4-[2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-hydroxyethyl]pyridine | 159088-38-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-[2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-hydroxyethyl]pyridine
• 英文别名: 1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(pyrid-4-yl)ethanol；(+/-)-4-[2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-hydroxyethyl]pyridine；(+/-)-1-(3-cyclopentyloxy-4-methoxyphenyl)-2-(pyrid-4-yl)ethanol；1-(3-cyclopentyloxy-4-methoxyphenyl)-2-pyridin-4-ylethanol
• CAS: 159088-38-7
• 化学式: C₁₉H₂₃NO₃
• 分子量: 313.397
• InChiKey: OEPSQXZPZXNBDU-UHFFFAOYSA-N

物化性质

• 沸点：
  467.405±45.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.173±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  51.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-hydroxyethyl]pyridine 在 bis(triphenylphosphine)nickel(II) chloride 、 甲烷磺酸 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 16.25h， 生成 4-[2-(3-Cyclopentyloxy-4-methoxyphenyl)but-3-enyl]pyridine
  参考文献：
  名称：

  Ni-catalyzed nucleophilic conjugate additions of Grignard and organozincate reagents to substituted 4-vinylpyridines. General synthesis of phosphodiesterase IV inhibitors

  摘要：

  Alkyl, aryl, and vinyl Grignard reagents were added to olefin II under Ni(acac)(2) or Cl2Ni(PPh3)(2) catalysis to give products with the general formula I in 74-95% yield. Organozincates gave similar results with Ni(acac), as the catalyst, (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(97)10217-4
• 作为产物：
  描述：

  4-甲基吡啶 、 3-环戊氧-4-甲氧基苯甲醛 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 4-[2-(3-Cyclopentyloxy-4-methoxyphenyl)-2-hydroxyethyl]pyridine
  参考文献：
  名称：

  Ni-catalyzed nucleophilic conjugate additions of Grignard and organozincate reagents to substituted 4-vinylpyridines. General synthesis of phosphodiesterase IV inhibitors

  摘要：

  Alkyl, aryl, and vinyl Grignard reagents were added to olefin II under Ni(acac)(2) or Cl2Ni(PPh3)(2) catalysis to give products with the general formula I in 74-95% yield. Organozincates gave similar results with Ni(acac), as the catalyst, (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(97)10217-4

文献信息

• Compounds containing phenyl linked to aryl or heteroaryl by an
  申请人：Rhone-Poulenc Rorer Limited

  公开号：US05935978A1

  公开（公告）日：1999-08-10

  This invention is directed to the pharmaceutical use of phenyl compounds, which are linked to an aryl moiety by various linkages, for inhibiting tumor necrosis factor. The invention is also directed to the compounds, their preparation and pharmaceutical compositions containing these compounds. Furthermore, this invention is directed to the pharmaceutical use of the compounds for inhibiting cyclic AMP phosphodiesterase.

  这项发明涉及苯基化合物的药用，这些化合物通过各种连接与芳基团相连，用于抑制肿瘤坏死因子。该发明还涉及这些化合物、它们的制备以及含有这些化合物的药物组合物。此外，这项发明还涉及这些化合物的药用，用于抑制环磷酸腺苷磷酸二酯酶。
• [EN] SUBSTITUTED AROMATIC COMPOUNDS AS c.AMP PHOSPHODIESTERASE- AND TNF-INHIBITORS<br/>[FR] COMPOSES AROMATIQUES SUBSTITUES EN TANT QU'INHIBITEURS DE LA c.AMP PHOSPHODIESTERASE ET DU FNT
  申请人：RHONE-POULENC RORER LIMITED

  公开号：WO1995020578A1

  公开（公告）日：1995-08-03

  (EN) This invention is directed to compounds of formula (I), wherein R1 is an optionally substituted lower alkyl group; R2 is an optionally substituted oxaaliphatic group; R3 is an optionally substituted aryl group or an optionally substituted heteroaryl group; Q1, Q2 and Q3 are independently nitrogen, CX or CH; Z1 is oxygen or sulfur; Z2 is -CH=CH-, -C$m(Z)C-, -CH2-CZ-, -CZCH2-, -CZ-CZ-, -CH2-NH-, -CH2-O-, -CH2-S-, -CX2-O-, -CZNH-, -NH-CH2-, -O-CH2_, -SCH2-, -SOCH2-, -SO2CH2-, -O-CX2-, -O-CZ-, -NH-CZ-, -N=N-, -NH-SO2-, -SO2-NH-, -CZ-CZ-NH-, -NH-CO-O-, -O-CO-NH- or -NH-CO-NH-; Z is oxygen or sulfur; and X is halo; or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which possess useful pharmaceutical properties. They are especially useful for inhibiting the production or physiological effects of TNF and inhibit cyclic AMP. The present invention is also directed to their pharmaceutical use, pharmaceutical compositions containing the compounds, and methods for their preparation.(FR) La présente invention a pour objet des composés de la formule (I), dans laquelle R1 représente un groupe alcoyle inférieur avec substitution éventuelle; R2 représente un groupe oxa-aliphatique avec substitution éventuelle; R3 représente un groupe aryle avec substitution éventuelle ou un groupe hétéroaryle avec substitution éventuelle; Q1, Q2 et Q3 représentent, indépendamment, de l'azote, CX ou CH; Z1 représente de l'oxygène ou du soufre; Z2 représente -CH=CH-, -C$m(Z)C, -CH2-CZ-, -CZCH2-, -CZ-CZ-, -CH2-NH-, -CH2-O-, -CH2-S-, -CX2-O-, -CZNH-, -NH-CH2-, -O-CH2-, -SCH2-, SOCH2-, -SO2CH2-, -O-CX2-, -O-CZ-, -NH-CZ-, -N=N-, -NH-SO2-, -SO2-NH-, -CZ-CZ-NH-, -NH-CO-O-, -O-CO-NH- ou -NH-CO-NH-; Z représente de l'hydrogène ou du soufre; et X représente halo, ou un N-oxyde de celui-ci ou un sel pharmaceutiquement acceptable de celui-ci, qui possède des propriétés pharmaceutiques utiles. Ces composés sont particulièrement utiles pour inhiber la production ou les effets physiologiques du FNT et inhiber l'AMP cyclique. La présente invention concerne également l'utilisation pharmaceutique de ces composés, des compositions pharmaceutiques qui les contiennent et des procédés pour leur préparation.

  该发明涉及化合物(I)的公式，其中R1是可选择取代的低碳基；R2是可选择取代的氧杂脂肪基；R3是可选择取代的芳基或可选择取代的杂芳基；Q1、Q2和Q3独立地是氮、CX或CH；Z1是氧或硫；Z2是-CH=CH-、-C$m(Z)C-、-CH2-CZ-、-CZCH2-、-CZ-CZ-、-CH2-NH-、-CH2-O-、-CH2-S-、-CX2-O-、-CZNH-、-NH-CH2-、-O-CH2_、-SCH2-、-SOCH2-、-SO2CH2-、-O-CX2-、-O-CZ-、-NH-CZ-、-N=N-、-NH-SO2-、-SO2-NH-、-CZ-CZ-NH-、-NH-CO-O-、-O-CO-NH-或-NH-CO-NH-；Z是氧或硫；X是卤素；或其N-氧化物或药学上可接受的盐，具有有用的药物特性。它们特别适用于抑制TNF的产生或生理效应并抑制环磷酸腺苷。本发明还涉及它们的药物用途，含有该化合物的药物组合物以及其制备方法。
• Compounds as PDE IV and TNF-inhibitors
  申请人：Fenton Garry

  公开号：US20060084809A1

  公开（公告）日：2006-04-20

  This invention is directed to a [di(ether or thioether)heteroaryl or fluoro substituted aryl] compound or an N-oxide thereof or a pharmaceutically acceptable salt thereof, which is useful for inhibiting the production or physiological effects of TNF in the treatment of a patient suffering from a disease state associated with a physiologically detrimental excess of tumor necrosis factor (TNF). Compounds within the scope of the present invention also inhibit cyclic AMP phosphodiesterase, and are useful in treating a disease state associated with pathological conditions that are modulated by inhibiting cyclic AMP phosphodiesterase, such disease states including inflammatory and autoimmune diseases, in particular type IV cyclic AMP phosphodiesterase. The present invention is therefore directed to their pharmacological use for inhibiting TNF and/or cyclic AMP phosphodiesterase, pharmacological compositions comprising the compounds and methods for their preparation.

  本发明涉及[含有(di(醚或硫醚)杂环或氟代芳基)化合物]或其N-氧化物或其药学上可接受的盐，该化合物在治疗患有与肿瘤坏死因子（TNF）生产或生理作用过量有害相关的疾病状态的患者中有用，能够抑制TNF的产生或生理作用。本发明范围内的化合物还抑制环磷酸腺苷磷酸二酯酶，并且在治疗与抑制环磷酸腺苷磷酸二酯酶相关的病理条件的疾病状态中有用，这些疾病状态包括炎症和自身免疫性疾病，特别是第四型环磷酸腺苷磷酸二酯酶。因此，本发明涉及它们在抑制TNF和/或环磷酸腺苷磷酸二酯酶方面的药理学用途，包括含有这些化合物的药理学组合物以及它们的制备方法。
• Tetra-substituted phenyl derivatives and processes for their preparation
  申请人：——

  公开号：US20010034450A1

  公开（公告）日：2001-10-25

  Compounds of general formula (1): 1 are described wherein ═W— is (1) ═C(Y)— where Y is a halogen atom, or an alkyl, or -X a R 1 group where X a is —O—, —S(O) m — [where m is zero or an integer of value 1 or 2], or N(R a )- [where R a is a hydrogen atom or an optionally substituted alkyl group] and R 1 is a hydrogen atom or an optionally substituted alkyl group or, (2) ═N—; X is as described above for X a or is a chain —CR═C(R b )— or [—CH(R)] q —CH(R b )- where R is a hydrogen or a fluorine atom or a methyl group, R b is as described below for R 2 and q is zero or the integer 1; R 2 is (1) an optionally substituted alkyl, alkenyl, cycloalkyl or cycloalkenyl group when X is —O—, —S(O) m — or —N(R a )-; or is (2) when X is other than —O—, —S(O) m — or —N(R a )-, a hydrogen atom, or an optionally substituted straight or branched alkyl, alkenyl or alkynyl, alkoxy, alkylthio, —CO 2 R 9 (where R 9 is a hydrogen atom or an optionally substituted alkyl, aryl or aralkyl group), —CONR 10 R 11 (where R 10 and R 11 which may be the same or different is as described for R 9 ), —CSNR 10 R 11 , —CN or NO 2 group; or R 2 and R b , together with the carbon atom to which they are both attached, are linked to form an optionally substituted cycloalkyl or cycloalkenyl group optionally containing one or more X a atoms or groups; R 3 is an atom or group R 13 or -L 1 R 13 where L 1 is a linker group and R 13 is various substituents; R 4 is a hydrogen atom or is as defined for R 6 ; R 5 is a hydrogen or a fluorine atom, or an OR c group where R c is a hydrogen atom or an optionally substituted straight or branched alkyl, alkenyl, alkoxyalkyl, alkanoyl, formyl, carboxamido, thiocarboxamido, cycloalkyl, or cycloalkenyl group; R 6 is a group —(CH 2 ) n Ar where Ar is an optionally substituted monocyclic or bicyclic aryl ring optionally interrupted by one or more heteroatoms —O—, —S— or —N— and n is zero or the integer 1, 2 or 3; R 7 and R 8 , which may be the same or different, is a hydrogen or a fluorine atom, or an optionally substituted straight or branched alkyl group; and the salts, solvates, prodrugs, hydrates and N-oxides thereof. Compounds according to the invention are phosphodiesterase type IV inhibitors and are useful in the prophylaxis and treatment of disease such as asthma where an unwanted inflammatory response or muscular spasm is present.

  描述了一般式（1）：1的化合物，其中═W-是（1）═C（Y）-，其中Y是卤素原子，或烷基，或-XaR1基团，其中Xa是-O-，-S（O）m- [其中m为零或值为1或2的整数]，或N（Ra）- [其中Ra是氢原子或可选择取代的烷基基团]，R1是氢原子或可选择取代的烷基基团或（2）═N-; X如上所述为Xa，或者是链-CR═C（Rb）-或[ -CH（R）] q-CH（Rb）-，其中R是氢或氟原子或甲基基团，Rb如下所述为R2，q为零或整数1; R2是（1）可选择取代的烷基，烯基，环烷基或环烯基基团，当X为-O-，-S（O）m-或-N（Ra）-时；或（2）当X不是-O-，-S（O）m-或-N（Ra）-时，是氢原子，或可选择取代的直链或支链烷基，烯基或炔基，烷氧基，烷硫基，-CO2R9（其中R9是氢原子或可选择取代的烷基，芳基或芳基烷基），-CONR10R11（其中R10和R11可以相同或不同，如R9所述），-CSNR10R11，-CN或NO2基团; 或R2和Rb与它们都连接的碳原子一起形成可选择取代的环烷基或环烯基基团，可选地含有一个或多个Xa原子或基团; R3是一个原子或基团R13或-L1R13，其中L1是连接基团，R13是各种取代基; R4是氢原子或如R6所定义的基团; R5是氢或氟原子，或ORc基团，其中Rc是氢原子或可选择取代的直链或支链烷基，烯基，烷氧基，烷酰基，甲酰基，羧酰胺，硫代羧酰胺，环烷基或环烯基基团; R6是-（CH2）nAr基团，其中Ar是可选择取代的单环或双环芳基环，可选择地被一个或多个杂原子-O-，-S-或-N-中断，n为零或整数1,2或3; R7和R8，可以相同或不同，是氢或氟原子，或可选择取代的直链或支链烷基; 以及它们的盐，溶剂化合物，前药，水合物和N-氧化物。根据本发明的化合物是磷酸二酯酶IV抑制剂，可用于预防和治疗疾病，如哮喘，在该疾病中存在不需要的炎症反应或肌肉痉挛。
• Cyclo(alkyl and alkenyl)phenyl-alkenylyl(aryl and heteroaryl)compounds
  申请人：Celltech Therapeutics Limited

  公开号：US05633257A1

  公开（公告）日：1997-05-27

  Compounds of general formula (1) ##STR1## are described wherein Y is a halogen atom or a group --OR.sup.1, wherein R.sup.1 is an optionally substituted alkyl group; X is --O--, --S--, or --N(R.sup.6), wherein R.sup.6 is a hydrogen atom or an optionally substituted alkyl group; R.sup.2 is an optionally substituted cycloalkyl or cycloalkenyl group; R.sup.3 and R.sup.4, which may be the same or different, is each a hydrogen atom or an optionally substituted alkyl, --CO.sub.2 R.sup.7 (wherein R.sup.7 is a hydrogen atom, am optionally substituted alkyl, aralkyl, aryl, aryloxyalkyl, alkanoyloxyalkyl or aroyloxyalkyl group), --CONR.sup.8 R.sup.9 (where R.sup.8 and R.sup.9, which may be the same or different, is as defined for R.sup.7), --CSNR.sup.8 R.sup.9, --CN or --CH.sub.2 CN group; Z is --(CH.sub.2).sub.n -- where n is zero or an integer 1, 2 or 3; R.sup.5 is an optionally substituted monocyclic or bicyclic aryl group optionally containing one or more heteroatoms selected from oxygen, sulphur or nitrogen atoms; and the salts, solvates, hydrates, prodrugs and N-oxides thereof. Compounds according to the invention are potent and selective phosphodiesterase type IV inhibitors and are useful in the prophylaxis and treatment of diseases such as asthma where an unwanted inflammatory response or muscular spasm is present.

  描述了一般式（1）##STR1##的化合物，其中Y是卤素原子或基团—OR.sup.1，其中R.sup.1是可选择取代的烷基基团；X是—O—，—S—或—N（R.sup.6），其中R.sup.6是氢原子或可选择取代的烷基基团；R.sup.2是可选择取代的环烷基或环烯基基团；R.sup.3和R.sup.4，可能相同也可能不同，分别是氢原子或可选择取代的烷基，—CO.sub.2R.sup.7（其中R.sup.7是氢原子、可选择取代的烷基、芳基烷基、芳基、芳基氧基烷基、脂肪酰氧基烷基或芳酰氧基烷基基团），—CONR.sup.8R.sup.9（其中R.sup.8和R.sup.9，可能相同也可能不同，与R.sup.7定义相同），—CSNR.sup.8R.sup.9，—CN或—CH.sub.2CN基团；Z是—（CH.sub.2）.sub.n—，其中n为零或整数1、2或3；R.sup.5是可选择取代的单环或双环芳基基团，可选地含有一个或多个从氧、硫或氮原子中选择的杂原子；以及其盐、溶剂合物、水合物、前药和N-氧化物。根据本发明的化合物是有效的选择性磷酸二酯酶IV抑制剂，并可用于预防和治疗哮喘等疾病，其中存在不需要的炎症反应或肌肉痉挛。