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US 6,387,953 B1Granted
Inhibition of TNF-(α)-initiated neutrophil response
AssigneeBrigham and Women's Hopsital
InventorCharles N. Serhan
Life of this patent
Estimating the term…
Abstract
The impact of lipoxin A4 (LXA4) and aspirin-triggered-lipoxins (ATL) was investigated in tumor necrosis factor (TNFα)-initiated neutrophil (PMN) responses in vitro and in vivo using metabolically stable LX analogs. At concentrations as low as 1-10 nM, the LXA4 and ATL analogs each inhibited TNFα-stimulated superoxide anion generation and IL-1β release by human PMN.
Claims24
A method for modulating a disease or condition associated with TNFα initiated polymorphoneutrophil (PMN) inflammation in a subject, comprising
- administering to the subject an effective anti-inflammatory amount of a lipoxin analog having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O—or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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, such that a disease or condition associated with TNFα initiated polymorphoneutrophil (PMN) inflammation in a subject is modulated.
30 more elements
A method for treating TNFα initiated polymorphoneutrophil (PMN) inflammation in a subject, comprising
- administering to the subject an effective anti-TNFα amount of a lipoxin analog having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv, are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx is 1 to 8 carbon at 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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, such that TNFα initiated polymorphoneutrophil (PMN) inflammation is treated in a subject.
30 more elements
A method for modulating a disease or condition associated with TNFα initiated cytokine activity in a subject, comprising
- administering to the subject an effective anti-TNFα amount of a lipoxin analog having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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, such that a disease or condition associated with TNFα initiated cytokine activity in a subject is modulated.
30 more elements
A method for treating TNFα initiated cytokine inflammation in a subject, comprising
- administering to the subject an effective anti-TNFα amount of a lipoxin analog having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and
- wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched,
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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, such that TNFα initiated cytokine inflammation is treated in a subject.
31 more elements
A method for modulating a disease or condition associated with TNFα initiated IL-β in a subject, comprising
- administering to the subject an effective anti-TNFα amount of a lipoxin analog having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv , and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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, such that a disease or condition associated with TNFα initiated IL-1β inflammation in a subject is modulated.
30 more elements
A method for treating TNFα initiated IL-1β inflammation in a subject, comprising
- administering to the subject an effective anti-TNFα amount of a lipoxin analog having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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, such that TNFα initiated IL-1β inflammation is treated in a subject.
30 more elements
A packaged pharmaceutical composition for treating a disease or condition associated with TNFα initiated polymorphoneutrophil (PMN) inflammation in a subject, comprising:
- a container holding a therapeutically effective amount of at least one lipoxin compound having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, and Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Z ii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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
- instructions for using said lipoxin compound for treating a disease or condition associated with TNFα initiated polymorphoneutrophil (PMN) inflammation in the subject.
32 more elements
A packaged pharmaceutical composition for treating TNFα initiated polymorphoneutrophil (PMN) inflammation in a subject, comprising:
- a container holding a therapeutically effective amount of at least one lipoxin compound having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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
- instructions for using said lipoxin compound for treating TNFα initiated polymorphoneutrophil (PMN) inflammation in the subject.
32 more elements
A packaged pharmaceutical composition for treating a disease or condition associated with TNFα initiated cytokine activity in a subject, comprising:
- a container holding a therapeutically effective amount of at least one lipoxin compound having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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
- instructions for using said lipoxin compound for treating a disease or condition associated with TNFα initiated cytokine activity in the subject.
32 more elements
A packaged pharmaceutical composition for treating TNFα initiated cytokine activity in a subject, comprising:
- a container holding a therapeutically effective amount of at least one lipoxin compound having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or
- branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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
- instructions for using said lipoxin compound for treating TNFα initiated cytokine activity in the subject.
33 more elements
A packaged pharmaceutical composition for treating a disease or condition associated with TNFα initiated IL-1β inflammation in a subject, comprising:
- a container holding a therapeutically effective amount of at least one lipoxin compound having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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
- instructions for using said lipoxin compound for treating a disease or condition associated with TNFα initiated IL-1β inflammation in the subject.
32 more elements
A packaged pharmaceutical composition for treating TNFα initiated IL-1β inflammation in a subject, comprising:
- a container holding a therapeutically effective amount of at least one lipoxin compound having the formula
- wherein X is R1, OR1, or SR1;
- wherein R1 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 Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Q1 is (C═O), SO2 or (CN), provided when Q1 is CN, then X is absent;
- wherein Q3 and Q4 are each independently O, S or NH;
- wherein one of R2 and R3 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) RaQ2Rb wherein Q2 is —O— or —S—;
- wherein Ra is alkylene of 0 to 6 carbons atoms, inclusive, which may be straight chain or branched and wherein Rb is alkyl of 0 to 8 carbon atoms, inclusive, which may be straight chain or branched, provided when Rb is 0, then Rb is a hydrogen atom;
- wherein R4 is
- (a) H;
- (b) an alkyl of 1 to 6 carbon atoms, inclusive, which may be a straight chain or branched;
- wherein R5 is
- wherein Zi, Zii, Ziii, Ziv and Zv are each independently selected from —NO2, —CN, —C(═O)—R1, —SO3H, a hydrogen atom, halogen, methyl, —ORx, wherein Rx 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 Y1 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 CHaZb where a+b=3, a=0 to 3, b=0 to 3 and Z is cyano, nitro or a halogen;
- wherein R6 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
- instructions for using said lipoxin compound for treating TNFα initiated IL-1β inflammation in the subject.
32 more elements
Dependencies are inferred from the claim text.