Fatty acid acylated salicylates and their uses
Inventors
Vu, Chi B. • Bemis, Jean E. • Jirousek, Michael R. • MILNE, JILL C. • Smith, Jesse J.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-9708245-B2
Publication Date
2017-07-18
Expiration Date
Abstract
The invention relates to fatty acid acylated salicylate derivatives; compositions comprising an effective amount of a fatty acid acylated salicylate derivative; and methods for treating or preventing an inflammatory disorder comprising the administration of an effective amount of a fatty acid acylated salicylate derivative.
Core Innovation
The invention relates to compounds of Formula I, including pharmaceutically acceptable salts, enantiomers, stereoisomers, hydrates, solvates, and prodrugs. The compounds are defined by multiple independently selected substituents R1, R2, R3, and R4, together with structural variables W1, W2, W3, Q, a, b, c, d, L, m, n, o, p, q, r, s, t, w, Z, e, R7, R, and T. Optional bond presence between the phenolic oxygen and the methylene-containing substituent a, or between substituent a and the carbon of the methylene-containing substituent a, is tied to whether Q is null or not null.
W1 and W2 are each independently NH, while W3 is null or —N(R)—. The linker L is selected from —O—, —S—, or —S—S—, with m selected from 0, 1, 2, or 3. The variables a, b, c, and d, as well as n, o, p, q, r, s, t, w, Q, Z, e, R7, R, and T, are each constrained by explicit allowed values within the Formula I framework.
The disclosure further refers to related Formula II, Formula III, Formula IIIa, Formula IIIb, Formula IIIc, Formula IIId, Formula IIIe, Formula IIIf, Formula IIIg, and Formula I2d-type embodiments, with illustrative compound structures and shared variable definitions. The described compound space includes structural variants using the same parameter set and conditional relationships, including the proviso that when w is 0 then W1 is NH, and Q is selected from null, C(O)CH3, or Z.
Claims Coverage
The consolidated claim coverage centers on one independent claim defining a Formula I compound, with dependent claims narrowing structural variables, linker selections, and parameter values. In total, the consolidated coverage includes one principal inventive feature set built around the Formula I scaffold and its conditional connectivity rules.
Formula I compound with defined substituent set
A compound of Formula I, or a pharmaceutically acceptable salt, enantiomer, or stereoisomer thereof, wherein R1, R2, R3, and R4 are each independently selected from the specified group and W1 and W2 are each independently NH.
Optional bond controls Q nullity
An optional bond between the phenolic oxygen and the methylene-containing substituent a requires Q to be null, and an optional bond between substituent a and the carbon of the methylene-containing substituent a requires Q not to be null.
Defined linker and parameter constraints
L is selected from —O—, —S—, or —S—S—; m is 0, 1, 2, or 3; a, b, c, and d are independently selected from the stated groups; and n, o, p, q, r, s, t, w, Z, e, R7, R, W3, Q, and T are each constrained to the listed allowed values.
Conditional proviso linking w and W1
When w is 0, then W1 is NH.
The claim coverage is directed to a Formula I compound family defined by explicit substituent selections, linker types, and conditional optional-bond rules tied to Q, with additional constraints on integer parameters and heteroatom variables. The independent scope is the Formula I scaffold, and dependent refinements further restrict the permitted structural configurations.
Stated Advantages
Low peripheral toxicity.
Upregulation of anti-inflammatory pathways.
Downregulation of proinflammatory pathways, including NFκB-capable inflammatory cells.
NFκB inhibition.
TNFα inhibitory activity.
Treatment of inflammation and inflammatory diseases.
Documented Applications
Treating inflammation associated with a metabolic disorder, where the inflammation is associated with inflammatory bowel disease, muscular dystrophy, cachexia, Crohn's disease, or Type II diabetes.
A pharmaceutical composition including a compound of claim 1 together with a pharmaceutically acceptable carrier.
An inflammatory activity assay framework involving NFκB and TNFα to assess inflammatory activity of the compounds.
Interested in licensing this patent?