Patent ID: 8399512
Filing Date: 2013-03-19
Classification: A61K,A61P,C07D

Abstract:
1. A conjugate of Formula I or a pharmaceutically acceptable salt thereof: wherein the fumagillin analog is a fumagillin core structure which demonstrates MetAP-2 inhibition along with a chemical spacer moiety that allows the fumagillin core structure to be covalently attached through X at the C-6 of the fumagillin core structure to an OH of the polyal, wherein the fumagillin core structure has the formula II: wherein X is O, S(═O) R is (2S,3R)-2-methyl-3-(3-methylbut-2-enyl)oxirane, 2-methylhepta-2,5-diene, (2R,3S)-2-isopentyl-3-methyloxirane, 6-methylhept-2-ene, (Z)-acetaldehyde O-benzyl oxime, C M is O, or q is 0, 1, or 2; wherein the compound is optionally substituted at C-7 and C-8, independently, with C m is an integer from 1 to 40; and polyal has the structure wherein n is an integer from 1 to 3000; wherein the fumagillin analog is directly or indirectly attached to R wherein for each occurrence of the n bracketed structure, either one of R each of R R each of R L is a bond, —CH(OH)—, —NH—, —O—, —S—, —SO—, —SO the dashed line between the carbon atoms at positions a and b represents a carbon-carbon single bond or a carbon-carbon double bond; and the carbon atoms adjacent to L can be individually optionally substituted with OH, halogen, CN, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, C1-C3 fluorinated alkyl, NO or wherein Linker is an oxalic, malonic, succinic, glutaric, adipic, pimelic, suberic, azelaic, sebacic, phthalic, isophthalic, terephthalic, diglycolic acid, tartaric, glutamic, fumaric, or aspartic moiety.