nM, EC50 = 4.5 nM) and selective (CC50 (Huh-7 cells) > 50 mu M) inhibitor, displaying an excellent PK pro. le in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.004
• 作为产物：
  描述：

  N-(2-acetyl-5-methoxyphenyl)-2-thiazolecarboxamide 在 氢氧化钾 作用下， 以 吡啶 为溶剂， 反应 0.5h， 以87%的产率得到7-methoxy-2-(2-thiazolyl)-4-quinolinol
  参考文献：
  名称：

  Macrocyclic Inhibitors of Hepatitis C Virus

  摘要：

  式(I)的化合物：及其N-氧化物、盐和立体异构体，其中A为OR1、NHS(═O)pR2、NHR3、NRaRb、C(═O)NHR3或C(═O)NRaRb，其中；R1为氢、C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基；R2为C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基或NRaRb；R3为C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基、—OC1-C6烷基、—OC0-C3烷基环戊基、—OC0-C3烷基杂环戊基；其中R1、R2或R3中的任何烷基、环戊基或杂环戊基可选择性地被取代；p独立地为1或2；n为3、4、5或6；表示可选的双键；Rq为H或当L为CRz时，Rq也可以是C1-C6烷基；Ry和Ry′独立地为C1-C6烷基；L为N或CRz；Rz为H或与带星号的碳形成双键；W为—CH2—、—O—、—OC(═O)NH—、—OC(═O)—、—S—、—NH—、—NRa、—NHS(═O)2—、—NHC(=0)NH—或—NHC(═O)—、—NHC(═S)NH—或键；R8为含有1或2个饱和、部分饱和或不饱和碳或杂环环的可选择性取代的环系统，在NS-3丝氨酸蛋白酶的抑制中具有用途，例如黄病毒感染。

  公开号：

  US20090023758A1

文献信息

• Macrocyclic Inhibitors of Hepatitis C Virus
  申请人：Wahling Horst

  公开号：US20090023758A1

  公开（公告）日：2009-01-22

  Compounds of the formula (I): and N-oxides, salts and stereoisomers thereof wherein A is OR 1 , NHS(═O) p R 2 , NHR 3 , NRaRb, C(═O)NHR 3 or C(═O)NRaRb wherein; R 1 is hydrogen, C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl; R 2 is C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl or NRaRb; R 3 is C 1 -C 6 alkyl, C 0 -C 3 alkylenecarbocyclyl, C 0 -C 3 alkyleneheterocyclyl, —OC 1 -C 6 alkyl, —OC 0 -C 3 alkylenecarbocyclyl, —OC 0 -C 3 alkyleneheterocyclyl; wherein any alkyl, carbocyclyl or heterocycylyl in R 1 , R 2 or R 3 are optionally substituted p is independently 1 or 2; n is 3, 4, 5 or 6; denotes an optional double bond; Rq is H or when L is CRz, Rq can also be C 1 -C 6 alkyl; Ry and Ry′ are independently C 1 -C 6 alkyl; L is N or CRz; Rz is H or forms a double bond with the asterisked carbon; W is —CH 2 —, —O—, —OC(═O)NH—, —OC(═O)—, —S—, —NH—, —NRa, —NHS(═O) 2 —, —NHC(=0)NH— or —NHC(═O)—, —NHC(═S)NH— or a bond; R 8 is an optionally substituted ring system containing 1 or 2 saturated, partially saturated or unsaturated carbo or heterocyclic rings have utility in the inhibition of NS-3 serine proteases, such as flavivirus infections.

  式(I)的化合物：及其N-氧化物、盐和立体异构体，其中A为OR1、NHS(═O)pR2、NHR3、NRaRb、C(═O)NHR3或C(═O)NRaRb，其中；R1为氢、C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基；R2为C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基或NRaRb；R3为C1-C6烷基、C0-C3烷基环戊基、C0-C3烷基杂环戊基、—OC1-C6烷基、—OC0-C3烷基环戊基、—OC0-C3烷基杂环戊基；其中R1、R2或R3中的任何烷基、环戊基或杂环戊基可选择性地被取代；p独立地为1或2；n为3、4、5或6；表示可选的双键；Rq为H或当L为CRz时，Rq也可以是C1-C6烷基；Ry和Ry′独立地为C1-C6烷基；L为N或CRz；Rz为H或与带星号的碳形成双键；W为—CH2—、—O—、—OC(═O)NH—、—OC(═O)—、—S—、—NH—、—NRa、—NHS(═O)2—、—NHC(=0)NH—或—NHC(═O)—、—NHC(═S)NH—或键；R8为含有1或2个饱和、部分饱和或不饱和碳或杂环环的可选择性取代的环系统，在NS-3丝氨酸蛋白酶的抑制中具有用途，例如黄病毒感染。
• HCV NS-3 serine protease inhibitors
  申请人：Tibotec Pharmaceuticals Ltd.

  公开号：EP1881001A1

  公开（公告）日：2008-01-23

  HCV inhibitors, compositions comprising these compounds as active ingredient, as well as processes for preparing these compounds, having the formula I wherein A is

  HCV抑制剂，包含这些化合物作为活性成分的组合物，以及制备这些化合物的过程，其化学式为I，其中A是。
• Macrocyclic inhibitors of hepatitis C virus
  申请人：Tibotec Pharmaceuticals Ltd.

  公开号：US07989471B2

  公开（公告）日：2011-08-02

  Inhibitors of HCV of formula (I) and the N-oxides, salts, and stereochemically isomeric forms thereof, wherein the terms R1, L, R2, R3, R4, and n have specific definitions; pharmaceutical compositions containing compounds of formula (I), and processes for preparing compounds of formula (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

  公式（I）的HCV抑制剂及其N-氧化物、盐和立体化学异构体，其中术语R1、L、R2、R3、R4和n具有特定定义；含有公式（I）化合物的药物组合物，以及制备公式（I）化合物的过程。还提供了公式（I）的HCV抑制剂与利托那韦的生物利用度组合。
• MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS
  申请人：Simmen Kenneth Alan

  公开号：US20100240698A1

  公开（公告）日：2010-09-23

  Inhibitors of HCV of formula al and the N-oxides, salts, and stereochemically isomeric forms thereof, wherein R 1 is aryl or a saturated, a partially unsaturated or completely unsaturated 5 or 6 membered monocyclic or 8 to 12 membered bicyclic heterocyclic ring system containing one nitrogen, and optionally one to three oxygen, sulfur or nitrogen, wherein said ring system may be optionally substituted; L is a direct bond, —O—, —O—C 1-4 alkanediyl-, —O—CO—, —O—C(═O)—NR 5a — or —O—C(═O)—NR 5a —C 1-4 alkanediyl-; R 2 is hydrogen, —OR 6 , —C(═O)OR 6 , —C(═O)R 7 , —C(═O)NR 5a R 5b , —C(═O)NHR 5c , —NR 5a R 5b , —NHR 5c , —NHSO p NR 5a R 5b , —NR 5a SO p R 8 , or —B(OR 6 ) 2 ; R 3 and R 4 are hydrogen or C 1-6 alkyl; or R 3 and R 4 taken together may form a C 3-7 cycloalkyl ring; n is 3, 4, 5, or 6; p is 1 or 2; aryl is phenyl, naphthyl, indanyl, or 1,2,3,4-tetrahydronaphthyl, each of which may be optionally substituted Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms each independently selected from nitrogen, oxygen and sulfur, being optionally condensed with a benzene ring, and wherein the group Het as a whole may be optionally substituted; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.

  公式aland及其N-氧化物、盐和立体化学同分异构体的HCV抑制剂，其中R1是芳基或饱和、部分不饱和或完全不饱和的5或6元单环或8到12元双环杂环环系统，其中含有一个氮，以及可选的1到3个氧、硫或氮，其中该环系统可以选择性地被取代；L是直接键，-O-，-O-C1-4烷二基，-O-CO-，-O-C（═O）-NR5a-或-O-C（═O）-NR5a-C1-4烷二基；R2是氢、-OR6、-C（═O）OR6、-C（═O）R7、-C（═O）NR5aR5b、-C（═O）NHR5c、-NR5aR5b、-NHR5c、-NHSOpNR5aR5b、-NR5aSOpR8或-B（OR6）2；R3和R4是氢或C1-6烷基；或R3和R4一起可以形成C3-7环烷基；n为3、4、5或6；p为1或2；芳基是苯基、萘基、茚基或1,2,3,4-四氢萘基，每个基团可以选择性地被取代；Het是一个5或6元饱和、部分不饱和或完全不饱和的杂环环，其中每个单独选择的1到4个杂原子分别来自氮、氧和硫，可选择性地与苯环融合，整个Het基团可以选择性地被取代；含有化合物（I）的制药组合物以及制备化合物（I）的过程。还提供了公式（I）的HCV抑制剂与利托那韦的生物利用度组合。
• Discovery of novel potent and selective dipeptide hepatitis C virus NS3/4A serine protease inhibitors
  作者：Pierre Raboisson、Tse-I Lin、Herman de Kock、Sandrine Vendeville、Wim Van de Vreken、David McGowan、Abdellah Tahri、Lili Hu、Oliver Lenz、Frederic Delouvroy、Dominique Surleraux、Piet Wigerinck、Magnus Nilsson、Åsa Rosenquist、Bertil Samuelsson、Kenneth Simmen

  DOI：10.1016/j.bmcl.2008.07.124

  日期：2008.9

  Starting from the previously reported HCV NS3/4A protease inhibitor BILN 2061 (1), we have used a fast-follower approach to identify a novel series of HCV NS3/4A protease inhibitors in which (i) the P3 amino moiety and its capping group have been truncated, (ii) a sulfonamide is introduced in the P1 cyclopropyl amino acid, (iii) the position 8 of the quinoline is substituted with a methyl or halo group, and (iv) the ring size of the macrocycle has been reduced to 14 atoms. SAR analysis performed with a limited set of compounds led to the identification of N-17-[8-chloro-2-(4-isopropylthiazol-2-yl)-7-methoxyquinolin4-yloxy]-2,14-dioxo-3,15-diazatricyclo [13.3.0.0 [Bartenschlager, R.; Lohmann, V. J. Gen. Virol. 2000, 81, 1631; Vincent Soriano, Antonio Madejon, Eugenia Vispo, Pablo Labarga, Javier Garcia-Samaniego, Luz Martin-Carbonero, Julie Sheldon, Marcelle Bottecchia, Paula Tuma, Pablo Barreiro Expert Opin. Emerg. Drugs, 2008, 13, 1-19]]octadec-7-ene-4-carbonyl}(1-methylcyclopropyl)(1-methylcyclopropyl) sulfonamide 19l an extremely potent (K-i = 0.20 nM, EC50 = 3.7 nM), selective, and orally bioavailable dipeptide NS3/4A protease inhibitor, which has features attractive for further preclinical development. (C) 2008 Elsevier Ltd. All rights reserved.