Human protein tyrosine phosphatase inhibitors and methods of use

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.

1 - 63 . (canceled) 
     
     
         64 . A pharmaceutical composition comprising:
 a) a therapeutically-effective amount of a HPTP-β inhibitor; and   b) a pharmaceutically-acceptable excipient,   
       wherein the therapeutically-effective amount of the HPTP-β inhibitor is about 0.01 mg to about 100 mg. 
     
     
         65 . The composition of  claim 64 , wherein the HPTP-β inhibitor is a phenylsulfamic acid. 
     
     
         66 . The composition of  claim 64 , wherein the HPTP-β inhibitor is a sodium salt. 
     
     
         67 . The composition of  claim 64 , wherein the pharmaceutically-acceptable excipient is a pH stabilizer. 
     
     
         68 . The composition of  claim 64 , wherein the pharmaceutically-acceptable excipient improves cellular potency of the HPTP-β inhibitor. 
     
     
         69 . The composition of  claim 64 , wherein the pharmaceutically-acceptable excipient improves pharmacokinetic properties of the HPTP-β inhibitor. 
     
     
         70 . The composition of  claim 64 , wherein the pharmaceutically-acceptable excipient increases oral bioavailability of the HPTP-β inhibitor. 
     
     
         71 . A method of vascularizing ischemic tissue in a subject in need thereof, the method comprising administering to a subject in need thereof:
 a) a therapeutically-effective amount of a Tie-2 modulator; and   b) a pharmaceutically-acceptable excipient,   
       wherein the therapeutically-effective amount of the Tie-2 modulator is about 0.01 mg to about 100 mg. 
     
     
         72 . The method of  claim 71 , wherein the Tie-2 modulator is an HPTP-β inhibitor. 
     
     
         73 . The method of  claim 71 , wherein the pharmaceutically-acceptable excipient is a pH stabilizer. 
     
     
         74 . The method of  claim 71 , wherein the pharmaceutically-acceptable excipient improves cellular potency of the Tie-2 modulator in the subject. 
     
     
         75 . The method of  claim 71 , wherein the pharmaceutically-acceptable excipient improves pharmacokinetic properties of the Tie-2 modulator in the subject. 
     
     
         76 . The method of  claim 71 , wherein the pharmaceutically-acceptable excipient improves oral bioavailability of the Tie-2 modulator in the subject. 
     
     
         77 . The method of  claim 71 , wherein the ischemic tissue is in an eye of the subject. 
     
     
         78 . The method of  claim 71 , wherein the administering is subcutaneous. 
     
     
         79 . The method of  claim 71 , wherein the administering is daily. 
     
     
         80 . The method of  claim 71 , wherein the subject is human. 
     
     
         81 . The method of  claim 71 , further comprising measuring vascularization of the ischemic tissue in the subject. 
     
     
         82 . The method of  claim 81 , wherein the measuring of vascularization is by single photon emission computed tomography (SPECT), positron emission tomography (PET), magnetic resonance imaging (MRI), angiography, histologic evaluation, or a combination thereof. 
     
     
         83 . A method of preparing a composition, the method comprising mixing {1-[2-(S)-(4-(S)-aminophenyl)-1-(2-ethylthiazol-4-yl)ethyl-carbamoyl]-2-phenylethyl}-carbamic acid methyl ester, acetonitrile, and sulfur trioxide pyridine.