2-hydroxy-4-(thien-3-ylmethoxy)benzonitrile | 170282-49-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-hydroxy-4-(thien-3-ylmethoxy)benzonitrile
• 英文别名: 2-hydroxy-4-(thien-3-yl)methoxybenxonitrile；2-Hydroxy-4-(3-thienylmethoxy)benzonitrile；2-hydroxy-4-(thiophen-3-ylmethoxy)benzonitrile
• CAS: 170282-49-2
• 化学式: C₁₂H₉NO₂S
• 分子量: 231.275
• InChiKey: KXSMXHHXTJWILO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  81.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-hydroxy-4-(thien-3-ylmethoxy)benzonitrile 在 sodium hydroxide 、 sodium hydride 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.17h， 生成 (RS)-[2-cyano-5-(thien-3-ylmethoxy)phenoxy]-phenylacetic acid
  参考文献：
  名称：

  Selective ET_A Antagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives

  摘要：

  The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ETA receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ETA antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC50 59 nM, rat aortic ETA). Optimization of 13a led to the identification of 27b, which exhibited an IC50 of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 mu mol/kg) and was duly proposed and accepted as a development candidate.

  DOI：

  10.1021/jm990378b
• 作为产物：
  描述：

  2-hydroxy-4-(thien-3-yl)methoxybenzaldehyde oxime 在 甲醇 、 sodium acetate 、 potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 2-hydroxy-4-(thien-3-ylmethoxy)benzonitrile
  参考文献：
  名称：

  Selective ET_A Antagonists. 5. Discovery and Structure−Activity Relationships of Phenoxyphenylacetic Acid Derivatives

  摘要：

  The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ETA receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ETA antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC50 59 nM, rat aortic ETA). Optimization of 13a led to the identification of 27b, which exhibited an IC50 of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 mu mol/kg) and was duly proposed and accepted as a development candidate.

  DOI：

  10.1021/jm990378b

文献信息

• Substituted phenyl compounds with a substituent having a thienyl ring
  申请人：Rhone-Poulenc Rorer Limited

  公开号：US06124343A1

  公开（公告）日：2000-09-26

  This invention is directed to compounds of formula I ##STR1## wherein R.sup.1 is CN, CH.sub.2 CN, CH.dbd.CHCN, CHO, or CH.dbd.CHCO.sub.2 H; R.sup.2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio wherein each of the aryl and heteroaryl moieties is optionally substituted; R.sup.3 is halogen; R.sup.4 is optionally substituted aryl or optionally substituted heteroaryl; R.sup.5 is carboxy or an acid isostere; X is oxygen or sulphur; and n is zero or 1; or an N-oxide thereof, prodrug thereof solvate thereof, or pharmaceutically acceptable salt thereof, which compounds have endothelin antagonist activity. The invention is also directed to methods for preparing the compounds of formula I and their pharmaceutical use.

  这项发明涉及式I的化合物##STR1##其中R.sup.1为CN、CH.sub.2CN、CH.dbd.CHCN、CHO或CH.dbd.CHCO.sub.2H；R.sup.2为芳基低烷氧基、杂芳基低烷氧基、芳基低烷硫基或杂芳基低烷硫基，其中芳基和杂芳基中的每一个可选择地被取代；R.sup.3为卤素；R.sup.4为可选择地被取代的芳基或可选择地被取代的杂芳基；R.sup.5为羧基或酸异构体；X为氧或硫；n为零或1；或其N-氧化物、前药、溶剂化合物或药学上可接受的盐，这些化合物具有内皮素拮抗活性。该发明还涉及制备式I化合物及其药用的方法。
• Substituted phenyl compounds
  申请人：Rhone-Poulenc Rorer Limited

  公开号：US06211234B1

  公开（公告）日：2001-04-03

  Compounds of formula (I) are described wherein R1 is hydrogen, -(lower alkyl)q(CO2R6 or OH), —CN, —C(R7)═NOR8, NO2, —O(lower alkyl)R9, —C≡C—R10, —CR11═C(R12)(R13), —C(═O)CH2C(═O)CO2H, —CO(R14), alkylthio, alkylsulphinyl, alkylsulphonyl, carbamoyl, thiocarbamoyl, substituted carbamoyl, substituted thiocarbamoyl, sulphamoyl or an optionally substituted nitrogen-containing ring, m, n, o and p are independently zero or 1 and R2, R3, R4 and R5 are various groups; and physiologically acceptable salts, N-oxides and prodrugs thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.

  式(I)的化合物描述如下，其中R1为氢，-(较低烷基)q(CO2R6或OH)，—CN，—C(R7)HNOR8，NO2，—O(较低烷基)R9，—C≡C—R10，—CR11CH(R12)(R13)，—C(O)CH2C(O)CO2H，—CO(R14)，烷基硫醚，烷基亚砜基，烷基磺酰基，氨基甲酰基，硫代氨基甲酰基，取代的氨基甲酰基，取代的硫代氨基甲酰基，磺酰胺基或可选择取代的含氮环，m、n、o和p独立地为零或1，R2、R3、R4和R5为各种基团；以及其生理学上可接受的盐、N-氧化物和前药。这些化合物具有内皮素拮抗活性，并可用作药物。
• [EN] SUBSTITUTED PHENYL COMPOUNDS AS ENDOTHELIN ANTAGONISTS<br/>[FR] COMPOSES PHENYLES SUBSTITUES UTILISES COMME ANTAGONISTES DE L'ENDOTHELINE
  申请人：RHONE POULENC RORER LIMITED

  公开号：WO1996022978A1

  公开（公告）日：1996-08-01

  (EN) Compounds of formula (I) are described, wherein: R1 is CN, CH2CN, CH=CHCN, CHO, or CH=CHCO2H; R2 is aryl lower alkoxy, heteroaryl lower alkoxy, aryl lower alkylthio or heteroaryl lower alkylthio in which each of the aryl and heteroaryl moieties is optionally substituted; R3 is halogen; R4 is optionally substituted aryl or optionally substituted heteroaryl; R5 is carboxy or an acid isostere; X is oxygen or sulphur; and n is zero or 1; and their N-oxides and prodrugs, and pharmaceutically acceptable salts thereof. The compounds have endothelin antagonist activity and are useful as pharmaceuticals.(FR) L'invention porte sur des composés de la formule (I), leurs oxydes d'azote, leurs précurseurs de médicament ainsi que les sels acceptables du point de vue pharmaceutique qui en sont issus. Dans cette formule, R1 est CN, CH2CN, CH=CHCN, CHO, ou CH=CHCO2H; R2 est aryle alcoxy inférieur, hétéroaryle alcoxy inférieur, aryle alkylthio inférieur ou hétéroaryle alkylthio inférieur, dans lequel chacun des fragments aryle ou hétéroaryle peut, éventuellement, être substitué; R3 est halogène; R4 est éventuellement aryle substitué ou hétéroaryle substitué; R5 est carboxy ou un isostère acide; X est oxygène ou soufre et n vaut zéro ou 1. Ces composés, qui ont une activité antagoniste de celle de l'endothéline, ont montré leur efficacité en tant que préparations pharmaceutiques

  化合物的公式（I）被描述，其中：R1为CN，CH2CN，CH=CHCN，CHO或CH=CHCO2H; R2为芳基低烷氧基，杂芳基低烷氧基，芳基低烷硫基或杂芳基低烷硫基，其中每个芳基和杂芳基可以选择性地被取代; R3为卤素; R4为可选择性取代的芳基或可选择性取代的杂芳基; R5为羧基或酸异构体; X为氧或硫; n为零或1; 以及它们的N-氧化物和前药，以及药学上可接受的盐。这些化合物具有内皮素拮抗剂活性，可用作制药用途。
• US6048893
  申请人：——

  公开号：——

  公开（公告）日：——
• SUBSTITUTED PHENYL COMPOUNDS
  申请人：RHONE-POULENC RORER LIMITED

  公开号：EP0728128B1

  公开（公告）日：1998-09-16