Methods and products relating to 16-HETE analogs
AssigneeUniversity of Vermont and State Agricultural College
InventorsJohn R. Falck, Martin M. Bednar, Cordell E. Gross, Michael Balazy
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Abstract
The present invention includes 16-HETE analogs which are agonists and antagonists of 16-HETE. The compositions may be formulated in pharmaceutically acceptable formulations. The invention also includes methods and products for inhibiting neutrophil adhesion and neutrophil aggregation using the 16-HETE agonists. One method of the invention involves the administration of a 16-HETE agonist in combination with a thrombolytic agent to a patient suffering from thromboembolic stroke.
Claims55
A composition of a 16-hydroxyeicosatetraenoic acid analog comprising:
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- wherein R is selected from the group consisting of —C(O)—X—SO2—R1, —C(O)—X—CO—R1, —C(O)—X—C(OH)2—R1, —C(O)—X—C(NH)2—R1, —C(O)—X—C(NH2)2—R1, piperonyl, —CN, —OR′, —SR′, —NO2, —NR′R′, amino acid, —C(O)R′, —C(S)R′, —C(O)OR′, —C(S)OR′, —C(O)SR, —C(S)SR′, —C(O)N(R′)2, —C(O)C(O)R′, —C(S)C(O)R′, —C(O)C(S)R′, —C(S)C(S)R′, —C(O)C(O)OR′, —C(S)C(O)OR′, —C(O)C(S)OR′, —C(O)C(O)SR′, —C(S)C(S)OR′, —C(S)C(O)SR′, —C(O)C(S)SR′, —C(S)C(S)SR′, —C(O)C(O)N(R′)2, —C(S)C(O)N(R′)2, —C(O)C(S)N(R′)2, or —C(S)C(S)N(R′)2;
- wherein X is selected from the group consisting of O, NH, and a bond;
- wherein R1, R2, and R3 each independently is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, and heteroaryl;
- wherein each R′ is (CH2)x—NR″R″ and wherein R″ is independently selected from the group consisting of (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkoxy, (C1-C6) alkynyl, (C6-C20) aryl, (C6-C20) substituted aryl, (C6-C26) alkaryl, substituted (C6-C26) alkaryl, and (C5-C7) heteroaryl.
A 16-hydroxyeicosatetraenoic acid analog, comprising:
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- wherein R is selected from the group consisting of —C(O)—X—SO2—R1, —C(O)—X—CO—R1, —C(O)—X—C(OH)2—R1, —C(O)—X—C(NH)2—R1, —C(O)—X—C(NH2)2—R1, piperonyl, —CN, —OR′, —SR′, —NO2, —NR′R′, amino acid, —C(O)R′, —C(S)R′, —C(O)OR′, —C(S)OR′, —C(O)SR, —C(S)SR′, —C(O)N(R′)2, —C(O)C(O)R′, —C(S)C(O)R′, —C(O)C(S)R′, —C(S)C(S)R′, —C(O)C(O)OR′, —C(S)C(O)OR′, —C(O)C(S)OR′, —C(O)C(O)SR′, —C(S)C(S)OR′, —C(S)C(O)SR′, —C(O)C(S)SR′, —C(S)C(S)SR′, —C(O)C(O)N(R′)2, —C(S)C(O)N(R′)2, —C(O)C(S)N(R′)2, or —C(S)C(S)N(R′)2;
- wherein X is selected from the group consisting of O, NH, and a bond;
- wherein R1, R2, and R3 each independently is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, alkoxy, aryl, and heteroaryl;
- wherein each R′ is (CH2)z—NR″R″ and wherein R″ is independently selected from the group consisting of (C1-C6) alkyl, (C1-C6) alkenyl, (C1-C6) alkoxy, (C1-C6) alkynyl, (C6-C20) aryl, (C6-C20) substituted aryl, (C6-C26) alkaryl, substituted (C6-C26) alkaryl, and (C5-C7) heteroaryl.
A method of inhibiting leukotriene production in a neutrophil comprising:
- administering to a neutrophil, a 16-hydroxyeicosatetraenoic acid or an agonist thereof in an amount effective to inhibit leukotriene production.
A method of inhibiting leukotriene production in a subject having a condition mediated by leukotriene activity, comprising:
- administering to said subject having a condition mediated by leukotriene activity a 16-hydroxyeicosatetraenoic acid or an agonist thereof in an amount effective to inhibit leukotriene production.
A method for treating a subject to inhibit neutrophil adhesion and neutrophil aggregation, said method comprising the step of:
- administering to a subject having an adverse medical condition mediated by neutrophil adhesion and/or neutrophil aggregation 16-hydroxyeicosatetraenoic acid agonist in an amount effective to inhibit neutrophil adhesion and neutrophil aggregation.
42 The method as recited in claim 35, further comprising the step of administering to the subject a therapeutic agent other than and in addition to 16-hydroxyeicosatetraenoic acid agonist for treating the inflammatory condition.
A method for treating thromboembolic stroke, the method comprising the step of:
- administering to a subject experiencing a thromboembolic stroke, 16-hydroxyeicosatetraenoic acid agonist and a thrombolytic agent in an amount effective to reduce brain injury which would otherwise occur as a result of the stroke.
Dependencies are inferred from the claim text.