Methods for treating vascular leak syndrome

1. 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:

R 2 , R 3 , and R 4 are each independently:

i) hydrogen;

ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;

iii) substituted or unsubstituted C 2 -C 6 linear, branched, or cyclic alkenyl;

iv) substituted or unsubstituted C 2 -C 6 linear or branched alkynyl;

v) substituted or unsubstituted C 6 or C 10 aryl;

vi) substituted or unsubstituted C 1 -C 9 heteroaryl;

vii) substituted or unsubstituted C 1 -C 9 heterocyclic; or

viii) R 2 and R 3 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 -R 1

R 1 is chosen from:

i) hydrogen;

ii) hydroxyl;

iii) amino;

iv) substituted or unsubstituted C 1 -C 6 linear, branched or cyclic alkyl;

v) substituted or unsubstituted C 1 -C 6 linear, branched or cyclic alkoxy;

vi) substituted or unsubstituted C 6 or C 10 aryl;

vii) substituted or unsubstituted C 1 -C 9 heterocyclic rings; or

viii) substituted or unsubstituted C 1 -C 9 heteroaryl rings;

L is a linking unit having the formula:

-[Q] y [C(R 5a R 5b )] x [Q 1 ] z [C(R 6a R 6b )] w —

Q and Q 1 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) —SO 2 —;

xii) —C(═NH)—;

xiii) —C(═NH)NH—;

xiv) —NHC(═NH)—; or

xv) —NHC(═NH)NH—;

R 5a and R 5b are each independently:

i) hydrogen;

ii) hydroxy;

iii) halogen;

iv) C 1 -C 6 substituted or unsubstituted linear or branched alkyl; or

v) a unit having the formula:

—[C(R 7a R 7b )] t R 8

R 7a and R 7b are each independently:

i) hydrogen; or

ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;

R 8 is:

i) hydrogen;

ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;

iii) substituted or unsubstituted C 6 or C 10 aryl;

iv) substituted or unsubstituted C 1 -C 9 heteroaryl; or

v) substituted or unsubstituted C 1 -C 9 heterocyclic;

R 6a and R 6b are each independently:

i) hydrogen; or

ii) C 1 -C 4 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.

2. The method according to claim 1 , wherein the compound has the formula:

or

a pharmaceutically acceptable salts thereof.