HUMAN PROTEIN TYROSINE PHOSPHATASE INHIBITORS AND METHODS OF USE
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:
R 4 is chosen from:
i) C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
ii) phenyl; or
iii) thiophen-2-yl;
R 1 is:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
iii) substituted or unsubstituted phenyl; or
iv) substituted or unsubstituted heteroaryl;
wherein said substitutions are chosen from C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl, C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkoxy, halogen, and hydroxyl; or two substitutions can be taken together to form a 5-member to 7-member fused ring containing from 1 to 3 heteroatoms chosen from oxygen, sulfur, and nitrogen;
the index x is from 1 or 2; or
a pharmaceutically acceptable salt thereof.
2 . The compound according to claim 1 , wherein R 4 is thiophen-2-yl.
3 . The compound according to claim 1 , wherein R 1 is chosen from 2-fluorophenyl, 3-fluorophenyl, 2,3-difluorophenyl, 2-chlorophenyl, 3-chloropenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2,3-dimethoxyphenyl, and 3,4-dimethoxyphenyl.
4 . The compound according to claim 1 , wherein R 1 is chosen from 3-methyl-1,2,4-oxadiazol-5-yl or 4-ethyl-2,3-dioxopiperazin-1-yl.
5 . The compound according to claim 1 , chosen from
4-((S)-2-(2-(3-Chlorophenyl)acetamido)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)-phenylsulfamic acid;
4-((S)-2-(2-(3-Methoxyphenyl)acetamido)-2-(2-(thiophene2-yl)thiazol-4-yl)ethyl)-phenylsulfamic acid;
4-{(S)-2-(3-Phenylpropanamido)-2-[2-(thiophene2-yl)thiazol-4-yl]ethyl}phenyl-sulfamic acid;
4-{(S)-2-(3-(3-Chlorophenyl)propanamido)-2-[2-(thiophene2-yl)thiazol-4-yl]ethyl}phenylsulfamic acid;
4-{(S)-2-[2-(3-Fluorophenyl)acetamido]-2-[2-(thiophene-2-yl)thiazol-4-yl]ethyl}phenylsulfamic acid;
(S)-4-{2-[2-(3-Methyl-1,2,4-oxadiazol-5-yl)acetamido]-2-(2-phenylthiazol-4-yl)ethyl}phenylsulfamic acid;
4-{(S)-2-[2-(4-Ethyl-2,3-dioxopiperazin-1-yl)acetamido]-2-[2-(thiophene-2-yl)thiazol-4-yl]ethyl}phenylsulfamic acid
(S)-4-(2-(4-(Thiophen-2-yl)thiazol-2-yl)-2-(3-(3-chlorophenyl)propanamido)-ethyl)phenyl-sulfamic acid; and
(S)-4-(2-(2-(2-Chlorophenyl)acetamido)-2-(4-(thiophen-2-yl)thiazol-2-yl)ethyl)-phenylsulfamic acid.
6 . The compound according to claim 1 , wherein the compounds are salts comprising cations chosen from ammonium, sodium, lithium, potassium, calcium, magnesium, and bismuth.
7 . A compound of the formula:
wherein:
R 2 and R 3 are each independently chosen from:
i) C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
ii) phenyl; or
iii) thiophen-2-yl;
R 1 is:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
iii) substituted or unsubstituted phenyl; or
iv) substituted or unsubstituted heteroaryl;
wherein said substitutions are chosen from C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl, C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkoxy, halogen, and hydroxyl; or two substitutions can be taken together to form a 5-member to 7-member fused ring containing from 1 to 3 heteroatoms chosen from oxygen, sulfur, and nitrogen;
R 6a and R 6b are each independently:
i) hydrogen;
ii) phenyl or substituted phenyl; or
iii) heteroaryl or substituted heteroaryl;
the index x is from 1 or 2; or
a pharmaceutically acceptable salt thereof.
8 . The compound according to claim 7 , wherein R 2 is ethyl.
9 . The compound according to claim 7 , wherein R 2 is thiophen-2-yl.
10 . The compound according to claim 7 , wherein R 1 is chosen from phenyl, 2-fluorophenyl, 3-fluorophenyl, 2,3-difluorophenyl, 3,4-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2,3-dimethoxyphenyl, and 3,4-dimethoxyphenyl.
11 . The compound according to claim 10 , wherein the index x is equal to 1.
12 . The compound according to claim 10 , wherein the index x is equal to 2.
13 . The compound according to claim 7 , chosen from:
{4-[2-(S)-(4-Ethylthiazol-2-yl)-2-(2-phenylacetylamido)ethyl]phenyl}sulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(2-(2-fluorophenyl)acetamido)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(2-(3-fluorophenyl)acetamido)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(2-(2,3-Difluorophenyl)acetamido)-2-(4-ethylthiazol-2-yl)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(2-(3,4-Difluorophenyl)acetamido)-2-(4-ethylthiazol-2-yl)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(2-(2-Chlorophenyl)acetamido)-2-(4-ethylthiazol-2-yl)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(2-(3-Chlorophenyl)acetamido)-2-(4-ethylthiazol-2-yl)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(2-(3-hydroxyphenyl)acetamido)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(2-(2-methoxyphenyl)acetamido)ethyl)phenyl-sulfamic acid;
(S)-4-{2-(4-Ethylthiazol-2-yl)-2-[2-(3-methoxyphenyl)acetamido]ethyl}phenyl-sulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(3-phenylpropanamido)ethyl)phenylsulfamic acid;
(S)-4-(2-(2-(3,4-Dimethoxyphenyl)acetamido)-2-(4-ethylthiazol-2-yl)ethyl)-phenylsulfamic acid;
(S)-4-(2-(2-(2,3-Dimethoxyphenyl)acetamido)-2-(4-ethylthiazol-2-yl)ethyl)-phenylsulfamic acid;
(S)-4-(2-(3-(3-Chlorophenyl)propanamido)-2-(4-ethylthiazol-2-yl)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(3-(2-methoxyphenyl)propanamido)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(3-(3-methoxyphenyl)propanamido)ethyl)phenyl-sulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(3-(4-methoxyphenyl)propanamido)ethyl)phenyl-sulfamic acid;
(S)-4-{2-[2-(4-Ethyl-2,3-dioxopiperazin-1-yl)acetamido]-2-(4-ethylthiazol-2-yl)ethyl}phenylsulfamic acid;
(S)-4-{2-(4-Ethylthiazol-2-yl)-2-[2-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)acetamido]ethyl}phenylsulfamic acid;
(S)-4-{2-[2-(2,5-Dimethylthiazol-4-yl)acetamido]-2-(4-ethylthiazol-2-yl)ethyl}-phenylsulfamic acid;
(S)-4-{2-[2-(2,4-Dimethylthiazol-5-yl)acetamido]-2-(4-methylthiazol-2-yl)ethyl}phenylsulfamic acid;
(S)-4-{2-(4-Ethylthiazol-2-yl)-2-[3-(thiazol-2-yl)propanamido]ethyl}phenyl-sulfamic acid; and
(S)-4-{2-(4-Ethylthiazol-2-yl)-2-[2-(4-ethylthiazol-2-yl)acetamido]ethyl}phenyl-sulfamic acid;
(S)-4-(2-(4-(thiophen-2-yl)thiazol-2-yl)-2-(3-(3-chlorophenyl)propanamido)-ethyl)phenyl-sulfamic acid;
(S)-4-(2-(2-(2-Chlorophenyl)acetamido)-2-(4-(thiophen-2-yl)thiazol-2-yl)ethyl)-phenylsulfamic acid; and
(S)-4-(2-(2-(3-Fluorophenyl)acetamido)-2-(4-(thiophen-2-yl)thiazol-2-yl)ethyl)-phenylsulfamic acid.
14 . The compound according to claim 7 , chosen from:
(S)-4-(2-(2,3-Diphenylpropanamido)-2-(4-ethylthiazol-2-yl)ethyl)-phenylsulfamic acid;
(S)-4-{2-(4-Ethylthiazol-2-yl)-2-[2-(2-methoxyphenyl)-3-phenylpropanamido]-ethyl}phenylsulfamic acid;
(S)-4-{2-(4-Ethylthiazol-2-yl)-2-[2-(3-fluorophenyl)-3-phenylpropanamido]-ethyl}phenylsulfamic acid;
(4-((2S)-2-(4-Ethylthiazol-2-yl)-2-(2-(3-methoxyphenyl)-3-phenylpropanamido)-ethyl)phenyl)sulfamic acid; and
4-{(S)-2-(4-Ethylthiazol-2-yl)-2-[2-(3-methyl-1,2,4-oxadiazol-5-yl)-3-phenyl-propanamido]ethyl}phenylsulfamic acid.
15 . The compound according to claim 7 , wherein the compounds are salts comprising cations chosen from ammonium, sodium, lithium, potassium, calcium, magnesium, and bismuth.
16 . A compound of the formula:
wherein:
R 2 and R 3 are each independently chosen from:
i) C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
ii) phenyl; or
iii) thiophen-2-yl;
R 1 is:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
iii) substituted or unsubstituted phenyl; or
iv) substituted or unsubstituted heteroaryl;
wherein said substitutions are chosen from C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl, C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkoxy, halogen, and hydroxyl; or two substitutions can be taken together to form a 5-member to 7-member fused ring containing from 1 to 3 heteroatoms chosen from oxygen, sulfur, and nitrogen;
R 7a and R 7b are each independently:
i) hydrogen;
ii) phenyl or substituted phenyl; or
iii) heteroaryl or substituted heteroaryl;
the index xy is from 1 or 2; or
a pharmaceutically acceptable salt thereof.
17 . The compound according to claim 16 , chosen from:
(S)-4-[2-(4-Ethylthiazol-2-yl)-2-(4-oxo-4-phenylbutanamido)ethyl]-phenylsulfamic acid;
(S)-4-(2-(4-Ethylthiazol-2-yl)-2-(5-methyl-4-oxohexanamido)ethyl)phenyl-sulfamic acid;
(S)-4-{2-[4-(3,4-Dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-4-oxobutanamido]-2-(4-ethylthiazol-2-yl)ethyl}phenylsulfamic acid;
(S)-4-{2-[4-(2,3-Dimethoxyphenyl)-4-oxobutanamido]-2-(4-ethylthiazol-2-yl)ethyl}phenylsulfamic acid;
(S)-4-{2-(4-Ethylthiazol-2-yl)-2-[4-oxo-4-(pyridin-2-yl)butanamido]ethyl}-phenylsulfamic acid;
(S)-4-{2-[4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4-oxobutanamido]-2-(4-ethylthiazol-2-yl)ethyl}phenylsulfamic acid;
(S)-4-[2-(4-tert-butoxy-4-oxobutanamido)-2-(4-ethylthiazol-2-yl)ethyl]phenyl-sulfamic acid; and
(S)-4-[2-(4-ethoxy-4-oxobutanamido)-2-(4-ethylthiazol-2-yl)ethyl]phenylsulfamic acid.
18 . The compound according to claim 16 , wherein the compounds are salts comprising cations chosen from ammonium, sodium, lithium, potassium, calcium, magnesium, and bismuth.
19 . A compound of the formula:
wherein:
R 4 is chosen from:
i) C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
ii) phenyl; or
iii) thiophen-2-yl;
R 1 is:
i) substituted or unsubstituted C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
ii) substituted or unsubstituted phenyl; or
iii) substituted or unsubstituted heteroaryl;
wherein said substitutions are chosen from C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl, C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkoxy, halogen, phenyl or substituted phenyl; said phenyl substitutions chosen from methyl, ethyl, methoxy, —CO 2 CH 3 , —NHCOR 16 ; R 16 is methyl or substituted phenyl, wherein the substitutions are one or more halogen; or two substitutions can be taken together to form a 5-member to 7-member fused ring containing from 1 to 3 heteroatoms chosen from oxygen, sulfur, and nitrogen; or
a pharmaceutically acceptable salt thereof.
20 . The compound according to claim 19 , wherein R 1 is phenyl substituted C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl.
21 . The compound according to claim 20 , wherein the phenyl substitution can be further substituted by methyl, ethyl, methoxy, —CO 2 CH 3 , —NHCOR 16 ; R 16 is phenyl substituted by halogen.
22 . The compound according to claim 19 , chosen from:
(S)-(4-(2-(Phenylmethylsulfonamido)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)phenyl)sulfamic acid;
{4-(S)-[2-Phenylmethanesulfonylamino-2-(2-ethylthiazol-4-yl)ethyl]phenyl}-sulfamic acid;
{4-(S)-[2-(3-Methoxyphenyl)methanesulfonylamino-2-(2-ethylthiazol-4-yl)ethyl]phenyl}sulfamic acid;
(S)-4-{[1-(2-Ethylthiazol-4-yl)-2-(4-sulfoaminophenyl)ethylsulfamoyl]methyl}-benzoic acid methyl ester;
(S)-4-[2-(2-Ethylthiazol-4-yl)-2-(1-methyl-1H-imidazol-4-sulfonamido)ethyl]-phenylsulfamic acid;
4-{(S)-2-[2-(Thiophen-2-yl)thiazol-4-yl]-2-(2,2,2-trifluoroethylsulfonamido)-ethyl}phenylsulfamic acid;
{4-(S)-[3-(Phenylpropanesulfonylamino)-2-(2thiophen-2-ylthiazol-4-yl)ethyl]-phenyl}sulfamic acid;
(S)-{4-[2-(4-Methyl-3,4-dihydro-2H-benzo[1,4]oxazine-7-sulfonylamino)-2-(2-thiophen-2-ylthiazol-4-yl)ethyl]phenyl}sulfamic acid;
4-{(S)-2-(4-acetamidophenylsulfonamido)-2-[2-(thiophen-2-yl)thiazol-4-yl]ethyl}phenylsulfamic acid;
(S)-(4-(2-(2-(4-(Methoxycarbonyl)phenyl)methylsulfonamido)-2-(2-ethylthiazol-4-yl)ethyl)phenyl)sulfamic acid; and
(S)-(4-(2-(2-Phenylethanesulfonylamino)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)-phenyl)sulfamic acid.
23 . The compound according to claim 19 , wherein the compounds are salts comprising cations chosen from ammonium, sodium, lithium, potassium, calcium, magnesium, and bismuth.
24 . A compound of the formula:
wherein:
R 1 is substituted or unsubstituted heteroaryl;
wherein said substitutions are chosen from C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl, C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkoxy, halogen, —CONHCH 2 CO 2 CH 3 , phenyl or substituted phenyl; said phenyl substitutions chosen from methyl, ethyl, methoxy, —CO 2 CH 3 , —NHCOR 16 ; R 16 is methyl, substituted phenyl, wherein the substitutions are one or more halogen; or two substitutions can be taken together to form a 5-member to 7-member fused ring containing from 1 to 3 heteroatoms chosen from oxygen, sulfur, and nitrogen; or
R 4 is chosen from:
i) C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl;
ii) phenyl; or
iii) thiophen-2-yl; or
a pharmaceutically acceptable salt thereof.
25 . The compound according to claim 24 , wherein R 1 is a substituted or unsubstituted heteroaryl unit chosen from:
i) 1,2,3,4-tetrazol-1-yl and 1,2,3,4-tetrazol-5-yl having the respective formulae:
ii) [1,2,3]triazol-4-yl, [1,2,3]triazol-5-yl, [1,2,4]triazol-4-yl, and [1,2,4]triazol-5-yl having the respective formulae:
iii) imidazol-2-yl and imidazol-4-yl having the respective formulae:
iv) pyrrol-2-yl and pyrrol-3-yl having the respective formulae:
v) oxazol-2-yl, oxazol-4-yl, and oxazol-5-yl having the respective formulae:
vi) isoxazol-3-yl, isoxazol-4-yl, and isoxazol-5-yl having the respective formulae:
vii) [1,2,4]oxadiazol-3-yl and [1,2,4]oxadiazol-5-yl having the respective formulae:
viii) [1,3,4]oxadiazol-2-yl having the formula:
ix) furan-2-yl and furan-3-yl having the respective formulae:
x) thiophene-2-yl and thiophene-3-yl having the respective formulae:
xi) isothiazol-3-yl, isothiazol-4-yl and isothiazol-5-yl having the respective formulae:
xii) thiazol-2-yl, thiazol-4-yl and thiazol-5-yl having the respective formulae:
and
xiii) [1,2,4]thiadiazol-3-yl and [1,2,4]thiadiazol-5-yl having the respective formulae:
said heteroaryl unit substitutions chosen from:
i) C 1 -C 6 linear, branched, and cyclic alkyl;
ii) substituted or unsubstituted phenyl and benzyl;
iii) substituted of unsubstituted heteroaryl;
iv) —C(O)R 9 ; and
v) —NHC(O)R 9 ;
R 9 is C 1 -C 6 linear and branched alkyl; C 1 -C 6 linear and branched alkoxy; or —NHCH 2 C(O)R 10 ; R 10 is chosen from hydrogen, methyl, ethyl, and tert-butyl;
26 . The compound according to claim 25 , wherein R 1 is substituted by an alkyl unit chosen from methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, and tert-butyl.
27 . The compound according to claim 25 , wherein R 1 is substituted by substituted or unsubstituted phenyl and benzyl, said phenyl and benzyl substitutions are chosen from one or more:
i) halogen;
ii) C 1 -C 3 alkyl;
iii) C 1 -C 3 alkoxy;
iv) —CO 2 R 11 ; and
v) —NHCOR 12 ;
wherein R 11 and R 12 are each independently hydrogen, methyl, or ethyl.
28 . The compound according to claim 25 , wherein R 1 is substituted by a carboxy unit having the formula —C(O)R 9 ; R 9 is chosen from methyl, methoxy, ethyl, and ethoxy.
29 . The compound according to claim 25 , wherein R 1 is substituted by an amide unit having the formula —NHC(O)R 9 ; R 9 is chosen from methyl, methoxy, ethyl, ethoxy, tert-butyl, and tert-butoxy.
30 . The compound according to claim 25 , wherein R 1 is chosen from 4-(methoxy-carbonyl)thiazol-5-yl, 4-[(2-methoxy-2-oxoethyl)carbamoyl]thiazol-5-yl, 5-[1-N-(2-methoxy-2-oxoethyl)-1-H-indol-3-yl]oxazol-2-yl, 5-(2-methoxyphenyl)oxazol-2-yl, 5-[(5)-1-(tert-butoxycarbonyl)-2-phenylethyl]oxazol-2-yl, 5-[4-(methyl-carboxy)phenyl]oxazol-2-yl, 5-(3-methoxybenzyl)oxazol-2-yl, 5-(4-phenyl)-oxazol-2-yl, 5-(2-methoxyphenyl)thiazol-2-yl, 5-(3-methoxyphenyl)thiazol-2-yl, 5-(4-fluorophenyl)thiazol-2-yl, 5-(2,4-difluorophenyl)thiazol-2-yl, 5-(3-methoxy-benzyl)thiazol-2-yl, 4-(3-methoxyphenyl)thiazol-2-yl, and 4-(4-fluorophenyl)-thiazol-2-yl.
31 . The compound according to claim 24 , chosen from:
(S)-4-(2-(5-Methyl-1,3,4-thiadiazol-2-ylamino)-2-(2-phenylthiazol-4-yl)ethyl)-phenylsulfamic acid;
4-{(S)-2-[4-(2-Methoxyphenyl)thiazol-2-ylamino)-2-[2-(thiophen-2-yl)thiazol-4-yl]ethyl}phenylsulfamic acid;
4-{(S)-2-[5-(3-Methoxyphenyl)oxazol-2-ylamino]-2-(2-phenylthiazole-4-yl)ethyl}phenylsulfamic acid;
(S)-4-(2-(5-Phenyl-1,3,4-thiadiazol-2-ylamino)-2-(2-phenylthiazol-4-yl)ethyl)-phenylsulfamic acid;
4-((S)-2-(5-Propyl-1,3,4-thiadiazol-2-ylamino)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)phenylsulfamic acid;
4-((S)-2-(5-Benzyl-1,3,4-thiadiazol-2-ylamino)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)phenylsulfamic acid;
4-((S)-2-(5-(Naphthalen-1-ylmethyl)-1,3,4-thiadiazol-2-ylamino)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)phenylsulfamic acid;
4-((S)-2-(5-((Methoxycarbonyl)methyl)-1,3,4-thiadiazol-2-ylamino)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)phenylsulfamic acid;
4-((S)-2-(5-((2-Methylthiazol-4-yl)methyl)-1,3,4-thiadiazol-2-ylamino)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)phenylsulfamic acid;
4-{(S)-2-[4-(2,4-Difluorophenyl)thiazol-2-ylamino]-2-[2-(thiophen-2-yl)thiazol-4-yl)ethyl}phenylsulfamic acid;
(S)-4-{2-[4-(Ethoxycarbonyl)thiazol-2-ylamino]-2-(2-phenylthiazol-4-yl)ethyl}phenylsulfamic acid;
(S)-4-{2-[4-(2-Ethoxy-2-oxoethyl)thiazol-2-ylamino]-2-(2-phenylthiazol-4-yl)ethyl}phenylsulfamic acid;
(S)-4-{2-[4-(4-acetamidophenyl)thiazol-2-ylamino]-2-(2-phenylthiazol-4-yl)ethyl}phenylsulfamic acid;
(S)-4-[2-(4-phenylthiazol-2-ylamino)-2-(2-phenylthiazol-4-yl)ethyl]phenyl-sulfamic acid;
(S)-4-{2-[4-(4-(methoxycarbonyl)phenyl)thiazol-2-ylamino]-2-(2-phenylthiazol-4-yl)ethyl}phenylsulfamic acid;
4-{(S)-2-[4-(Ethoxycarbonyl)thiazol-2-ylamino]-2-[2-(thiophen-2-yl)thiazol-4-yl]ethyl}phenylsulfamic acid;
(S)-4-[2-(4-(Methoxycarbonyl)thiazol-5-ylamino)-2-(2-phenylthiazole-4-yl)ethyl]phenylsulfamic acid;
(S)-4-[2-(4-(Methoxycarbonyl)thiazol-5-ylamino)-2-(2-phenylthiazole-4-yl)ethyl]phenylsulfamic acid;
(S)-4-{2-[5-(4-Acetamidophenyl)oxazol-2-ylamino]-2-(2-phenylthiazol-4-yl)ethyl}phenylsulfamic acid;
4-((S)-2-(5-(2,4-Difluorophenyl)oxazole-2-ylamino)-2-(2-phenylthiazole-4-yl)ethyl)phenylsulfamic acid;
4-{(S)-2-[5-(3-Methoxyphenyl)oxazol-2-ylamino]-2-[(2-thiophen-2-yl)thiazole-4-yl]ethyl}phenylsulfamic acid;
(S)-4-[2-(4,6-Dimethylpyrimidin-2-ylamino)-2-(2-methylthiazole-4-yl)ethyl]phenylsulfamic acid;
(S)-4-[2-(4-Hydroxy-6-methylpyrimidine-2-ylamino)-2-(2-methylthiazole-4-yl)ethyl]phenylsulfamic acid;
(S)-(4-(2-(5-((4-chlorobenzamido)methyl)thiophene-2-sulfonamino)-2-(2-(thiophen-2-yl)thiazol-4-yl)ethyl)phenyl)sulfamic acid; and
(S)-(4-(2-(2-ethylthiazol-4-yl)-2-((4-((2-methoxy-2-oxoethyl)carbamoyl)thiazol-5-yl)amino)ethyl)phenyl)sulfamic acid.
32 . A compound of the formula:
wherein:
R 1 is substituted or unsubstituted heteroaryl;
wherein said substitutions are chosen from C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl, C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkoxy, halogen, —CONHCH 2 CO 2 CH 3 , phenyl or substituted phenyl; said phenyl substitutions chosen from methyl, ethyl, methoxy, —CO 2 CH 3 , —NHCOR 16 ; R 16 is methyl, substituted phenyl, wherein the substitutions are one or more halogen; or two substitutions can be taken together to form a 5-member to 7-member fused ring containing from 1 to 3 heteroatoms chosen from oxygen, sulfur, and nitrogen;
R 2 is C 1 -C 4 linear, C 3 -C 4 branched or C 3 -C 4 cyclic alkyl; or
a pharmaceutically acceptable salt thereof.
33 . The compound according to claim 32 , wherein the compound is (S)-(4-(2-(4-cyclopropylthiazol-2-yl)-2-((5-(2,4-difluorophenyl)thiazol-2-yl)amino)ethyl)phenyl)sulfamic acid;
34 . A method for regulating angiogenesis in a human, comprising administering to a human a compound according to claim 1 .
35 . A method for regulating angiogenesis in a human, comprising administering to a human a compound according to claim 7 .
36 . A method for regulating angiogenesis in a human, comprising administering to a human a compound according to claim 16 .
37 . A method for regulating angiogenesis in a human, comprising administering to a human a compound according to claim 19 .
38 . A method for regulating angiogenesis in a human, comprising administering to a human a compound according to claim 24 .
39 . A method for inhibiting Human Protein Tyrosine Phosphatase-beta (HPTP-β) in a human, comprising administering to a human a compound according to claim 1 .
40 . A method for inhibiting Human Protein Tyrosine Phosphatase-beta (HPTP-β) in a human, comprising administering to a human a compound according to claim 7 .
41 . A method for inhibiting Human Protein Tyrosine Phosphatase-beta (HPTP-β) in a human, comprising administering to a human a compound according to claim 16 .
42 . A method for inhibiting Human Protein Tyrosine Phosphatase-beta (HPTP-β) in a human, comprising administering to a human a compound according to claim 19 .
43 . A method for inhibiting Human Protein Tyrosine Phosphatase-beta (HPTP-β) in a human, comprising administering to a human a compound according to claim 24 .