5-[4-(Quinolin-2-ylmethoxy)phenyl]pentanoic acid | 129649-22-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 5-[4-(Quinolin-2-ylmethoxy)phenyl]pentanoic acid
• CAS: 129649-22-5
• 化学式: C₂₁H₂₁NO₃
• 分子量: 335.403
• InChiKey: GEPCPHZJFQZONY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(4-羟基苯基)戊酸甲酯 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 72.75h， 生成 5-[4-(Quinolin-2-ylmethoxy)phenyl]pentanoic acid
  参考文献：
  名称：

  The development of a novel series of (quinolin-2-ylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 3. Structural variation of the acidic side chain to give antagonists of enhanced potency

  摘要：

  This paper is the third in a series outlining the development of orally active sulfido peptide leukotriene antagonists containing a (quinolin-2-ylmethoxy)phenyl moiety. In this work the systematic variation of the acid side chain substituents led to dramatic and reproducible changes in the oral activity of these compounds, presumably due to alterations in their pharmacokinetic properties. The most potent compound identified, 5-[4-[4-(quinolin-2-yl-methoxy)phenyl]-3-methylbutyl]tetrazole (32), represents a convergence of good in vitro antagonist activity and a 3-10-fold improvement in oral potency over the current clinical candidate 2. The new findings from these optimization studies are as follows: oxygen substitution in the acid side chain was not necessary for antagonist activity, in vitro and in vivo activity was enhanced by alkyl or phenyl substitution on the gamma-carbon of the acid side chain of para-substituted (quinolin-2-ylmethoxy)phenyl derivatives, and free rotation about the side chain carbon atom adjacent to the (quinolin-2-ylmethoxy)phenyl ring was required for activity. The lead compound of this report (32) is a competitive inhibitor of [3H]LTD4 binding to receptor membrane purified from guinea pig lung (Ki = 12 +/- 3 nM) and of the spasmogenic activity of LTC4, LTD4, and LTE4 in guinea pig lung strip. Dosed orally in guinea pigs, this compound blocks LTD4-induced bronchoconstriction (ED50 0.8 mg/kg) and antigen-induced systemic anaphylaxis (ED50 = 1.2 mg/kg).

  DOI：

  10.1021/jm00172a024

文献信息

• [EN] SYMMETRICAL bis-HETEROARYLMETHOXYPHENYLALKYL CARBOXYLATES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS<br/>[FR] bis-HETEROARYLMETHOXYPHENYLALKYL CARBOXYLATES SYMETRIQUES INHIBANT LA BIOSYNTHESE DE LEUKOTRIENE
  申请人：ABBOTT LABORATORIES

  公开号：WO1997012867A1

  公开（公告）日：1997-04-10

  (EN) Compounds having formula (I), wherein W is the same at each occurrence and is selected from optionally substituted quinolyl, optionally substituted benzothiazolyl, optionally substituted benzoxazolyl, optionally substituted benzimidazolyl, optionally substituted quinoxalyl, optionally substituted pyridyl, optionally substituted pyrimidyl, and optionally substituted thiazolyl; R1 and R2 are independently selected from hydrogen, alkyl, haloalkyl, alkoxy, halogen; R3 is a valence bond or is selected from hydrogen and alkyl; X is a valence bond or is selected from alkylene, alkenylen, and alkynylene; and Z is selected from (a) COM, (b) CH=N-O-A-COM, (c) CH2-O-N=A-COM wherein A is selected from alkylene and cycloalkylene, and M is selected from (a) a pharmaceutically acceptable metabolically cleavable group, (b) -OR6, (c) -NR7R8, (d) -NR6SO2R9, (e) -NH-Tetrazolyl, and (f) glycinyl inhibit leukotriene biosynthesis and are useful in the treatment of allergic and inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method of inhibiting leukotriene biosynthesis.(FR) L'invention porte sur des composés représentés par la formule (I), où W est identique à chaque occurrence, et est choisi parmi quinolyle facultativement substitué, benzothiazolyle facultativement substitué, benzoxazolyle facultativement substitué, benzimidazolyle facultativement subtitué, quinoxalyle facultativement substitué, pyridyle facultativement substitué, pyrimidyle facultativement substitué, et thiazolyle facultativement substitué; R1 et R2 sont choisis chacun séparément parmi hydrogène, alkyle, haloalkyle, alcoxy, halogène; R3 est une liaison de valence ou est choisi parmi hydrogène et alkyl; et Z est choisi parmi (a) COM, (b) CH=N-O-A-COM, (c) CH2-O-N=A-COM où A est choisi parmi alkylène et cycloalkylène, et M est choisi parmi (A) un groupe métaboliquement clivable et pharmaceutiquement acceptable, (b) -OR6, (c) -NR7R8, (d) -NR6SO2R9, (e) -NH-Tetrazolyl, et (f) glycinyle. Ces composés inhibent la biosynthèse de leukotriène, et sont utilisés dans le traitement d'allergies et d'inflammations. L'invention porte également sur des compositions inhibant la biosynthèse de leukotriène et sur un procédé d'inhibition de la biosynthèse de leukotriène.

  化合物的化学式为（I），其中W在每次出现时相同，并从可选择的取代的喹啉基，可选择的取代的苯并噻唑基，可选择的取代的苯并噁唑基，可选择的取代的苯并咪唑基，可选择的取代的喹喔啉基，可选择的取代的吡啶基，可选择的取代的嘧啶基和可选择的取代的噻唑基中选择; R1和R2分别选择自氢，烷基，卤代烷基，烷氧基，卤素; R3是一个价键或选择自氢和烷基; X是一个价键或选择自烷基，烯基和炔基; Z选择自（a）COM，（b）CH = N-O-A-COM，（c）CH2-O-N = A-COM，其中A选择自烷基和环烷基，M选择自（a）药理学上可接受的代谢可裂解基团，（b）-OR6，（c）-NR7R8，（d）-NR6SO2R9，（e）-NH-Tetrazolyl和（f）甘氨酰基。这些化合物抑制白三烯生物合成，可用于治疗过敏和炎症性疾病状态。还公开了抑制白三烯生物合成的组合物和一种抑制白三烯生物合成的方法。
• GALEMMO, ROBERT A.;JOHNSON, WILLIAM H. (JR);LEARN, KEITH S.;LEE, THOMAS D+, J. MED. CHEM., 33,(1990) N0, C. 2828-2841
  作者：GALEMMO, ROBERT A.、JOHNSON, WILLIAM H. (JR)、LEARN, KEITH S.、LEE, THOMAS D+

  DOI：——

  日期：——
• SYMMETRICAL bis-HETEROARYLMETHOXYPHENYLALKYL CARBOXYLATES AS INHIBITORS OF LEUKOTRIENE BIOSYNTHESIS
  申请人：Abbott Laboratories

  公开号：EP0862557A1

  公开（公告）日：1998-09-09
• US5795900A
  申请人：——

  公开号：US5795900A

  公开（公告）日：1998-08-18
• USRE40558E1
  申请人：——

  公开号：USRE40558E1

  公开（公告）日：2008-10-28