Granted Patent B2

US 8,022,105 · App. 12/546,242 · Granted Sep 20, 2011

Assignee: The Brigham and Women's Hospital, Inc.

Abstract

Claims (71)

1. A method of modulating inflammation in a subject, comprising

administering to the subject an effective anti-inflammatory amount of a compound 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 carbons 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, —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 Q 3 and Q 4 , if present, are each independently O, S or NH;

wherein one of R 2 and R 3 , if present, 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 carbons 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, ——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 Y 1 , if present, is —OH, methyl, —SH, an alkyl of 2 to 4 carbon atoms, inclusive, straight chain or branched, an alkoxy of 1 to 4 carbon atoms, inclusive, or CH a Z b where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;

wherein R 6 is

(a) H;

(b) an alkyl from 1 to 4 carbon atoms, inclusive, straight chain or branched;

wherein T, if present, is O or S, and pharmaceutically acceptable salts thereof excluding 16-phenoxy-LXA 4 and 15-epi-16-(para-fluoro)-phenoxy-LXA 4 , such that inflammation in a subject is modulated.

2. A method of modulating inflammation in a subject, comprising

administering to the subject an effective anti-inflammatory amount of a compound having the formula

such that inflammation in a subject is modulated.

3. The method of claim 2 , further comprising a pharmaceutically acceptable carrier.

4. The method of claim 2 , further comprising a pharmaceutically acceptable carrier, wherein said pharmaceutical carrier is not a ketone.

5. A method of modulating a disease or condition associated with polymorphoneutrophil (PMN) inflammation in a subject, comprising

administering to the subject an effective anti-inflammatory amount of a compound having the formula

such that a disease or condition associated with polymorphoneutrophil (PMN) inflammation in a subject is modulated.

6. The method of claim 5 , further comprising a pharmaceutically acceptable carrier, wherein said pharmaceutical carrier is not a ketone.

7. A method of modulating a disease or condition associated with polymorphoneutrophil (PMN) inflammation in a subject, comprising

administering to the subject an effective anti-inflammatory amount of a compound 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 carbons 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, ——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 , if present, 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 carbons 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, ——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 Y 1 , if present, is —OH, methyl, —SH, an alkyl of 2 to 4 carbon atoms, inclusive, straight chain or branched, an alkoxy of 1 to 4 carbon atoms, inclusive, or CH a Z b where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;

wherein R 6 is

(a) H;

(b) an alkyl from 1 to 4 carbon atoms, inclusive, straight chain or branched;

wherein T, if present, is O or S, and pharmaceutically acceptable salts thereof excluding 16-phenoxy-LXA 4 and 15-epi-16-(para-fluoro)-phenoxy-LXA 4 ; and

a pharmaceutically acceptable carrier, such that a disease or condition associated with polymorphoneutrophil (PMN) inflammation in a subject is modulated.

Assignments (2)

Continuity (8)