Treatment for atherosclerosis and other cardiovascular and inflammatory diseases
First Claim
1. A method for the treatment of an inflammatory skin disease that is mediated by VCAM-1 comprising administering an effective amount to inhibit the expression of VCAM-1 of the dithiocarbamate of the formula A-SC(S)-Bwherein A is selected from the group consisting of hydrogen, a pharmaceutically acceptable cation, and a physiologically cleavable leaving group;
- and B is selected from the group consisting of alkyl, alkenyl, alkynyl, alkaryl, aralkyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, alkaryl, heterocyclic, alkylheterocyclic, C1-6 alkoxy-C1-10 alkyl, C1-6 alkylthio-C1-10 alkyl, NR2 R3, --(CHOH)n CH2 OH, wherein n is 0, 1, 2, 3, 4, 5, or 6, --(CH2)n CO2 R1, including alkylacetyl, alkylpropionyl, and alkylbutyryl, and hydroxy (C1-6)alkyl--, wherein R1 is hydrogen or a pharmaceutically acceptable cation, and R2 and R3 are independently isopropyl, butyl, isobutyl, t-butyl, pentyl, cyclopentyl, isopentyl, neopentyl, hexyl, isohexyl, or cyclohexyl, --(CHOH)n(CH2)OH, wherein n is 0, 1, 2, 3, 4, 5, or 6, or R2 and R3 together constitute a bridge.
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Abstract
Dithiocarboxylates, and in particular, dithiocarbamates, block the induced expression of the endothelial cell surface adhesion molecule VCAM-1, and are therefor useful in the treatment of cardiovascular disease, including atherosclerosis, post-angioplasty restenosis, coronary artery diseases, and angina, as well as noncardiovascular inflammatory diseases that are mediated by VCAM-1.
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Citations
10 Claims
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1. A method for the treatment of an inflammatory skin disease that is mediated by VCAM-1 comprising administering an effective amount to inhibit the expression of VCAM-1 of the dithiocarbamate of the formula A-SC(S)-B
wherein A is selected from the group consisting of hydrogen, a pharmaceutically acceptable cation, and a physiologically cleavable leaving group; and B is selected from the group consisting of alkyl, alkenyl, alkynyl, alkaryl, aralkyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, alkaryl, heterocyclic, alkylheterocyclic, C1-6 alkoxy-C1-10 alkyl, C1-6 alkylthio-C1-10 alkyl, NR2 R3, --(CHOH)n CH2 OH, wherein n is 0, 1, 2, 3, 4, 5, or 6, --(CH2)n CO2 R1, including alkylacetyl, alkylpropionyl, and alkylbutyryl, and hydroxy (C1-6)alkyl--, wherein R1 is hydrogen or a pharmaceutically acceptable cation, and R2 and R3 are independently isopropyl, butyl, isobutyl, t-butyl, pentyl, cyclopentyl, isopentyl, neopentyl, hexyl, isohexyl, or cyclohexyl, --(CHOH)n(CH2)OH, wherein n is 0, 1, 2, 3, 4, 5, or 6, or R2 and R3 together constitute a bridge. - View Dependent Claims (4, 5, 6, 7, 8, 9)
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2. A method for the treatment of a human endothelial cell disorder that is mediated by VCAM-1 comprising administering an effective amount to inhibit the expression of VCAM-1 of the dithiocarbamate of the formula A-SC(S)-B
wherein A is selected from the group consisting of hydrogen, a pharmaceutically acceptable cation, and a physiologically cleavable leaving group; and B is selected from the group consisting of alkyl, alkenyl, alkynyl, alkaryl, aralkyl, haloalkyl, haloalkenyl, haloalkynyl, aryl, alkaryl, heterocyclic, alkylheterocyclic, C1-6 alkoxy-C1-10 alkyl, C1-6 alkylthio-C1-10 alkyl, NR2 R3, --(CHOH)n CH2 OH, wherein n is 0, 1, 2, 3, 4, 5, or 6, --(CH2)n CO2 R1, including alkylacetyl, alkylpropionyl, and alkylbutyryl, and hydroxy (C1-6) alkyl--, wherein R1 is hydrogen or a pharmaceutically acceptable cation, and R2 and R3 are independently isopropyl, butyl, isobutyl, t-butyl, pentyl, cyclopentyl, isopentyl, neopentyl, hexyl, isohexyl, or cyclohexyl, --(CHOH)n(CH2)OH, wherein n is 0, 1, 2, 3, 4, 5, or 6, or R2 and R3 together constitute a bridge. - View Dependent Claims (3, 10)
Specification