Method for treating airway hyper-responsiveness with lipoxin analogs
The use of lipoxin analogs for the treatment or prevention of asthma and asthma related diseases is described. In particular, acetylenic lipoxin analogs are effective for the treatment and prevention of eosinophil recruitment involved with the inflammation processes associated with asthma, asthma like conditions, and lung injuries associated from airway inflammation or infection as brought about by leukocyte-mediated injury from within.
1. A method for treating airway hyper-responsiveness comprising the step of administering to a subject in need thereof, a therapeutically effective amount of a lipoxin analog having the formula
wherein X is R 1 , OR 1 , or SR 1 ;
wherein R 1 is
(i) a hydrogen atom;
(ii) an alkyl of 1 to 8 carbon atoms, inclusive, which may be straight chain or branched;
(iii) a cycloalkyl of 3 to 10 carbon atoms;
(iv) an aralkyl of 7 to 12 carbon atoms;
(v) phenyl;
(vi) substituted phenyl
wherein Z i , Z ii , Z iii , Z iv and Z v are each independently selected from —NO 2 , —CN, —C(═O)—R 1 , —SO 3 H, a hydrogen atom, halogen, methyl, —OR x , wherein R x is 1 to 8 carbon atoms, inclusive, which may be a straight chain or branched, and hydroxyl;
(vii) a detectable label molecule; or
(viii) a straight or branched chain alkenyl of 2 to 8 carbon atoms, inclusive;
wherein Q 1 is (C═O), SO 2 or (CN), provided when Q 1 is CN, then X is absent;
wherein one of R 2 and R 3 is a hydrogen atom and the other is
(a) H;
(b) an alkyl of 1 to 8 carbon atoms, inclusive, which may be a straight chain or branched;
(c) a cycloalkyl of 3 to 6 carbon atoms, inclusive;
(d) an alkenyl of 2 to 8 carbon atoms, inclusive, which may be straight chain or branched; or
(e) R a Q 2 R b wherein Q 2 is —O— or —S—; wherein R a is alkylene of 0 to 6 carbon atoms, inclusive, which may be straight chain or branched and wherein R b is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when R b is 0, then R b is a hydrogen atom;
wherein R 4 is
(a) H;
(b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
wherein R 5 is
wherein Z i , Z ii , Z iii , Z iv and Z v are each independently selected from —NO 2 , —CN, —C(═O)—R 1 , —SO 3 H, a hydrogen atom, halogen, methyl, —OR x , wherein R x is 1 to 8 carbon atoms, inclusive, which may be a straight chain or branched, and hydroxyl or a substituted or unsubstituted, branched or unbranched alkyl group;
wherein R 6 is
(a) H;
(b) an alkyl from 1 to 4 carbon atoms, inclusive, straight chain or branched;
wherein T is O or S, and pharmaceutically acceptable salts thereof.