Methyl 3-(3-Cyclopentyloxy-4-methoxyphenyl)benzoate | 159612-90-5

• 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: Methyl 3-(3-Cyclopentyloxy-4-methoxyphenyl)benzoate
• 英文别名: 3'-Cyclopentyloxy-4'-methoxy-biphenyl-3-carboxylic acid methyl ester
• CAS: 159612-90-5
• 化学式: C₂₀H₂₂O₄
• 分子量: 326.392
• InChiKey: NTPZVZAPVCZKMA-UHFFFAOYSA-N

物化性质

• 沸点：
  462.459±40.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.144±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 3-(3-Cyclopentyloxy-4-methoxyphenyl)benzoate 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 3'-Cyclopentyloxy-4'-methoxy-biphenyl-3-carboxylic acid
  参考文献：
  名称：

  Biarylcarboxylic Acids and -amides:  Inhibition of Phosphodiesterase Type IV versus [³H]Rolipram Binding Activity and Their Relationship to Emetic Behavior in the Ferret

  摘要：

  In addition to having desirable inhibitory effects on inflammation, anaphylaxis, and smooth muscle contraction, PDE-IV inhibitors also produce undesirable side effects including nausea and vomiting. In general, compounds that inhibit PDE-IV also potently displace [H-3]rolipram from a high-affinity binding site in rat cortex.(1,2) While this binding site has not been identified, it has been proposed to be an allosteric binding site on the PDE-IV enzyme.(3) Preliminary studies have suggested that the emetic potency of PDE-IV inhibitors is correlated with affinity for the brain rolipram binding site rather than potency at inhibiting PDE-IV enzyme activity. Efforts to eliminate the emetic potential of PDE-IV inhibitors were directed toward developing compounds with decreased [H-3]rolipram binding affinity while retaining PDE-IV potency. Thus, a novel series of 4-(3-alkoxy-4-methoxyphenyl)benzoic acids and their corresponding carboxamides were prepared and evaluated for their PDE-IV inhibitory and rolipram binding site properties. Modification of the catechol ether moiety led to phenylbutoxy and phenylpentoxy analogues that provided the desired actitivity profile. Specifically, 4-[3-(5-phenylpentoxy)-4-methoxyphenyl]-2-methylbenzoic acid, 18, was found to exhibit potent PDE-IV inhibitory activity (IC50 0.41 mu M) and possessed 400 times weaker activity than rolipram for the [H-3]rolipram binding site. In vivo, compound 18 was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED(50) 8.8 mg/kg, po) and demonstrated a significant reduction in emetic side effects (ferret, 20% emesis at 30 mg/kg, po).

  DOI：

  10.1021/jm9505066
• 作为产物：
  描述：

  5-溴-2-甲氧基苯酚 在 四(三苯基膦)钯 、 正丁基锂 、 三苯基膦 、 zinc(II) chloride 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 Methyl 3-(3-Cyclopentyloxy-4-methoxyphenyl)benzoate
  参考文献：
  名称：

  Biarylcarboxylic Acids and -amides:  Inhibition of Phosphodiesterase Type IV versus [³H]Rolipram Binding Activity and Their Relationship to Emetic Behavior in the Ferret

  摘要：

  In addition to having desirable inhibitory effects on inflammation, anaphylaxis, and smooth muscle contraction, PDE-IV inhibitors also produce undesirable side effects including nausea and vomiting. In general, compounds that inhibit PDE-IV also potently displace [H-3]rolipram from a high-affinity binding site in rat cortex.(1,2) While this binding site has not been identified, it has been proposed to be an allosteric binding site on the PDE-IV enzyme.(3) Preliminary studies have suggested that the emetic potency of PDE-IV inhibitors is correlated with affinity for the brain rolipram binding site rather than potency at inhibiting PDE-IV enzyme activity. Efforts to eliminate the emetic potential of PDE-IV inhibitors were directed toward developing compounds with decreased [H-3]rolipram binding affinity while retaining PDE-IV potency. Thus, a novel series of 4-(3-alkoxy-4-methoxyphenyl)benzoic acids and their corresponding carboxamides were prepared and evaluated for their PDE-IV inhibitory and rolipram binding site properties. Modification of the catechol ether moiety led to phenylbutoxy and phenylpentoxy analogues that provided the desired actitivity profile. Specifically, 4-[3-(5-phenylpentoxy)-4-methoxyphenyl]-2-methylbenzoic acid, 18, was found to exhibit potent PDE-IV inhibitory activity (IC50 0.41 mu M) and possessed 400 times weaker activity than rolipram for the [H-3]rolipram binding site. In vivo, compound 18 was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED(50) 8.8 mg/kg, po) and demonstrated a significant reduction in emetic side effects (ferret, 20% emesis at 30 mg/kg, po).

  DOI：

  10.1021/jm9505066

文献信息

• Substituted biphenyl derivatives
  申请人：American Home Products Corporation

  公开号：US05691376A1

  公开（公告）日：1997-11-25

  A compound of the following structure: ##STR1## wherein R.sub.8 =H: R.sub.1 =alkyl, cycloalkyl, arylalkyl, aryl; R.sub.2 =cycloalkyl, aryl, C.sub.3 -C.sub.10 alkyl; X,Y=O, S(O).sub.n, NH; Z=CO.sub.2 R.sub.3, C(O)CO.sub.2 R.sub.3, CH(OH)CO.sub.2 R.sub.3, CHFCO.sub.2 R.sub.3, CF.sub.2 CO.sub.2 R.sub.3, CONR.sub.3 R.sub.4, CONR.sub.3 OR.sub.4, CONR.sub.3 NR.sub.4 R.sub.5, 1-tetrazole, C(O)CONR.sub.3 R.sub.4, CH(OH)CONR.sub.3 R.sub.4, CF.sub.2 CONR.sub.3 R.sub.4 R.sub.3, R.sub.4, R.sub.5 =hydrogen, alkyl, aryl, aryalkyl, cycloalkyl, or fluoroalkyl; halo=Cl, Br, or I; fluoroalkyl=CF.sub.3, CHF.sub.2, CH.sub.2 F, CH.sub.2 CF.sub.3, C.sub.2 F.sub.5 ; cycloalkyl=C.sub.3 -C.sub.6 cycloalkyl; arylalkyl=C.sub.1 -C.sub.4 alkyl aryl; aryl=phenyl, furanyl, thienyl, or pyridyl; and n=0-2; or pharmaceutically acceptable salts thereof, useful in the treatment of asthma, and allergic and inflammatory diseases, as well as methods of treatment and pharmaceutical compositions utilizing the same.

  以下为结构式：##STR1## 其中 R.sub.8 =H: R.sub.1 =烷基，环烷基，芳基烷基，芳基; R.sub.2 =环烷基，芳基，C.sub.3 -C.sub.10 烷基; X，Y=O，S(O).sub.n，NH; Z=CO.sub.2 R.sub.3，C(O)CO.sub.2 R.sub.3，CH(OH)CO.sub.2 R.sub.3，CHFCO.sub.2 R.sub.3，CF.sub.2 CO.sub.2 R.sub.3，CONR.sub.3 R.sub.4，CONR.sub.3 OR.sub.4，CONR.sub.3 NR.sub.4 R.sub.5，1-四唑，C(O)CONR.sub.3 R.sub.4，CH(OH)CONR.sub.3 R.sub.4，CF.sub.2 CONR.sub.3 R.sub.4 R.sub.3，R.sub.4，R.sub.5 =氢，烷基，芳基，芳基烷基，环烷基或氟烷基; 卤素=Cl，Br或I; 氟烷基=CF.sub.3，CHF.sub.2，CH.sub.2 F，CH.sub.2 CF.sub.3，C.sub.2 F.sub.5 ; 环烷基=C.sub.3 -C.sub.6 环烷基; 芳基烷基=C.sub.1 -C.sub.4 烷基芳基; 芳基=苯基，呋喃基，噻吩基或吡啶基; n=0-2; 或其药学上可接受的盐，用于治疗哮喘，过敏和炎症性疾病，以及使用相同的治疗方法和制药组合物。
• TRI-SUBSTITUTED PHENYL DERIVATIVES AND PROCESSES FOR THEIR PREPARATION
  申请人：CELLTECH THERAPEUTICS LIMITED

  公开号：EP0618889B1

  公开（公告）日：1998-12-30
• SUBSTITUTED BIPHENYL DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0745063B1

  公开（公告）日：1999-03-24
• US5491147A
  申请人：——

  公开号：US5491147A

  公开（公告）日：1996-02-13
• US5650444A
  申请人：——

  公开号：US5650444A

  公开（公告）日：1997-07-22