METHODS FOR TREATING VASCULAR LEAK SYNDROME

摘要

Disclosed are methods for treating Vascular Leak Syndrome. Further disclosed are methods for treating vascular leakage due to inflammatory diseases, inter alia, sepsis, lupus, inflammatory bowel disease. Yet further disclosed are methods for treating renal cell carcinoma and melanoma. Still further disclosed are methods for reducing metastasis of malignant cells and/or preventing the proliferation of carcinoma cells via spreading due to vascular leakage.

主权项

1. A method for providing vascular stabilization in a subject infected with a pathogen, comprising administering to the subject one or more compounds having the formula: wherein R is a substituted or unsubstituted thiazolyl unit having the formula: R2, R3, and R4 are each independently: i) hydrogen; ii) substituted or unsubstituted C1-C6 linear, branched, or cyclic alkyl; iii) substituted or unsubstituted C2-C6 linear, branched, or cyclic alkenyl; iv) substituted or unsubstituted C2-C6 linear or branched alkynyl; v) substituted or unsubstituted C6 or C10 aryl; vi) substituted or unsubstituted C1-C9 heteroaryl; vii) substituted or unsubstituted C1-C9 heterocyclic; or viii) R2 and R3 can be taken together to form a saturated or unsaturated ring having from 5 to 7 atoms; wherein from 1 to 3 atoms can optionally be heteroatoms chosen from oxygen, nitrogen, and sulfur; Z is a unit having the formula:
-(L)n-R1 R1 is chosen from: i) hydrogen; ii) hydroxyl; iii) amino; iv) substituted or unsubstituted C1-C6 linear, branched or cyclic alkyl; v) substituted or unsubstituted C1-C6 linear, branched or cyclic alkoxy; vi) substituted or unsubstituted C6 or C10 aryl; vii) substituted or unsubstituted C1-C9 heterocyclic rings; or viii) substituted or unsubstituted C1-C9 heteroaryl rings; L is a linking unit having the formula:
-[Q]y[C(R5aR5b)]x[Q1]z[C(R6aR6b)]w— Q and Q1 are each independently: i) —C(O)—; ii) —NH—; iii) —C(O)NH—; iv) —NHC(O)—; v) —NHC(O)NH—; vi) —NHC(O)O—; vii) —C(O)O—; viii) —C(O)NHC(O)—; ix) —O—; x) —S—; xi) —SO2—; xii) —C(═NH)—; xiii) —C(═NH)NH—; xiv) —NHC(═NH)—; or xv) —NHC(═NH)NH—; R5a and R5b are each independently: i) hydrogen; ii) hydroxy; iii) halogen; iv) C1-C6 substituted or unsubstituted linear or branched alkyl; or v) a unit having the formula:
—[C(R7aR7b)]tR8 R7a and R7b are each independently: i) hydrogen; or ii) substituted or unsubstituted C1-C6 linear, branched, or cyclic alkyl; R8 is: i) hydrogen; ii) substituted or unsubstituted C1-C6 linear, branched, or cyclic alkyl; iii) substituted or unsubstituted C6 or C10 aryl; iv) substituted or unsubstituted C1-C9 heteroaryl; or v) substituted or unsubstituted C1-C9 heterocyclic; R6a and R6b are each independently: i) hydrogen; or ii) C1-C4 linear or branched alkyl; the index n is 0 or 1; the indices t, w and x are each independently from 0 to 4; the indices y and z are each independently 0 or 1; or a pharmaceutically acceptable salt thereof.