IP Library › Granted Patent US 6,960,674
Granted Patent B2
US 6,960,674 · App. 10/366,194 · Granted Nov 1, 2005

Prevention of neutrophil recruitment

Assignee: The Brigham & Women's Hospital, Inc.
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Quick Facts
Patent No.
US 6,960,674
App. No.
10/366,194
Granted
Nov 1, 2005
Kind
B2
Abstract

Aspirin (ASA) triggers a switch in the biosynthesis of lipid mediators, inhibiting prostanoid production and initiating 15-epi-lipoxin generation, through the acetylation of cyclooxygenase II.

Claims (85)

1. A pharmaceutical composition comprising 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, —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 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, —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 Y 1 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 is O or S, and pharmaceutically acceptable salts thereof; and

a pharmaceutically acceptable carrier, provided 16-phenoxy-LXA 4 is excluded and provided when said compound is 15-epi-16-(para-fluoro)-phenoxy-LXA 4 , said pharmaceutically acceptable carrier is not a ketone.

2. The pharmaceutical composition of claim 1 , wherein said ketone is not acetone.

3. A pharmaceutical composition comprising 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, —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 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, —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; and

a pharmaceutically acceptable carrier, provided 16-phenoxy-LXA 4 is excluded and provided when said compound is 15-epi-16-(para-fluoro)-phenoxy-LXA 4 , said pharmaceutically acceptable carrier is not a ketone.

4. The pharmaceutical composition of claim 3 , wherein said ketone is not acetone.

5. A pharmaceutical composition comprising 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, —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 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; and

a pharmaceutically acceptable carrier, provided 16-phenoxy-LXA 4 is excluded and provided when said compound is 15-epi-16-(para-fluoro)-phenoxy-LXA 4 , said pharmaceutically acceptable carrier is not a ketone.

6. The pharmaceutical composition of claim 5 , wherein said ketone is not acetone.

Assignments (1)
CONFIRMATORY LICENSE Recorded Apr 1, 2023
From: THE BRIGHAM AND WOMEN'S HOSPITAL, INC.
To: NATIONAL INSTITUTES OF HEALTH - DIRECTOR DEITR
Reel/Frame 063198/0350 →
Continuity (4)
Continuation 1017674400 · Jun 20, 2002
Division 0952574200 · Mar 14, 2000
Provisional Application 6012520900 · Mar 18, 1999
Related Publication 20030191332A1 · Oct 9, 2003