3'-Cyclopentyloxy-4'-methoxy-biphenyl-3-carboxylic acid | 158427-68-0

• 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'-Cyclopentyloxy-4'-methoxy-biphenyl-3-carboxylic acid
• 英文别名: 3-(3-Cyclopentyloxy-4-methoxyphenyl)benzoic acid
• CAS: 158427-68-0
• 化学式: C₁₉H₂₀O₄
• 分子量: 312.365
• InChiKey: SQUXYQGSZSUWDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3'-Cyclopentyloxy-4'-methoxy-biphenyl-3-carboxylic acid 、 三甲基硅烷化重氮甲烷 以 四氢呋喃 、 甲醇 、 正己烷 、 乙酸乙酯 为溶剂， 以150 mg (79%)的产率得到Methyl 3-(3-Cyclopentyloxy-4-methoxyphenyl)benzoate
  参考文献：
  名称：

  Substituted biphenyl derivatives

  摘要：

  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。

  公开号：

  US05691376A1
• 作为产物：
  描述：

  4-溴-2-(环戊基氧基)苯甲醚 在 sodium hydroxide 、 四(三苯基膦)钯 、 正丁基锂 、 zinc(II) chloride 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

文献信息

• SUBSTITUTED BIPHENYL DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0745063A1

  公开（公告）日：1996-12-04
• US5650444A
  申请人：——

  公开号：US5650444A

  公开（公告）日：1997-07-22
• US5691376A
  申请人：——

  公开号：US5691376A

  公开（公告）日：1997-11-25
• [EN] SUBTITUTED BIPHENYL TNF INHIBITORS<br/>[FR] INHIBITEURS DU FACTEUR DE NECROSE TUMORALE A SUBSTITUTION BIPHENYLE
  申请人：SMITHKLINE BEECHAM CORPORATION

  公开号：WO1995027692A1

  公开（公告）日：1995-10-19

  (EN) Novel compounds for formula (I) are described herein. These compounds inhibit the production of Tumor Necrosis Factor and are useful in the treatment of disease states mediated or exacerbated by TNF production; these compounds are also useful in the mediation or inhibition of enzymatic or catalytic activity of phosphodiesterase IV.(FR) L'invention se rapporte à de nouveaux composés de la formule (I). Ces composés inhibent la formation du facteur de nécrose tumorale et sont utilisés dans le traitement d'états pathologiques induits ou exacerbés par la formation du facteur de nécrose tumorale; ces composés sont également utiles dans la médiation ou l'inhibition de l'activité enzymtatique ou catalytique de la phosphodiestérase IV.
• [EN] SUBSTITUTED BIPHENYL DERIVATIVES AS PHOSPHODIESTERASE INHIBITORS<br/>[FR] DERIVES BIPHENYLE SUBSTITUES UTILISES COMME INHIBITEURS DE LA PHOSPHODIESTERASE
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：WO1995022520A1

  公开（公告）日：1995-08-24

  (EN) A compound of structure (I), wherein, when R8 = H: R1 = alkyl, cycloalkyl, arylalkyl, aryl; R2 = cycloalkyl, aryl, C3-C10 alkyl; X, Y = O, S(O)n, NH; Z = CH2OH, NHSO2R3, CHO, CO2R3, CONHR4R5, CN, COR6, H, halo, NHCN, NHCONR4R5, CONR4OR5, CONR4NR5R6, 1-tetrazole, S(O)nOH, S(O)nNR3R4, C=NOH, C(=N(OH)NH2, OCONR7R6, P(O)(OR4)2, NH2, SH, OH, OS(O)2R3, C(O)CO2R3, C(O)CONR3R4, CH(OH)CO2R3, CHFCO2R3, CF2CO2R3, CH(OH)CONR3R4, CF2CONR3R4, C=NNH2, C(=NOC(=O)R3)R4, C(=NNHC(=O)R3)R4, C(=NOH)R3, C(=NNR3)R4, NHC(=O)R6 or C(O)CONH2; R3, R4, R5, R6, R7 = hydrogen, alkyl, aryl, aryalkyl, cycloalkyl, or fluoroalkyl; or a compound of Structure I, wherein: R1 = alkyl, cycloalkyl, aryalkyl, or aryl; R2 = cycloalkyl, aryl, or alkyl; X, Y = CH2, O, S(O)n), or NH; R3, R4, R5, R6, R7 are each, independently, hydrogen, alkyl, aryl, aryalkyl, cycloalkyl, or fluoroalkyl; R8 = CO2R3, CONR3, or R8 and Z are concatenated such that R8Z = C(O)NHNHC(O), (CH2)mC(=W), V(CH2)mC(=W), or VnCH=CH(CH2)nC(=W); where V = O, S(O)n, NH; W = O, NOH, NHNH2, NOC(O)CH3, or NNHC(O)CH3; halo = Cl, Br, or I; fluoroalkyl = CF3CHF2, CH2F, CH2CF3, C2F5; cycloalkyl = C3-C6 cycloalkyl; aryalkyl = C1-C4 aryl; aryl = phenyl, furanyl, thienyl, or pyridyl; n = 0-2; and m = 2-4 or pharmaceutically acceptable salts thereof, useful in the treatment of asthma, or allergic or inflammatory diseases, as well as methods of treatment and pharmaceutical compositions utilizing the same.(FR) L'invention concerne un composé ayant la formule (I). Dans cette fomule, lorsque R8 = H, R1 = alkyle, cycloalkyle, arylalkyle, aryle; R2 = cycloalkyle, aryle, C3-C10 alkyle; X, Y = O, S(O)n, NH; Z = CH2OH, NHSO2R3, CHO, CO2R3, CONHR4R5, CN, COR6, H, halo, NHCN, NHCONR4R5, CONR4OR5, CONR4NR5R6, 1-tétrazole, S(O)nOH, S(O)nNR3R4, C=NOH, C(=N(OH)NH2, OCONR7R6, P(O)(OR4)2, NH2, SH, OH, OS(O)2R3, C(O)CO2R3, C(O)CONR3R4, CH(OH)CO2R3, CHFCO2R3, CF2CO2R3, CH(OH)CONR3R4, CF2CONR3R4, C=NNH2, C(=NOC(=O)R3)R4, C(=NNHC(=O)R3)R4, C(=NOH)R3, C(=NNR3)R4, NHC(=O)R6 or C(O)CONH2; R3, R4, R5, R6, R7 = hydrogène, alkyle, aryle, aryalkyle, cycloalkyle, ou fluoroalkyle; ou un composé de la formule (I), où R1 = alkyle, cycloalkyle, aryalkyle, or aryle; R2 = cycloalkyle, aryle, ou alkyle; X, Y = CH2, O, S(O)n), ou NH; R3, R4, R5, R6, R7 sont chacun d'une manière indépendante un hydrogène, alkyle, aryle, aryalkyle, cycloalkyle, ou fluoroalkyle; R8 = CO2R3, CONR3, ou R8 et Z sont reliés pour que R8Z = C(O)NHNHC(O), (CH2)mC(=W), V(CH2)mC(=W); ou VnCH=CH(CH2)nC(=W); où V = O, S(O)n, NH; W = O, NOH, NHNH2, NOC(O)CH3, ou NNHC(O)CH3; halo = Cl, Br, or I; fluoroalkyle = CF3CHF2, CH2F, CH2CF3, C2F5; cycloalkyle = C3-C6 cycloalkyle; aryalkyle = C1-C4 aryle; aryle = phényle, furanyle, thiényle, or pyridyle; n = 0-2; et m = 2-4. L'invention concerne également les sels de ces composés, acceptables sur le plan pharmaceutique. Ces produits sont utiles pour le traitement de l'asthme, d'allergies ou de maladies inflammatoires. L'invention concerne également des compositions pharmaceutiques contenant ces produits et leur utilisation.