US2010016336A1PendingUtilityA1
Human protein tyrosine phosphatase inhibitors and methods of use
Est. expiryJun 27, 2026(expired)· nominal 20-yr term from priority
Inventors:Jeffrey Lyle GrayKande K. D. AmarasingheCynthia Monesa ClarkRyan Matthew NicholsMatthew B. Maier
A61P 9/04A61P 7/06A61P 9/10A61P 9/08A61P 43/00A61P 37/04A61P 9/00A61P 37/02A61P 31/18A61P 31/12A61P 31/00A61P 29/00A61P 27/10A61P 31/04A61P 33/02A61P 31/16A61P 35/00A61P 27/02A61P 17/06A61P 21/00A61P 19/08A61P 1/04A61P 19/10A61P 17/02A61P 19/02A61K 31/427A61K 9/0019A61K 31/428C07D 277/28C07D 277/60C07D 417/04A61K 31/426C07D 277/64C07D 277/30A61K 31/497A61K 31/425Y02A50/30
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Claims
Abstract
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.
Claims
exact text as granted — not AI-modified1 . A compound having the formula:
wherein R is a substituted or unsubstituted thiazolyl unit having the formula:
R 4 and R 5 are each independently chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl;
iv) substituted or unsubstituted heteroaryl; or
R 4 and R 5 can be taken together to form a saturated or unsaturated ring having from 5 to 7 atoms;
said substitutions are independently chosen from one or more C 1 -C 6 linear, branched, or cyclic alkyl, halogen, hydroxyl, or cyano units;
R 6 is a unit chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl; and
iv) substituted or unsubstituted heteroaryl;
R 1 is chosen from:
i) hydrogen;
ii) C 1 -C 6 linear or branched alkyl;
iii) substituted or unsubstituted phenyl; or
iv) substituted or unsubstituted benzyl;
R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 3 is hydrogen or C 1 -C 4 linear or branched alkyl.
2 . A compound according to claim 1 , wherein R has the formula:
3 . A compound according to claim 2 , wherein R 4 and R 5 are each hydrogen.
4 . A compound according to claim 2 , wherein R 5 is hydrogen and R 4 is substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl.
5 . A compound according to claim 4 , wherein R 4 is chosen from methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, cyclopropyl, n-hexyl, and cyclohexyl.
6 . A compound according to claim 4 , wherein R 4 is chosen from units having the formulae —CH 2 F, —CHF 2 , —CF 3 , —CH 2 CF 3 , —CH 2 CH 2 CF 3 , —CH 2 Cl, —CH 2 OH, —CH 2 OCH 3 , —CH 2 CH 2 OH, —CH 2 CH 2 OCH 3 , —CH 2 NH 2 , —CH 2 NHCH 3 , —CH 2 N(CH 3 ) 2 , and —CH 2 NH(CH 2 CH 3 ).
7 . A compound according to claim 4 , wherein R 4 is 2,2-difluorocyclopropyl, 2-methoxycyclohexyl, or 4-chlorocyclohexyl.
8 . A compound according to claim 2 , wherein R 5 is hydrogen and R 4 is substituted or unsubstituted substituted or unsubstituted phenyl.
9 . A compound according to claim 8 , wherein R 4 is chosen from phenyl, 3,4-dimethylphenyl, 4-tert-butylphenyl, 4-cyclopropylphenyl, 4-diethylaminophenyl, 4-(trifluoromethyl)phenyl, 4-methoxyphenyl, 4-(difluoromethoxy)phenyl, 4-(trifluoromethoxy)phenyl, 3-chloropheny, 4-chlorophenyl, and 3,4-dichlorophenyl.
10 . A compound according to claim 2 , wherein R 5 is hydrogen and R 4 is substituted or unsubstituted heteroaryl.
11 . A compound according to claim 10 , wherein R 4 is a substituted or unsubstituted heteroaryl unit, said heteroaryl unit chosen from 1,2,3,4-tetrazol-1-yl , 1,2,3,4-tetrazol-5-yl, [1,2,3]triazol-4-yl, [1,2,3]triazol-5-yl, [1,2,4]triazol-4-yl, [1,2,4]triazol-5-yl, imidazol-2-yl, imidazol-4-yl, pyrrol-2-yl, pyrrol-3-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, [1,2,4]oxadiazol-3-yl, [1,2,4]oxadiazol-5-yl, [1,3,4]oxadiazol-2-yl, furan-2-yl, furan-3-yl, thiophene-2-yl, thiophene-3-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, [1,2,4]thiadiazol-3-yl, [1,2,4]thiadiazol-5-yl, and [1,3,4]thiadiazol-2-yl.
12 . A compound according to claim 11 , wherein R 4 is chosen from furan-2-yl, thiophene-2-yl, 5-chlorothiophene-2-yl, and 5-methylthiophene-2-yl.
13 . A compound according to claim 1 , wherein R is a unit wherein R 4 and R 5 are taken together to form a saturated or unsaturated ring having from 5 to 7 atoms.
14 . A compound according to claim 13 , wherein R is 5,6-dihydro-4H-cyclopenta[d]thiazol-2-yl or 4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl.
15 . A compound according to claim 1 , wherein R units have the formula
16 . A compound according to claim 15 , wherein R 6 is hydrogen.
17 . A compound according to claim 15 , wherein R 6 is chosen from methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, and tert-butyl.
18 . A compound according to claim 15 , wherein R 6 is substituted or unsubstituted phenyl.
19 . A compound according to claim 18 , wherein R 6 is chosen from include phenyl, 2-fluorophenyl, 2-chlorophenyl, 2-methylphenyl, 2-methoxyphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-methylphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-methylphenyl, and 4-methoxyphenyl.
20 . A compound according to claim 15 , wherein R 6 is a substituted or unsubstituted heteroaryl unit, said heteroaryl unit chosen from 1,2,3,4-tetrazol-1-yl, 1,2,3,4-tetrazol-5-yl, [1,2,3]triazol-4-yl, [1,2,3]triazol-5-yl, [1,2,4]triazol- 4 -yl, [1,2,4]triazol-5-yl, imidazol-2-yl, imidazol-4-yl, pyrrol-2-yl, pyrrol-3-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, isoxazol-3-yl, isoxazol-4-yl, isoxazol-5-yl, [1,2,4]oxadiazol-3-yl, [1,2,4]oxadiazol-5-yl, [1,3,4]oxadiazol-2-yl, furan-2-yl, furan-3-yl, thiophene-2-yl, thiophene-3-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, [1,2,4]thiadiazol-3-yl, [1,2,4]thiadiazol-5-yl, and [1,3,4]thiadiazol-2-yl.
21 . A compound according to claim 20 , wherein R 6 is chosen from thiophene-2-yl, thiophene-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, 2,5-dimethylthiazol-4-yl, 2,4-dimethylthiazol-5-yl, 4-ethylthiazol-2-yl, oxazol-2-yl, oxazol-4-yl, oxazol-5-yl, and 3-methyl-1,2,4-oxadiazol-5-yl.
22 . A compound according to claim 15 , wherein R 6 has the formula:
R 7 is C 1 -C 4 substituted or unsubstituted alkyl and substituted or unsubstituted phenyl.
23 . A compound according to claim 22 , wherein R 6 is 4-chlorobenzenesulfonylmethyl or tert-butylsulfonylmethyl.
24 . A compound according to claim 1 , wherein R 1 is hydrogen.
25 . A compound according to claim 1 , wherein R 1 is substituted or unsubstituted phenyl or benzyl.
25 . A compound according to claim 25 , wherein R 1 is benzyl.
26 . A compound according to claim 1 , wherein R 1 is C 1 -C 6 linear or branched alkyl.
27 . A compound according to claim 26 , wherein R 1 is iso-propyl.
28 . A compound according to claim 1 , wherein R 2 is a C 1 -C 6 linear or branched alkoxy unit having the formula:
—OR 8 wherein R 8 is a C 1 -C 6 linear or branched alkyl unit chosen from methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, or n-hexyl.
29 . A compound according to claim 28 , wherein R 8 is methyl, ethyl, or tert-butyl.
30 . A compound according to claim 1 , wherein R 2 is a C 1 -C 6 linear or branched alkyl unit.
31 . A compound according to claim 1 , wherein R 3 is hydrogen or methyl.
32 . A compound according to claim 31 , wherein R 3 is hydrogen.
33 . A compound having the formula:
wherein R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 4 and R 5 are each independently chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl;
iv) substituted or unsubstituted heteroaryl; or
R 4 and R 5 can be taken together to form a saturated or unsaturated ring having from 5 to 7 atoms.
34 . A compound having the formula:
wherein R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 6 is chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl; and
iv) substituted or unsubstituted heteroaryl.
35 . A compound having the formula:
wherein R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 4 and R 5 are each independently chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl;
iv) substituted or unsubstituted heteroaryl; or
R 4 and R 5 can be taken together to form a saturated or unsaturated ring having from 5 to 7 atoms.
36 . A compound having the formula:
wherein R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 6 is chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl; and
iv) substituted or unsubstituted heteroaryl.
37 . A compound having the formula:
wherein R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 4 and R 5 are each independently chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl;
iv) substituted or unsubstituted heteroaryl; or
R 4 and R 5 can be taken together to form a saturated or unsaturated ring having from 5 to 7 atoms.
38 . A compound having the formula:
wherein R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 6 is chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl; and
iv) substituted or unsubstituted heteroaryl.
39 . A compound chosen from;
4-{(S)-2-[(S)-2-(tert-Butoxycarbonyl)-3-phenylpropanamido]-2-(4-ethylthiazol-2-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-[(R)-2-(tert-Butoxycarbonyl)-3-phenylpropanamido]-2-(4-ethylthiazol-2-yl) ethyl}phenylsulfamic acid; {1-[1-(5-Ethylthiazol-2-yl)-(S)-2-(4-sulfoaminophenyl)ethylcarbamoyl]-(S)-2-phenylethyl }methyl carbamic acid tert-butyl ester; {(S)-2-Phenyl-1-[1-(2-phenylthiazol-2-yl)-(S)-2-(4-sulfoaminophenyl)ethyl-carbamoyl]ethyl}carbamic acid tert-butyl ester 4-{(S)-2-(S)-2-(tert-Butoxycarbonyl)-3-phenylpropaneamido-2-(2-phenylthiazole-4-yl)}phenylsulfamic acid; 4-{(S)-2-(4-Ethylthiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(thiazol-2-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(4-methylthiazol-2-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(4-propylthiazol-2-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-(4-tert-Butylthiazol-2-yl)-2- [(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(4-Cyclopropylthiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(4-Cyclohexylthiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenyl-propanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(4,5-Dimethylthiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenyl-propanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(4-Ethyl-5-methylthiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenyl-propanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-[4-(2,2,2-trifluoroethyl) thiazol-2-yl]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido)-2-[4-(3,3,3-trifluoropropyl) thiazol-2-yl]ethyl}phenylsulfamic acid; 4-{(S)-2-[4-(2,2-Difluorocyclopropyl)thiazol-2-yl]-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-[4-(methoxymethyl) thiazol-2-yl]ethyl}phenylsulfamic acid; 4-{(S)-2-(4-(Ethoxycarbonyl)thiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(5-phenylthiazol-2-yl)) ethyl}phenylsulfamic acid; 4-{(S)-2-(4-tert-Butylthiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(4-Ethyl-5-phenylthiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[4-(3,4-Dimethylphenyl)thiazol-2-yl]-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[4-(4-Chlorophenyl)thiazol-2-yl]-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(4-phenylthiazol-2-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-[4-(thiophen-2-yl) thiazol-2-yl]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-[4-(thiophen-3-yl) thiazol-2-yl]ethyl}phenylsulfamic acid; 4-{(S)-2-(4-Ethylthiazol-2-yl)-2-[(S)-2-(methoxycarbinyl)-3-phenylpropionamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(5,6-Dihydro-4H-cyclopenta[d]thiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(4,5,6,7-tetrahydrobenzo [d]thiazol-2-yl)ethyl}phenylsulfamic acid; 4-{(S)-2-[4-(5-Chlorothiophen-2-yl)thiazol-2-yl]-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Ethoxycarbonyl)-3-phenylpropanamido]-2-(4-ethylthiazol-2-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(2-ethylthiazol-4-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(2-methylthiazol-4-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-(2-Ethylthiazole-4-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(2-Isopropylthiazol-4-yl)-2-{(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(2-Cyclopropylthiazol-4-yl)-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-{2-[(4-Chlorophenylsulfonyl)methyl]thiazol-4-yl}-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[2-(tert-Butylsulfonylmethyl)thiazol-4-yl]-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropionamido]-2-(2-phenylthiazole-4-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-[2-(thiophen-2-yl) thiazol-4-yl]ethyl}phenylsulfamic acid; 4-{(S)-2-[2-(3-Chlorothiophen-2-yl)thiazol-4-yl]-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-[2-(3-methylthiophen-2-yl) thiazol-4-yl]ethyl}phenylsulfamic acid; 4-{[(S)-2-(2-(Furan-2-yl)thiazol-4-yl]-2-[(S)-2-(methoxycarbonyl)-3-phenylpropanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-[2-(2-methylthiazole-4-yl) thiazole-4-yl]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-(2-pyrazine-2-yl) thiazole-4-yl}phenylsulfamic acid; and 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-3-phenylpropanamido]-2-[2-(6-methylpyridin-3-yl) thiazol-4-yl]ethyl}phenylsulfamic acid.
40 . A compound chosen from:
4-[(S)-2-((S)-2-Acetamido-3-phenylpropanamido)-2-(4-ethylthiazol-2-yl) ethyl]phenylsulfamic acid; 4-[(S)-2-((S)-2-Acetamido-3-phenylpropanamido)-2-(4-tert-butylthiazol-2-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-((S)-2-Acetamido-3-phenylpropanamido)-2-[4-(thiophen-3-yl) thiazol-2-yl]ethyl)phenylsulfamic acid; 4-{(S)-2-[(S)-2-(tert-Butoxycarbonyl)-3-methylbutanamido]-2-(4-ethylthiazol-2-yl) ethyl}phenylsulfamic acid; (S)-4-{2-[2-(tert-Butoxycarbonyl)acetamide]-2-(4-ethylthiazol-2-yl)ethyl}phenylsulfamic acid; (S)-4-{2-(4-Ethylthiazol-2-yl)-2-[2-(methoxycarbonyl)acetamido]ethyl}phenylsulfamic acid; 4-{(S)-2-(4-Ethylthiazol-2-yl)-2-{(S)-2-(methoxycarbonyl)-3-methylbutanamido]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(tert-Butoxycarbonyl)-4-methylpentanamido]-2-(4-ethylthiazol-2-yl) ethyl}phenylsulfamic acid; 4-{(S)-2-(4-Ethylthiazol-2-yl)-2-[(S)-2-(methoxycarbonyl)-4-methylpentanamido]ethyl}phenylsulfamic acid; 4-((S)-2-(4-Ethylthiazol-2-yl)-2-{( 5 )-2-[2-(methoxycarbonyl)acetamide]-3-phenylpropanamido}ethyl)phenylsulfamic acid; 4-{(S)-2-[(S)-2-(tert-Butoxycarbonyl)-4-methylpentanamido]-2-[2-(thiophen-2-yl) thiazol-4-yl]ethyl}phenylsulfamic acid; 4-{(S)-2-[(S)-2-(Methoxycarbonyl)-4-methylpentanamido]-2-[2-(thiophen-2-yl) thiazol-4-yl]ethyl}phenylsulfamic acid; and (S)-4-{2-[2-(tert-Butoxycarbonyl)acetamide]-2-(4-ethylthiazol-2-yl)ethyl}-phenylsulfamic acid.
41 . A compound having the formula:
wherein R is a substituted or unsubstituted thiazolyl unit having the formula:
R 4 and R 5 are each independently chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl;
iv) substituted or unsubstituted heteroaryl; or
R 4 and R 5 can be taken together to form a saturated or unsaturated ring having from 5 to 7 atoms;
said substitutions are independently chosen from one or more C 1 -C 6 linear, branched, or cyclic alkyl, halogen, hydroxyl, or cyano units;
R 6 is a unit chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl; and
iv) substituted or unsubstituted heteroaryl;
R 1 is chosen from:
i) hydrogen;
ii) C 1 -C 6 linear or branched alkyl;
iii) substituted or unsubstituted phenyl; or
iv) substituted or unsubstituted benzyl;
R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 3 is hydrogen or C 1 -C 4 linear or branched alkyl.
42 . A compound chosen from:
[1-(S)-(Phenylthiazol-2-yl)-2-(4-sulfoaminophenyl)ethyl]-carbamic acid tert-butyl ester; (S)-4-(2-(4-Methylthiazol-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; (S)- 4 -( 2 -( 4 -Ethylthiazole- 2 -yl)- 2 -pivalamideoethyl)phenylsulfamic acid; (S)-4-(1-(4-Hydroxymethyl)thiazole-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; (S)-4-(2-(4-Ethoxycarbonyl)thiazole-2-yl)-2-pivalamideoethyl)phenylsulfamic acid; (S)-4-(2-(4-Phenylthiazole-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; 4-((S)-2-(4-(3-Methoxyphenyl)thiazol-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; N-((S)-1-(4-(4-Chlorophenyl)thiazol-2-yl)-2-(4-nitrophenyl)ethyl)pivalamide; 4-((S)-2-(4-(3-methoxyphenyl)thiazol-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; 4-((S)-2-(4-(2,4-Dimethoxyphenyl)thiazol-2-yl)-2-pivalamidoethyl) phenylsulfamic acid; (S)-4-(2-(4-benzylthiazol-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; (S)-4-(2-Pivalamido-2-(4-(thiophen-2-ylmethyl)thiazol-2-yl)ethyl)phenylsulfamic acid; (S)-4-(2-(4-(3-Methoxybenzyl)thiazol-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; 4-((S)-2-(4-(2,3-Dihydrobenzo[b][1,4]dioxin-6-yl)thiazol-2-yl)-2-pivalamidoethyl) phenylsulfamic acid; (S)-4-(2-(5-Methyl-4-phenylthiazol-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; (S)-4-(2-(4-(4-Biphenyl)thiazol-2-yl)-2-pivalamidoethyl)phenylsulfamic acid; (S)-4-(2-tert-Butoxycarbonyl-2-(2-methylthaizole-4-yl)-phenylsulfamic acid (S)-4-(2-(tert-Butoxycarbonyl)-2-(4-propylthiazol-2-yl)ethyl)-phenyl sulfamic acid; (S)-4-(2-(tert-Butoxycarbonyl)-2-(4-tert-butylthiazol-2-yl)ethyl)-phenyl sulfamic acid; (S)-4-(2-(tert-Butoxycarbonyl)-2-(4-(methoxymethyl)thiazol-2-yl)ethyl)-phenyl sulfamic acid; (S)-tert-Butyl 2-(4-nitrophenyl)-1-(4-(trifluoromethyl)thiazol-2-yl) ethylcarbamate; (S)-4-(2-tert-Butoxycarbonyl)-2-(4-(2-hydroxymethyl)thiazole-2-yl) ethyl)phenylsulfamic acid; (S)-4-(2-tert-Butoxycarbonyl)-2-(4-(2-ethoxy-2-oxoethyl)-thiazole-2-yl)-ethyl) phenylsulfamic acid; (S)-4-(2-(tert-Butoxycarbonyl)-2-(4-(2-(2-methoxy-2-oxoyethyl amino)-2-oxoethyl) thiazole-2-yl)ethyl)phenylsulfamic acid; (S)-4-(2-(tert-Butoxycarbonyl)-2-(2-pivalamidothiazole-4-yl)ethyl) phenylsulfamic acid; (S)-4-(2-(tert-Butoxycarbonyl)-2-(5-phenylthiazol-2-yl)ethyl)-phenyl sulfamic acid; 4-((S)-2-(tert-Butoxycarbonyl)-2-(4-(3-(trifluoromethyl)phenyl)thiazol-2-yl) ethyl)-phenyl sulfamic acid; (S)-4-(2-(tert-Butoxycarbonyl)-2-(5-phenylthiazol-2-yl)ethyl)-phenyl sulfamic acid; (S)-{4-[2,2-Dimethyl-propionylamino)-2-(2-phenyl-thiazole-4-yl)ethyl]phenyl}sulfamic acid; (S)-4-(2-tert-Butoxycarbonyl)-2-(4-phenyl)-2-(4-phenylthiazole-2-yl)-ethyl) phenylsulfamic acid; (S,S)-2-(2-{2-[1-tert-Butoxycarbonylamino-2-(4-sulfoamino-phenyl)-ethyl]-thiazole-4-yl}-acetylamino-3-phenyl-propionic acid methyl ester; (S)-[1-{1-Oxo-4-[2-(1-phenyl-1H-tetrazole-5-sulfonylethyl]-1H-1λ 4 -thiazole-2-yl}-2-(4-sulfamino-phenyl)-ethyl]-carbamic acid tert-butyl ester; 4-((S)-2-(tert-Butoxycarbonyl)-2-(4-(thiophen-3-yl)thiazol-2-yl)ethyl)phenyl sulfamic acid; (S)-4-(2-(Benzo[d]thiazol-2-yl)-2-(tert-butoxycarbonyl)ethyl)phenylsulfamic acid; and (S)-4-(2-tert-Butoxycarbonyl-2-(2-methylthaizole-4-yl)-phenylsulfamic acid.
43 . A pharmaceutical composition comprising:
A) one or more compounds according to claim 1 ; and B) one or more excipients or carriers.
44 . A method for treating a disease chosen from a disorder chosen from diabetic retinopathy, macular degeneration, cancer, sickle cell anemia, sarcoid, syphilis, pseudoxanthoma elasticum, Paget's disease, vein occlusion, artery occlusion, carotid obstructive disease, chronic uveitis/vitritis, mycobacterial infections, Lyme's disease, systemic lupus erythematosis, retinopathy of prematurity, Eales' disease, Behcet's disease, infections causing a retinitis or choroiditis, presumed ocular histoplasmosis, Best's disease, myopia, optic pits, Stargardt's disease, pars planitis, chronic retinal detachment, hyperviscosity syndrome, toxoplasmosis, trauma and post-laser complications, diseases associated with rubeosis, and proliferative vitreoretinopathy comprising administering to a human a compound according to claim 1 .
45 . A method for treating a disease chosen from a disorder chosen from Crohn's disease and ulcerative colitis, psoriasis, sarcoidosis, rheumatoid arthritis, hemangiomas, Osler-Weber-Rendu disease, or hereditary hemorrhagic telangiectasia, solid or blood borne tumors and acquired immune deficiency syndrome comprising administering to a human a compound according to claim 1 .
46 . A method for treating a disease chosen from a disorder chosen from skeletal muscle and myocardial ischemia, stroke, coronary artery disease, peripheral vascular disease, coronary artery disease comprising administering to a human a compound according to claim 1 .
47 . A method for regulating angiogenesis in a human comprising administering to a human a compound according to claim 1 .
48 . A method for vascularizing ischemic tissue in a human comprising administering to a human a compound according to claim 1 .
49 . A method for promoting the growth of skin graft replacements comprising administering to a human a compound according to claim 1 .
50 . A method for promoting tissue repair in the context of guided tissue regeneration (GTR) procedures comprising administering to a human a compound according to claim 1 .
51 . A compound having the formula:
wherein R is a substituted or unsubstituted thiazolyl unit having the formula:
R 2 is chosen from:
i) C 1 -C 6 linear or branched alkyl; or
ii) C 1 -C 6 linear or branched alkoxy;
R 4 and R 5 are each independently chosen from:
i) hydrogen;
ii) substituted or unsubstituted C 1 -C 6 linear, branched, or cyclic alkyl;
iii) substituted or unsubstituted phenyl;
iv) substituted or unsubstituted heteroaryl; or
R 4 and R 5 can be taken together to form a saturated or unsaturated ring having from 5 to 7 atoms.
52 . A pharmaceutical composition comprising:
A) one or more compounds according to any of claims 33 - 38 and 51 ; and B) one or more excipients or carriers.
53 . A method for treating a disease chosen from a disorder chosen from diabetic retinopathy, macular degeneration, cancer, sickle cell anemia, sarcoid, syphilis, pseudoxanthoma elasticum, Paget's disease, vein occlusion, artery occlusion, carotid obstructive disease, chronic uveitis/vitritis, mycobacterial infections, Lyme's disease, systemic lupus erythematosis, retinopathy of prematurity, Eales' disease, Behcet's disease, infections causing a retinitis or choroiditis, presumed ocular histoplasmosis, Best's disease, myopia, optic pits, Stargardt's disease, pars planitis, chronic retinal detachment, hyperviscosity syndrome, toxoplasmosis, trauma and post-laser complications, diseases associated with rubeosis, and proliferative vitreoretinopathy comprising administering to a human a compound according to any of claims 33 - 38 and 51 .
54 . A method for treating a disease chosen from a disorder chosen from Crohn's disease and ulcerative colitis, psoriasis, sarcoidosis, rheumatoid arthritis, hemangiomas, Osler-Weber-Rendu disease, or hereditary hemorrhagic telangiectasia, solid or blood borne tumors and acquired immune deficiency syndrome comprising administering to a human a compound according to any of claims 33 - 38 and 51 .
55 . A method for treating a disease chosen from a disorder chosen from skeletal muscle and myocardial ischemia, stroke, coronary artery disease, peripheral vascular disease, coronary artery disease comprising administering to a human a compound according to any of claims 33 - 38 and 51 .
56 . A method for regulating angiogenesis in a human comprising administering to a human a compound according to any of claims 33 - 38 and 51 .
57 . A method for vascularizing ischemic tissue in a human comprising administering to a human a compound according to any of claims 33 - 38 and 51 .
58 . A method for promoting the growth of skin graft replacements comprising administering to a human a compound according to any of claims 33 - 38 and 51 .
59 . A method for promoting tissue repair in the context of guided tissue regeneration (GTR) procedures comprising administering to a human a compound according to any of claims 33 - 38 and 51 .
60 . A compound according to any of claims 1 , 33 - 38 and 51 , wherein the compound is a pharmaceutically acceptable of either basic groups or acid groups.
61 . A compound according to claim 60 , wherein the compounds are salts comprising anions chosen from chloride, bromide, iodide, sulfate, bisulfate, carbonate, bicarbonate, phosphate, formate, acetate, propionate, butyrate, pyruvate, lactate, oxalate, malonate, maleate, succinate, tartrate, fumarate, and citrate.
62 . A compound according to claim 60 , wherein the compounds are salts comprising cations chosen from sodium, lithium, potassium, calcium, magnesium, and bismuth.Cited by (0)
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