omega-[(4-Phenyl-2-quinolyl)oxy]alkanoic acid derivatives: a new family of potent LTB4 antagonists.
A series of omega-[(4-phenyl-2-quinolyl)oxy]alkanoic acid derivatives was prepared which inhibited the binding of the leukotriene B4 to its receptors on guinea pig spleen membranes and on human polymorphonuclear leukocytes. A structure-activity relationship was investigated. The length of the carboxylic acid side chain was important for potent binding activity. The replacement of the oxygen atom at the beginning of the chain with other polar or nonpolar linking groups led to considerable loss of potency, indicating that the oxygen linking atom might be involved in the receptor recognition. alpha-Substitution on the carboxylic acid side chain led to substantially more potent compounds. Substitution on the phenyl ring and on the quinoline ring was also evaluated.
Labaudinière
R
R
Rhône-Poulenc Rorer, Centre de Recherche de Vitry-Alfortville, Departement de Chimie Pharmaceutique et de Biologie, Vitry-sur Seine, France.
Hendel
W
W
Terlain
B
B
Cavy
F
F
Marquis
O
O
Dereu
N
N
D000818:Animals; D006168:Guinea Pigs; D006801:Humans; D007975:Leukotriene B4 / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology; D011971:Receptors, Immunologic / Q000187:drug effects / Q000378:metabolism; D018102:Receptors, Leukotriene B4; D013329:Structure-Activity Relationship
D015363:Quinolones; D011971:Receptors, Immunologic; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4