Methods for treating vascular leak syndrome

A method for determining the course of treatment for a subject suffering from vascular leak syndrome, comprising:

• a) administering to a subject an effective amount of 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;
• and
• b) monitoring the blood plasma level of angiopoietin-2 in the subject;
• wherein administering of the one or more compounds stops when the level of angiopoietin-2 in the blood plasma of the subject is from about 1 ng/mL to about 2 ng/mL.