Salts Of Methyl 2-((R)-(3-Chlorophenyl)((R)-1-((S)-2-(Methylamino)-3-((R)-Tetrahydro-2H-Pyran-3-Yl)Propylcarbamoyl)Piperidin-3-Yl)Methoxy)Ethylcarbamate

Abstract

Mucic acid salts of a compound represented by the following structural formula: are disclosed. In particular, single crystalline mucic acid salts of the compound represented by structural formula (I) are characterized by a variety of properties and physical measurements. Methods of producing the mucic acid salts, using the salts to antagonize one or more aspartic proteases, and methods of treating a number of aspartic protease mediated disorders using the salts are described herein.

1 .- 45 . (canceled) 
     
     
         46 . A method for treating an aspartic protease mediated disorder in a subject comprising administering to the subject an effective amount of a crystalline form of mucic acid salt of a compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
       wherein the crystalline form is selected from Form B as characterized by an x-ray diffraction pattern in accordance with  FIG. 1  or  FIG. 2 , Form D as characterized by an x-ray diffraction pattern in accordance with  FIG. 4 , or a combination thereof; and wherein the disorder is hypertension, nephropathy, glomerulonephritis, proteinuria, albuminuria, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, cardiomyopathy post-infarction, vasculopathy, or hyperaldosteronism. 
     
     
         47 . (canceled) 
     
     
         48 . The method of  claim 46 , further comprising administering one or more additional agents selected from the group consisting of an α-blockers, β-blocker, a calcium channel blocker, a diuretic, an angiotensin converting enzyme inhibitor, a dual angiotensin converting enzyme and neutral endopeptidase inhibitor, an angiotensin-receptor blocker, dual angiotensin-receptor blocker and endothelin receptor antagonist, a aldosterone synthase inhibitor, a aldosterone-receptor antagonist, and an endothelin receptor antagonist. 
     
     
         49 . The method of  claim 46 , wherein the salt is a hemi mucate salt. 
     
     
         50 . The method of  claim 49 , wherein at least 50% by weight of the crystalline form is in a single crystalline form. 
     
     
         51 . The method of  claim 49 , wherein at least 90% by weight of the crystalline form is a single crystalline form. 
     
     
         52 . The method of  claim 50  or  51 , wherein the single crystalline form is Form B. 
     
     
         53 . The method of  claim 50  or  51 , wherein the single crystalline form is Form D. 
     
     
         54 . The method of  claim 50  or  51 , wherein the single crystalline form is characterized by at least three major x-ray powder diffraction peaks at 2θ angles selected from 7.61°, 16.38°, 17.08°, 19.16° and 20.12°. 
     
     
         55 . The method of  claim 50  or  51 , wherein the single crystalline form is characterized by the following major x-ray powder diffraction peaks at 2θ angles 7.61°, 16.38°, 17.08°, 19.16° and 20.12°. 
     
     
         56 . The method of  claim 50  or  51 , wherein the single crystalline form is characterized by x-ray powder diffraction peaks at 2θ angles of 3.79°, 5.15°, 6.76°, 7.61°, 8.83°, 10.32°, 11.41°, 11.94°, 12.47°, 13.58°, 15.22°, 16.38°, 17.08°, 19.16° and 20.12°. 
     
     
         57 . The method of  claim 50  or  51 , wherein the single crystalline form is characterized by at least four major x-ray powder diffraction peaks at 2θ angles selected from 6.57°, 7.65°, 12.27°, 14.75°, 16.96°, 17.42°, 19.25°, 19.98°, and 20.77°. 
     
     
         58 . The method of  claim 50  or  51 , wherein the single crystalline form is characterized by at least seven major x-ray powder diffraction peaks at 2θ angles selected from 6.57°, 7.65°, 12.27°, 14.75°, 16.96°, 17.42°, 19.25°, 19.98°, and 20.77°. 
     
     
         59 . The method of  claim 50  or  51 , wherein the single crystalline form is characterized by the following major x-ray powder diffraction peaks at 2θ angles 6.57°, 7.65°, 12.27°, 14.75°, 16.96°, 17.42°, 19.25°, 19.98°, and 20.77°. 
     
     
         60 . The method of  claim 50  or  51 , wherein the single crystalline form is characterized by x-ray powder diffraction peaks at 2θ angles of angles selected from angles selected from 2.96°, 4.27°, 5.17°, 5.90°, 6.57°, 7.25°, 7.65°, 8.95°, 9.78°, 10.52°, 11.50°, 12.27°, 12.97°, 13.38°, 14.05°, 14.75°, 15.50°, 16.32°, 16.96°, 17.42°, 18.39°, 19.25°, 19.98°, 20.77°, 22.22°, 22.91°, 23.89°, 24.58°, 26.70°, and 28.51°. 
     
     
         61 . The method of  claim 46 , wherein the aspartic protease is renin 
     
     
         62 . A method of antagonizing renin in a subject in need thereof, comprising administering to the subject an effective amount of a crystalline form of mucic acid salt of a compound represented by the following structural formula: 
       
         
           
           
               
               
           
         
       
       wherein the crystalline form is selected from Form B as characterized by an x-ray diffraction pattern in accordance with  FIG. 1  or  FIG. 2 , Form D as characterized by an x-ray diffraction pattern in accordance with  FIG. 4 , or a combination thereof.