Human protein tyrosine phosphatase inhibitors and methods of use
View Patent ↗The present disclosure relates to compounds effective as human protein tyrosine phosphatase beta (HPTP-β) inhibitors thereby regulating angiogenesis. The present disclosure further relates to compositions comprising said human protein tyrosine phosphatase beta (HPTP-β) inhibitors, and to methods for regulating angiogenesis.
1. A compound of the formula:
wherein:
R 6 is a unit chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, C 3 -C 6 branched, or C 3 -C 6 cyclic alkyl;
iii) substituted or unsubstituted phenyl; or
iv) substituted or unsubstituted heteroaryl;
said substitutions are chosen from methyl, ethyl, isopropyl, chloro and —SO 2 R 7 ;
R 7 is C 1 -C 4 linear, C 3 -C 4 branched, or C 3 -C 4 cyclic alkyl, or substituted or unsubstituted phenyl;
R 3 is hydrogen or methyl;
R 1 is chosen from:
i) hydrogen;
ii) C 1 -C 6 linear or C 3 -C 6 branched alkyl;
iii) benzyl; or
a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein R 6 is substituted or unsubstituted heteroaryl chosen from thien-2-yl, thien-3-yl, furan-2-yl, furan-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, pyridin-2-yl, pyridin-3-yl, or pyridin-4-yl.
3. The compound according to claim 2 , of the formula chosen from:
4. The compound according to claim 1 , chosen from:
(4((S)-2-((S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido)-2-(thiazol-4-yl)-ethyl)phenyl)sulfamic acid;
(4((S)-2-((S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido)-2-(2-methylthiazol-4-yl)-ethyl)phenyl)sulfamic acid;
(4((S)-2-((S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido)-2-(2-ethylthiazol-4-yl)-ethyl)phenyl)sulfamic acid;
(4((S)-2-((S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido)-2-(2-cyclopropyl-thiazol-4-yl)-ethyl)phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido]-2-[2-(thiophen-2-yl)thiazol-4-yl]ethyl}phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido]-2-[2-(thiophen-3-yl)thiazol-4-yl]ethyl}phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido]-2-[2-(3-chloro-thiophen-2-yl)thiazol-4-yl]ethyl}phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido]-2-[2-(3-methyl-thiophen-2-yl)thiazol-4-yl]ethyl}phenyl)sulfamic acid;
(4-((S)-2-((S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido)-2-(2-(5-(pyridin-2-yl)thiophen-2-yl)thiazol-4-yl)ethyl)phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido]-2-[2-(furan-2-yl)thiazol-4-yl]ethyl}phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido]-2-[2-(2-methyl-pyridin-5-yl)thiazol-4-yl]ethyl}phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido]-2-[2-phenylthiazol-4-yl]ethyl}phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-3-phenylpropanamido]-2-[2-(((4-chlorophenyl)sulfonyl)methyl)thiazol-4-yl]ethyl}phenyl)sulfamic acid;
(4-{(S)-2-[(S)-2-((methoxycarbonyl)amino)-4-methylpentanamido]-2-[2-(thiophen-2-yl)thiazol-4-yl]ethyl}phenyl)sulfamic acid
4-{(S)-2-[(S)-2-((Methoxycarbonyl)(methyl)amino)-3-phenylpropanamido]-2-(2-ethylthiazol-4-yl)ethyl}phenylsulfamic acid; and
4-{(S)-2-[(S)-2-((Methoxycarbonyl)(methyl)amino)-3-phenylpropionamido]-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl}phenylsulfamic acid.