COMPOSITIONS AND METHODS OF USE FOR TREATING OR PREVENTING LIPID RELATED DISORDERS
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Abstract
Disclosed herein are novel compositions and methods for treating or preventing a variety of disorders and conditions associated with lipid metabolism. The methods generally include administering to a patient in need thereof a therapeutically effective amount of a pharmaceutical composition comprising one or more fibric acid or statin derivative compositions alone or in combination with one or more lipid altering agents and/or PDE inhibitors.
22 Citations
171 Claims
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1-149. -149. (canceled)
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150. A compound represented by the structure (I)
wherein R1 is chosen from H and halogen; -
R2 is chosen from H, halogen, cycloalkyl substituted with from 1 to 3 halogens, COR3, and (CH2)mNHOR3; R3 is phenyl substituted with from one to three halogen groups; Z is chosen from O and (CH2)nO; X is chosen from direct bond, O, NH, and an amino acid residue; R4 is chosen from OH, NO, NO2, an amino acid residue, a fabric acid residue, a guanidine residue, a tetrazolyl residue, an agmatine residue, an amino-containing compound residue;
a lower alkyl group terminating in ONO, (ONO2)p, or guanidine;
a resveratrol residue; and
an imidazoline receptor agonist residue; andm, n, and p are independently chosen from 1 to 3. - View Dependent Claims (151, 152, 153, 154)
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155. A composition for the prevention and/or treatment of lipid related disorders, said composition comprising:
- (1) a pharmaceutically acceptable carrier and (2) a therapeutically effective amount of a compound represented by the structure (I)
wherein R1 is chosen from H and halogen; R2 is chosen from H, halogen, cycloalkyl substituted with from 1 to 3 halogens, COR3, or (CH2)mNHOR3; R3 is phenyl substituted with from one to three halogen groups; Z is chosen from O or (CH2)nO; X is chosen from a direct bond, O, NH, or an amino acid residue; R4 is chosen from OH, NO, NO2, an amino acid residue, a fabric acid residue, a guanidine residue, a tetrazolyl residue, an agmatine residue, an amino-containing compound residue;
a lower alkyl group terminating in ONO, (ONO2)p, or guanidine;
a resveratrol residue;
or an imidazoline receptor agonist residue; andm, n, and p are independently chosen from 1 to 3. - View Dependent Claims (156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166)
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157. The composition according to claim 156, wherein said compound (II) is chosen from the following structures:
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158. The composition according to claim 156, wherein said compound (II) is chosen from the following structures:
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159. The composition according to claim 156, wherein said compound (II) is chosen from the following structures:
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wherein R10 is C1-C6 acyl.
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160. The composition according to claim 159, wherein said compound (II) is represented by the following structure:
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161. The composition according to claim 156, wherein said compound (II) is chosen from the following structures:
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wherein R11 is C1-C6 alkyl.
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162. The composition according to claim 161, wherein said compound (II) is represented by the following structure:
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163. The composition according to claim 155 further comprising at least one lipid altering agent.
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164. The composition according to claim 163, wherein said lipid altering agent is chosen from among:
- statins, fibrates, cholesterol-ester-transfer-protein (CETP) inhibitors, squalene synthase inhibitors, microsomal-triglyceride-transfer-protein (MTTP) inhibitors, cholesterol absorption inhibitors, soluble guanylate cyclase modulators, bile acid sequestrants, thyroid receptor agonists, LXR modulators, or antisense inhibitors of apoB-100 or C-reactive protein.
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165. The composition according to claim 155 further comprising a therapeutically effective amount of at least one phosphodiesterase inhibitor.
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166. A kit for treating a lipid metabolism disorder comprising, in one or more containers, a therapeutically effective amount of the composition according to claim 155, together with a label or packaging insert containing instructions for use.
- (1) a pharmaceutically acceptable carrier and (2) a therapeutically effective amount of a compound represented by the structure (I)
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167. A method for treating or preventing a lipid metabolism disorder, said method comprising:
- administering to a patient in need thereof a therapeutically effective amount of a composition comprising a compound represented by the structure (I)
wherein R1 is chosen from H and halogen; R2 is chosen from H, halogen, cycloalkyl substituted with from 1 to 3 halogens, COR3, or (CH2)mNHOR3; R3 is phenyl substituted with from one to three halogen groups; Z is chosen from O or (CH2)nO; X is chosen from a direct bond, O, NH, or an amino acid residue; R4 is chosen from OH, NO, NO2, an amino acid residue, a fabric acid residue, a guanidine residue, a tetrazolyl residue, an agmatine residue, an amino-containing compound residue;
a lower alkyl group terminating in ONO, (ONO2)p, or guanidine;
a resveratrol residue;
or an imidazoline receptor agonist residue; andm, n, and p are independently chosen from 1 to 3. - View Dependent Claims (168, 169, 170, 171)
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169. The method according to claim 167, wherein said lipid metabolism disorder is chosen from:
- dyslipidemia, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, sitosterolemia, or fatty liver disease.
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170. The method according to claim 167, wherein said patient is diabetic.
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171. The method according to claim 167, wherein said method is effective in said patient for:
- (i) lowering glycosylated hemoglobin levels (HbA1C);
(ii) lowering fasting plasma glucose (FPG) levels;
(iii) lowering peak and 2-hour post-prandial glucose (PPG) levels;
(iv) improving insulin sensitivity or reducing insulin resistance;
(v) increasing insulin secretion;
or (vi) reducing the risk of developing diabetes-associated complications.
- (i) lowering glycosylated hemoglobin levels (HbA1C);
- administering to a patient in need thereof a therapeutically effective amount of a composition comprising a compound represented by the structure (I)
Specification