(R,S)-(α)-ethyl-3-pyridinebutanol | 119981-17-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R,S)-(α)-ethyl-3-pyridinebutanol
• 英文别名: (R,S)-alpha-ethyl-3-pyridinebutanol；6-Pyridin-3-ylhexan-3-ol
• CAS: 119981-17-8
• 化学式: C₁₁H₁₇NO
• 分子量: 179.262
• InChiKey: BBIXSYYMPNVTPQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (R,S)-(α)-ethyl-3-pyridinebutanol 在 草酰氯 、 ammonium acetate 、 sodium cyanoborohydride 、 二甲基亚砜 、 1-羟基苯并三唑一水物 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 76.5h， 生成 (R,R*)-α-hydroxy-N-<1-ethyl-4-(3-pyridinyl)butyl>benzeneacetamide
  参考文献：
  名称：

  Pentadienyl carboxamide derivatives as antagonists of platelet activating factor

  摘要：

  A series of N-[4-(3-pyridinyl)butyl]-5,5-disubstituted-pentadienamides was prepared and evaluated for PAF-antagonist activity. Compounds were assayed in vitro in a PAF-binding assay employing washed, whole dog platelets as the receptor source and in vivo after intravenous or oral administration for their ability to prevent PAF-induced bronchoconstriction in guinea pigs. Criteria required for good oral activity in the latter model include an (E,-E)-5-phenyl-2,4-pentadienamide, a second phenyl or a four- or five-carbon alkyl moiety in the 5-position of the diene, and an (R)-[1-alkyl-4-(3-pyridinyl)butyl] substituent on the carboxamide nitrogen atom. The alkyl substituent on this side chain can be methyl, ethyl, or cyclopropyl. Two members of this series, [R-(E)]-5,5-bis(4-methoxy-phenyl)-N- [1-methyl-4-(3-pyridinyl)butyl]- 2,4-pentadienamide (31) and [R-(E,E)]-5-(4-methoxyphenyl)-N-[1-methyl-4- (3-pyridinyl)butyl]-2,4-decadienamide (58), were selected for further pharmacological evaluation. Both were found to be substantially longer acting after oral administration than the corresponding S enantiomers in the guinea pig bronchoconstriction assay. A second in vivo model used to evaluate PAF antagonists determines the ability of test compounds to decrease the area of skin wheals induced by an intradermal injection of PAF. In this model, using both rats and guinea pigs, compounds 31 and 58 were found to be as active as the reference PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-6H- 1-(4-morpholinyl)-1-propanone (45).

  DOI：

  10.1021/jm00128a026
• 作为产物：
  描述：

  5-己炔-3-醇 在 platinum(IV) oxide 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 5.0h， 生成 (R,S)-(α)-ethyl-3-pyridinebutanol
  参考文献：
  名称：

  Pentadienyl carboxamide derivatives as antagonists of platelet activating factor

  摘要：

  A series of N-[4-(3-pyridinyl)butyl]-5,5-disubstituted-pentadienamides was prepared and evaluated for PAF-antagonist activity. Compounds were assayed in vitro in a PAF-binding assay employing washed, whole dog platelets as the receptor source and in vivo after intravenous or oral administration for their ability to prevent PAF-induced bronchoconstriction in guinea pigs. Criteria required for good oral activity in the latter model include an (E,-E)-5-phenyl-2,4-pentadienamide, a second phenyl or a four- or five-carbon alkyl moiety in the 5-position of the diene, and an (R)-[1-alkyl-4-(3-pyridinyl)butyl] substituent on the carboxamide nitrogen atom. The alkyl substituent on this side chain can be methyl, ethyl, or cyclopropyl. Two members of this series, [R-(E)]-5,5-bis(4-methoxy-phenyl)-N- [1-methyl-4-(3-pyridinyl)butyl]- 2,4-pentadienamide (31) and [R-(E,E)]-5-(4-methoxyphenyl)-N-[1-methyl-4- (3-pyridinyl)butyl]-2,4-decadienamide (58), were selected for further pharmacological evaluation. Both were found to be substantially longer acting after oral administration than the corresponding S enantiomers in the guinea pig bronchoconstriction assay. A second in vivo model used to evaluate PAF antagonists determines the ability of test compounds to decrease the area of skin wheals induced by an intradermal injection of PAF. In this model, using both rats and guinea pigs, compounds 31 and 58 were found to be as active as the reference PAF antagonist 3-[4-(2-chlorophenyl)-9-methyl-6H- 1-(4-morpholinyl)-1-propanone (45).

  DOI：

  10.1021/jm00128a026

文献信息

• Substituted alkene carboxylic acid amides and derivatives
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0298466A2

  公开（公告）日：1989-01-11

  There are described compounds of the general formula wherein Y and Y′ are hydrogen or taken together are O or S, *A is paraphenylene or *-(CH₂)n-(X)s-(CH₂)r-, X is O, S or -CH=CH-, n and r, independently are integers from 0 to 3, m is the integer 0 or 1, s is the integer 0 or 1, provided that when s is 1, n+m is at least 2, t is an integer from 0 to 10, R₁ and R₂, independently, are lower alkyl, lower alkenyl or aryl, or one of R₁ and R₂ is hydrogen and the other is W is -CX₃=CX₄-, -CH₂-CH₂-, -CH₂-, O, S or -NX₅-, X₁ is lower alkyl, phenyl or phenyl with up to 3 substituents selected from lower alkoxy, lower alkyl and halogen, X₂, X₃ and X₄, independently, are hydrogen, lower alkyl, lower alkoxy or halogen, X₅ is lower alkyl, R₃ is hydrogen, lower alkyl or aryl, R₄ is hydrogen, lower alkyl, aryl, aryl-lower alkyl or acyl, R₅ is hydrogen or lower alkyl, R₆ is hydrogen,     lower alkyl, lower cycloalkyl, Het-lower alkyl or aryl, Het is a monocyclic 6-membered heteroaromatic radical containing one or two nitrogen atoms, which radical may be substituted by lower alkyl, halogen or aryl, and the asterisk denotes the point of attachment, when R₅ and R₆ are different, enantiomers and racemic mixtures thereof, when R₁ and R₂ are different, geometric isomers thereof, and pharmaceutically acceptable acid addition salts thereof. These compounds exhibit activity as platelet activating factor (PAF) antagonists and are, therefore, useful in disease states characterized by excess platelet activating factor or for the prevention and treatment of cardiovascular diseases, pulmonary diseases, immunological disorders, inflammatory diseases, dermatological disorders, shocks or transplant rejections.

  所述化合物通式如下 其中 Y 和 Y′为氢或合起来为 O 或 S，*A 为对苯二甲酸或 *-(CH₂)n-(X)s-(CH₂)r-，X 为 O、S 或-CH=CH-，n 和 r 独立地为 0 至 3 的整数，m 为 0 或 1 的整数、s 是 0 或 1 的整数，条件是当 s 为 1 时，n+m 至少为 2，t 是 0 至 10 的整数，R₁ 和 R₂ 独立地是低级烷基、低级烯基或芳基，或者 R₁ 和 R₂ 中的一个是氢，另一个是 W 是-CX₃=CX₄-、-CH₂-CH₂-、-CH₂-、O、S 或-NX₅-，X₁ 是低级烷基、苯基或带有最多 3 个选自低级烷氧基、低级烷基和卤素的取代基的苯基，X₂、X₃ 和 X₄ 独立地、是氢、低级烷基、低级烷氧基或卤素，X₅ 是低级烷基，R₃ 是氢、低级烷基或芳基，R₄ 是氢、低级烷基、芳基、芳基-低级烷基或酰基，R₅ 是氢或低级烷基，R₆ 是氢、 R₅是氢或低级烷基，R₆是氢、低级烷基、低级环烷基、Het-低级烷基或芳基，Het 是含有一个或两个氮原子的单环六元杂芳基，该基可被低级烷基、卤素或芳基取代，星号表示连接点、 当 R₅ 和 R₆ 不同时，其对映体和外消旋混合物；当 R₁ 和 R₂ 不同时，其几何异构体；以及其药学上可接受的酸加成盐。 这些化合物具有血小板活化因子（PAF）拮抗剂的活性，因此可用于以血小板活化因子过量为特征的疾病状态，或用于预防和治疗心血管疾病、肺部疾病、免疫性疾病、炎症性疾病、皮肤病、休克或移植排斥反应。
• Pentadienamide PAF-Antagonisten
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0299379A1

  公开（公告）日：1989-01-18

  Es werden Verbindungen der allgemeinen Formel worin Y ein Sauerstoff- oder Schwefelatom, *A Paraphenylen oder *-(CH2)n-(X)m-(CH2)r- , X eine Sauerstoff-oder Schwefelatom oder -CH=CH-, n und r unabhängig voneinander eine ganze Zahl von 0 - 3, s die Zahl 0 oder 1, m die Zahl 0 oder 1, wobei n + mindestens 2 ist, wenn m die Zahl 1 bedeutet, R1 und R2 unabhängig voneinander Wasserstoff, niederes Alkyl, niederes Cycloalkyl, niederes Alkenyl, Het oder Aryl, R3, R4 und R8 unabhängig voneinander Wasserstoff, niederes Alkyl oder Aryl, Rs und R7 unabhängig voneinander Wasserstoff oder niederes Alkyl, R6 Wasserstoff, niederes Alkyl, niederes Cycloalkyl, Het-niederes Alkyl oder Aryl, Het eine monocyclische, 5- oder 6-gliedrige heteroaromatische oder eine bicyclische heteroaromatische Gruppe, welche ein oder zwei Heteroatome ausgewählt aus Stickstoff, Sauerstoff und Schwefel enthält, und welche gegebenenfalls durch niederes Alkyl, Halogen oder Aryl substituiert ist, bedeuten und das Sternchen die Verknüpfungsstelle bezeichnet, und, sofern R6 und R7 verschieden sind, enantiomere und racemische Mischungen davon, sofern R1 und R2 verschieden sind, geometrische Isomeren davon und pharmazeutisch annehmbare Säureadditionssalze davon beschrieben. Die Verbindungen der Formel I entfalten Wirkungen als PAF-Antagonisten und können daher bei Krankheiten verwendet werden, welche durch erhöhtes PAF charakterisiert sind, oder zur Verhütung oder Behandlung von Kreislauferkrankungen, Lungenkrankheiten, immunologischen Störungen, Entzündungen, dermotologischen Krankheiten, Schocks oder Transplantatabstossungen.

  通式如下的化合物 其中 Y 是氧原子或硫原子，*A 是对苯二甲酸基或 *-(CH2)n-(X)m-(CH2)r-，X 是氧原子或硫原子或 -CH=CH-，n 和 r 独立地互为 0 - 3 的整数，s 是数字 0 或 1，m 是数字 0 或 1，其中 n + 至少为 2、当 m 为 1 时，R1 和 R2 独立地为氢、低级烷基、低级环烷基、低级烯基、Het 或芳基，R3、R4 和 R8 独立地为氢、低级烷基或芳基，Rs 和 R7 独立地为氢或低级烷基、R6 是氢、低级烷基、低级环烷基、Het-低级烷基或芳基，Het 是单环、5 或 6 元杂芳族或双环杂芳族基团，含有一个或两个选自氮、氧和硫的杂原子、当 R6 和 R7 不同时，其对映异构体和外消旋混合物；当 R1 和 R2 不同时，其几何异构体和药学上可接受的异构体。 式 I 化合物的异构体及其药学上可接受的酸加成盐。 式 I 的化合物可作为 PAF 拮抗剂，因此可用于以 PAF 升高为特征的疾病，或用于预防或治疗循环系统疾病、肺部疾病、免疫紊乱、炎症、皮肤病、休克或移植排斥反应。
• N-HYDROXYUREA DERIVATIVES AND MEDICINAL COMPOSITIONS CONTAINING THE SAME
  申请人：Nikken Chemicals Company, Limited

  公开号：EP0949259A1

  公开（公告）日：1999-10-13

  An N-hydroxyurea derivative having an antiallergic action or anti-inflammatory action having the formula (I): wherein, either one of R1, R3, and R4 represents A, either one of the other groups of R1, R3, and R4 and R2 represents a 3-pyridyl group or 3-pyridylalkyl group, the remaining groups of R1, R2, R3, and R4 independently represent a hydrogen atom, halogen atom, or a substituted or unsubstituted C1 to C8 alkyl group, R5 represents a hydrogen atom or lower alkyl group, R6 represents a hydrogen atom, lower alkyl group, C3 to C7 cycloalkyl group, or a substituted or unsubstituted phenyl group, where the substituent represents a halogen atom, lower alkyl group, or lower alkoxy group, B represents a bond, C1 to C20 alkylene group, C2 to C8 alkenylene group, or C2 to C8 alkynylene group or B-C(R5) represents a C2 to C6 alkylene group having a benzene ring in the middle thereof or its pharmacologically acceptable salt or the hydrate or solvate thereof.

  一种具有抗过敏作用或抗炎作用的 N-羟基脲衍生物，具有式（I）： 其中，R1、R3 和 R4 中的任一基团代表 A，R1、R3 和 R4 的其它基团和 R2 中的任一基团代表 3-吡啶基或 3-吡啶烷基，R1、R2、R3 和 R4 的其余基团独立地代表氢原子、卤素原子或取代或未取代的 C1 至 C8 烷基，R5 代表氢原子或低级烷基，R6 代表氢原子、低级烷基、C3 至 C7 环烷基或取代或未取代的苯基、B 代表键、C1 至 C20 亚烷基、C2 至 C8 烯基或 C2 至 C8 亚炔基，或 B-C(R5)代表中间有苯环的 C2 至 C6 亚烷基或其药理学上可接受的盐或其水合物或溶液。
• GUTHRIE, ROBERT W.;KAPLAN, GERALD L.;MENNONA, FRANCIS A.;TILLEY, JEFFERSO+, J. MED. CHEM., 32,(1989) N, C. 1820-1835
  作者：GUTHRIE, ROBERT W.、KAPLAN, GERALD L.、MENNONA, FRANCIS A.、TILLEY, JEFFERSO+

  DOI：——

  日期：——
• US4786646A
  申请人：——

  公开号：US4786646A

  公开（公告）日：1988-11-22