NRF2 Regulators

Abstract

The present invention relates to bis aryl analogs, pharmaceutical compositions containing them and their use as Nrf2 regulators.

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
       
       wherein:
 A is —C(O)OR 1  or tetrazolyl; 
 R 1  is hydrogen, —CH 2 C(O)N(R 7 ) 2 , —CH 2 -(4-methyl-1,3-dioxol-2-one), —C 2-3  alkyl-OH, C 1-3  alkyl, —C 2-5  alkyl-N(R 7 ) 2 , —(CH 2 ) n -morpholinyl, —(CH 2 ) n -furyl, —CH 2 —O—C(O)—C 1-5  alkyl, —(CH 2 ) n -imidazolyl, —(CH 2 ) n -pyrrolidinyl, —(CH 2 ) n -piperidyl, or 2-oxotetrahydrofuran-3-yl; wherein the morpholinyl and piperidyl is optionally substituted by one or two C 1-3  alkyl; and the pyrrolidinyl, imidazolyl, and furyl is optionally substituted by one or two groups independently selected from C 1-3  alkyl, halo, and —O—C 1-3  alkyl; 
 R 2  is 
 —(CH 2 ) n -phenyl, which is optionally substituted by one, two, or three groups independently selected from —CN, —F, —Cl, —C(O)N(R 7 ) 2 , —C(O)OH, —C(O)CH 3 , —O—C 1-3  alkyl, —S—C 1-3  alkyl, C 1-3  alkyl, —C 1-3  alkyl-N(R 7 ) 2 , —CF 3 , and —OCF 3 ; 
 benzotriazolyl, which is optionally substituted by one, two, or three groups independently selected from —O—C 1-3  alkyl, —F, —Cl, —CF 3 , —OCF 3 , C 1-3  alkyl, and —C 2-3  alkyl-NH—C(O)—O—C 1-4  alkyl, or is optionally substituted by R 13  and optionally by one or two additional groups independently selected from —O—C 1-3  alkyl, —F, —Cl, —CF 3 , —OCF 3 , and C-13 alkyl; 
 —(CH 2 ) n -triazolyl, which is optionally substituted by one or two groups independently selected from C 1-3  alkyl and —CH 2 -phenyl; 
 —C 3-6  cycloalkyl-triazolyl, which is optionally substituted by one or two groups independently selected from C 1-3  alkyl and —CH 2 -phenyl; 
 —(CH 2 ) n -imidazolyl, which is optionally substituted by one or two groups independently selected from C 1-3  alkyl and —CH 2 -phenyl; 
 —(CH 2 ) n -pyrazolyl, which is optionally substituted by one or two groups independently selected from C 1-3  alkyl and —CH 2 -phenyl; 
 dihydroindenyl, which is optionally substituted by one, two, or three groups independently selected from C 1-3  alkyl, —F, —OCH 3 , and ═O; 
 isoindolinyl, which is optionally substituted by one, two, or three groups independently selected from C 1-3  alkyl, —F, —OCH 3 , and ═O; 
 —(CH 2 ) n -pyridyl, which is optionally substituted by one, two, or three groups independently selected from C 1-3  alkyl, —F, —OCH 3 , and ═O; 
 triazolopyridyl, which is optionally substituted by one or two groups independently selected from —O—C 4-3  alkyl, —F, and C 1-3  alkyl; 
 tetrazolopyridyl, which is optionally substituted by —O—C 1-3  alkyl, —F, or C 1-3  alkyl; 
 1,2,3,4-tetrahydroisoquinolinyl, which is optionally substituted by one or two groups independently selected from —O—C 1-3  alkyl, —F, —Cl, —CF 3 , —OCF 3 , and C 1-3  alkyl; 
 C 1-6  alkyl, —(CH 2 ) n —C 3-6  cycloalkyl, —C 1-3  alkyl-O—C 1-3  alkyl, or —C 1-3  alkyl-C(O)N(R 14 ) 2 ; 
 R 3  is R 4 —SO 2 —N(R 6 )—; 
 R 4  is phenyl, C 5-6  cycloalkyl, thienyl, imidazolyl, pyrazolyl, pyridyl, piperidyl, tetrahydro-2H-pyranyl, C 1-3  alkyl, or 
 
       
         
           
           
               
               
           
         
       
       wherein each of R 4  is optionally substituted by one or two groups independently selected from C 1-3  alkyl, —NH—C(O)—CH 3 , —O—C 1-3 alkyl, —C(O)—CH 3 , ═O, and OH;
 or R 3  is 
 
       
         
           
           
               
               
           
         
         X is CH 2 , NR 9  or O; 
         each Y is independently N or CH; provided that not more than one Y is N; 
         each Z is independently O, CH 2 , or NR 10 ; 
         R 5  is hydrogen, —F, —Cl, C 1-3  alkyl, or —CF 3 ; 
         R 6  is hydrogen, C 1-3  alkyl, or —C 2-3  alkyl-OH; 
         each R 7  is independently hydrogen or C 1-3  alkyl; 
         each R 8  is independently hydrogen, —NH 2 , or C 1-3  alkyl, provided that at least one R 8  is hydrogen or C 1-3  alkyl; 
         each R 9  is independently hydrogen or C 1-3  alkyl; 
         or R 9  and R 13  taken together represent —CH 2 —CH═CH—(CH 2 ) 2 — or —(CH 2 ) 5 —; 
         R 10  is —C(O)—CH 3 ; 
         R 11  is hydrogen, halo, —CF 3 , —CN, —C(O)N(R 7 ) 2 , —C 1-3  alkyl-N(R 7 ) 2 , or —C 1-3  alkyl-NH—C(O)—O—C 1-4  alkyl; 
         R 12  is hydrogen; 
         or R 5  and R 12  taken together represent —CH 2 CH 2 —; 
         each R 14  is independently hydrogen, C 1-3  alkyl, or —CH 2 -phenyl; 
         each n is independently 0, 1, 2, or 3; and 
         m is 1 or 2; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound or pharmaceutically acceptable salt according to  claim 1  wherein A is —C(O)OR 1  and R 1  is hydrogen, —C 1-5  alkyl-N(R 7 ) 2 , —(CH 2 ) n -morpholinyl, —(CH 2 ) n -imidazoyl, —(CH 2 ) n -pyrrolidinyl, or —(CH 2 ) n -piperidyl. 
     
     
         3 . The compound or pharmaceutically acceptable salt according to  claim 1  wherein A is —C(O)OH. 
     
     
         4 . The compound or pharmaceutically acceptable salt according to  claim 1  wherein R 2  is:
 phenyl substituted by one, two, or three groups independently selected from —CN, —F, —Cl, C 1-3  alkyl, and —O—C 1-3  alkyl; 
 benzotriazolyl substituted by one, two, or three groups independently selected from —O—C 1-3  alkyl and C 1-3  alkyl; or 
 —(CH 2 ) 2 -triazolyl substituted by one or two groups independently selected from C 1-3  alkyl or —CH 2 -phenyl. 
 
     
     
         5 . The compound or pharmaceutically acceptable salt according to  claim 1  wherein R 2  is benzotriazolyl substituted by one or two groups independently selected from —O—C 1-3  alkyl and C 1-3  alkyl. 
     
     
         6 . The compound or pharmaceutically acceptable salt according to  claim 1  wherein R 3  is 
       
         
           
           
               
               
           
         
       
       wherein X is CH 2 , N(CH 3 ), or O and each Y is independently N or CH, provided that not more than one Y is N. 
     
     
         7 . The compound or pharmaceutically acceptable salt according to  claim 1  wherein R 5  is hydrogen, —Cl, C 1-3  alkyl, or —CF 3 . 
     
     
         8 . The compound or pharmaceutically acceptable salt according to  claim 1  wherein each R 8  is hydrogen. 
     
     
         9 . The compound according to  claim 1  represented by formula (Ib): 
       
         
           
           
               
               
           
         
       
       wherein:
 W is N or CR 2c ; 
 X is CH 2 , NR 9  or O; 
 each Y is independently N or CH; provided that not more than one Y is N; 
 R 2a  is methyl or ethyl; 
 R 2b  is hydrogen, —F, methyl, or —CF 3 ; 
 R 2c  is hydrogen or methoxy; 
 R 5  is hydrogen, —F, —Cl, methyl, ethyl, or —CF 3 ; 
 each R 9  is independently hydrogen, methyl, or ethyl; and 
 R 11  is hydrogen, halo, —CF 3 , —CN, —C(O)NH 2 , —C 1-3  alkyl-NH 2 , —C 1-3  alkyl-N(C 1-3  alkyl) 2 , or —C 1-3  alkyl-NH—C(O)—O—C 1-4  alkyl; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         10 . The compound according to  claim 1  selected from the group consisting of:
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((3-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-((1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((N-(2-hydroxyethyl)-2-methoxypyridine-3-sulfonamido)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((N-(2-hydroxyethyl)-2-methoxypyridine-3-sulfonamido)methy)-4-methylphenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-((5-ethyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((5-ethyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 (S)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 (R)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((5-ethyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2,5]thiadiazepin-2(3H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(3-((5-ethyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2,5]thiadiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-((5-ethyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((5-ethyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2,5]thiadiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 (3R)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 (3S)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methy-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methy-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((5-ethyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2,5]thiadiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(4-ethyl-3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(3-methoxyphenyl)propanoic acid; 
 3-(4-chloro-3-((N,4-dimethylphenylsulfonamido)methyl)phenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(4-chloro-3-((N,3-dimethylphenylsulfonamido)methyl)phenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(4-chloro-3-((N-methyl-2,3-dihydro-1H-indene-5-sulfonamido)methyl)phenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((3-acetamido-N-methylphenylsulfonamido)methyl)-4-chlorophenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(4-chloro-3-((N-methylcyclohexanesulfonamido)methyl)phenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(4-chloro-3-((N-methyl-2,3-dihydrobenzo[b][1,4]dioxine-6-sulfonamido)methyl)phenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 (3R)-3-{4-chloro-3-[(N-methylbenzenesulfonamido)methyl]phenyl}-3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)propanoic acid; 
 (3S)-3-{4-chloro-3-[(N-methylbenzenesulfonamido)methyl]phenyl}-3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)propanoic acid; 
 (3R)-3-(1,4-dimethyl-1H-1,2,3-benzotriazol-5-yl)-3-{4-methyl-3-[(N-methylbenzenesulfonamido)methyl]phenyl}propanoic acid; 
 (3S)-3-(1,4-dimethyl-1H-1,2,3-benzotriazol-5-yl)-3-{4-methyl-3-[(N-methylbenzenesulfonamido)methyl]phenyl}propanoic acid; 
 3-(3-((1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(tetrazolo[1,5-a]pyridin-7-yl)propanoic acid; 
 3-(3-(4,4-dioxido-1,4,5-oxathiazepan-5-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-fluorophenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-fluoro-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-fluorophenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-fluoro-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((1,1-dioxido-3,4-dihydro-2H-pyrido[4,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 Ethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 3-(4-chloro-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(4-chloro-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-methoxyphenyl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-chloro-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-methoxy-2-methylphenyl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(3-methyl-3H-[1,2,3]triazolo[4,5-b]pyridin-6-yl)propanoic acid; 
 3-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-6-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3,5-dimethoxyphenyl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(5-methoxypyridin-3-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-methoxy-5-(trifluoromethoxy)phenyl)-3-(4-methyl-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)propanoic acid; 
 3-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-chloro-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)propanoic acid; 
 3-(1-methyl-2-oxo-1,2-dihydropyridin-4-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(4-fluoro-1,7-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-fluoro-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((N-methylcyclopentanesulfonamido)methyl)phenyl)propanoic acid; 
 2-(Dimethylamino)-2-oxoethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 2-Hydroxyethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 Ethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 2-(Dimethylamino)ethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 2-Morpholinoethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 3-(Dimethylamino)propyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 2-Oxotetrahydrofuran-3-yl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 ((3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoyl)oxy)methyl pivalate; 
 2-(1H-Imidazol-1-yl)ethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 3-(Diethylamino)propyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 4-(Dimethylamino)butyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 3-(Dimethylamino)-2,2-dimethylpropyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 3-(Pyrrolidin-1-yl)propyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 1-(Dimethylamino)propan-2-yl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 3-morpholinopropyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 2-(5-(1-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-hydroxypropyl)-2-methylbenzyl)-5-methyl-2,3,4,5-tetrahydrobenzo[f][1,2,5]thiadiazepine 1,1-dioxide; 
 Methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 Methylpyrrolidin-3-yl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 1-Methylpiperidin-3-yl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 ((S)-1-Methylpyrrolidin-2-yl)methyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 Pyrrolidin-3-ylmethyl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 1-Methylpiperidin-4-yl 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoate; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(3-methyl-[1,2,3]triazolo[1,5-a]pyridin-6-yl)propanoic acid; 
 Ethyl 3-(3-((N-isopropylphenylsulfonamido)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoate; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-(trifluoromethyl)phenyl)propanoic acid; 
 3-(4-Chloro-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 2-Methyl-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((N-methylphenylsulfonamido)methyl)phenyl)propanoic acid; 
 2-methyl-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((N-methylphenylsulfonamido)methyl)phenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-5-(1H-1,2,3-triazol-4-yl)pentanoic acid; 
 5-(1-Benzyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 5-(2-Methyl-2H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 5-(1-Methyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 3-(7-Methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[4,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[4,3-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(1-methyl-4-(trifluoromethyl)-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-(trifluoromethyl)phenyl)propanoic acid; 
 3-(7-Methoxy-1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1-Ethyl-2-oxo-1,2-dihydropyridin-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(2-oxo-1-propyl-1,2-dihydropyridin-4-yl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(1-methyl-6-oxo-1,6-dihydropyridin-2-yl)propanoic acid; 
 3-{4-chloro-3-[(N-methylmethanesulfonamido)methyl]phenyl}-3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)propanoic acid; 
 Methyl 3-{4-chloro-3-[(N-propylpyridine-3-sulfonamido)methyl]phenyl}-3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)propanoate; 
 3-{4-chloro-3-[(N-propylpyridine-3-sulfonamido)methyl]phenyl}-3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)propanoic acid; 
 3-{4-chloro-3-[(N-ethylpyridine-3-sulfonamido)methyl]phenyl}-3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)propanoic acid; 
 3-{4-chloro-3-[(N-methylpyridine-3-sulfonamido)methyl]phenyl}-3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)propanoic acid; 
 3-{4-chloro-3-[(N-methyl-1,5-dimethyl-1H-pyrazole-4-sulfonamido)methyl]phenyl}-3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)propanoic acid; 
 3-(4-chloro-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(1-methyl-1H-1,2,3-benzotriazol-5-yl)-3-{4-methyl-3-[(N-methylbenzenesulfonamido)methyl]phenyl}propanoic acid; 
 3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((5-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; and 
 3-(7-methoxy-1-methyl-1H-1,2,3-benzotriazol-5-yl)-3-{4-methyl-3-[(N-methylbenzenesulfonamido)methyl]phenyl}propanoic acid; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         11 . The compound according to  claim 1  selected from the group consisting of:
 (S)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 (R)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 (3R)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; and 
 (3S)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid. 
 
     
     
         12 . The compound according to  claim 1  selected from the group consisting of:
 3-(1-Ethyl-4-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-(trifluoromethyl)phenyl)propanoic acid; 
 (4R)-2-(5(1-(1-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2-(1H-tetrazol-5-yl)ethyl)-2-methylbenzyl)-4-methyl-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepine 1,1-dioxide; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[3,2-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[3,2-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-((4-methyl-1,1-dioxido-4,5-dihydropyrido[2,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)pentanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-((4-methyl-1,1-dioxido-4,5-dihydropyrido[4,3-f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)pentanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[3,4-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-pyrido[3,4-b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(7-Methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[e][1,2]thiazin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-((4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[e][1,2]thiazin-2-yl)methyl)-4-methylphenyl)-3-(7-methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 6-(Benzyl(methyl)amino)-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-6-oxohexanoic acid; 
 3-(3-((7-(3-(Dimethylamino)propyl)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(4-fluoro-2-methylphenyl)propanoic acid; 
 3-(4-Methyl-3-(((S)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-6-(methylamino)-6-oxohexanoic acid; 
 3-(2-((Dimethylamino)methyl)-4-fluoro-6-methylphenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(5-Methoxy-2-methylpyridin-3-yl)-3-(4-methyl-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-5-(o-toly)pentanoic acid; 
 3-(1-Ethyl-1H-imidazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 5-(1-Ethyl-1H-pyrazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 6-Methoxy-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)hexanoic acid; 
 3-(3-((7-(3-((tert-Butoxycarbonyl)amino)propyl)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(2-methyl-1,2,3,4-tetrahydroisoquinolin-6-yl)propanoic acid; 
 5-(1-Ethyl-1H-imidazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-5-(pyridin-3-yl)pentanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-5-(o-toly)pentanoic acid; 
 3(5-(2-(Dimethylamino)ethyl)-4-fluoro-2-methylphenyl)-3-(4-methy-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(2-methylisoindolin-5-yl)propanoic acid; 
 3-5(3-Dimethylamino)propyl)-4-fluoro-2-methylphenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 6-Methyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)heptanoic acid; 
 3-(3-(((R)-8-Chloro-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-(((R)-8-Cyano-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-(((R)-8-carbamoyl-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(5-((Dimethylamino)methyl)-4-fluoro-2-methylphenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(5-(2-(Dimethylamino)ethyl)-4-fluoro-2-methylphenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 2-Amino-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((3,3-dioxido-4,5-dihydrobenzo[d][1,2]thiazepin-2(1H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((2,2-dioxidohexahydro-1H-benzo[d][1,2]thiazin-3(4H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((2,2-dioxido-1H-benzo[d][1,2]thiazin-3(4H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((3,3-dioxidooctahydrobenzo[d][1,2]thiazepin-2(1H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-5-(p-toly)pentanoic acid; 
 3-(2,4-Difluorophenyl)-3-(3-((7-(3-(dimethylamino)propyl)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)propanoic acid; 
 3-(2-(1-Methyl-1H-1,2,3-triazol-4-yl)cyclopropyl)-3-(4-methyl-3-(((R)-4-methyl-1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-2-methy-3-(4-methyl-3-((5-methyl-1-dioxido-4,5-dihydrobenzo[f][1,2,5]thiadiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)-2-methylpentanoic acid; 
 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)-2-methylpentanoic acid; 
 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 5-Methoxy-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 5-Cyclopentyl-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[4,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-(trifluoromethyl)phenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(3-((4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-(trifluoromethyl)phenyl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[4,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-(trifluoromethyl)phenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-5-(1-propyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-propyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 5-(1-Isopropyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-isopropyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[4,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-propyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[4,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-isopropyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)hexanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-((I 1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-((4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-9-fluoro-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 (S)-3-(7-Methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 (S)-3-(7-Methoxy-1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(4-Cyano-2-methylphenyl-3-(4-methyl-3-((4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(4-Cyano-2-methylphenyl)-3-(3-((7-fluoro-4-methy-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(4-Cyano-2-methylphenyl)-3-(3-((7-methoxy-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(4-Cyano-2-methylphenyl)-3-(4-methyl-3-((4-methyl-1,1-dioxido-7-(trifluoromethyl)-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(4-Cyano-2-methylphenyl-3-(4-methyl-3-((4-methyl-1,1-dioxido-7-(trifluoromethoxy)-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)propanoic acid; 
 3-(4-Cyano-2-methoxyphenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(4-Cyano-3-methoxyphenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(4-Cyano-2-fluorophenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((S)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 3-(3-((1,1-Dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 3-(3-(((R)-4-Ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-5-(1-ethyl-1H-1,2,3-triazol-4-yl)pentanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)phenyl)pentanoic acid; 
 5-(1-Ethyl-1H-1,2,3-triazol-4-yl)-3-(3-((8-fluoro-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)pentanoic acid; 
 3-(3-((7-(3-Aminopropyl)-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)methyl)-4-methylphenyl)-3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(4-Cyano-2-methylphenyl-3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(4-Cyano-2-methylphenyl)-3-(3-((4-ethyl-1,1-dioxido-3,4-dihydro-2H-pyrido[2,3-b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(4-Cyano-2-methylphenyl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3,4-Difluorophenyl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(3,4,5-trifluorophenyl)propanoic acid; 
 3-(3-Fluorophenyl)-3-(4-methyl-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-phenylpropanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(o-tolyl)propanoic acid; 
 3-(4-Fluorophenyl)-3-(4-methyl-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Fluoro-2-methylphenyl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Chloro-2-methylphenyl)-3-(4-methy-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Chlorophenyl-3-(4-methy-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Carbamoyl-2-methylphenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(4-Acetylphenyl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 4-(2-Carboxy-1-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)ethyl)-2-(ethylcarbamoyl)benzoic acid; 
 5-(2-carboxy-1-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)ethyl)-2-(ethylcarbamoyl)benzoic acid; 
 3-(1-(2-((Tert-butoxycarbonyl)amino)ethyl)-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(3-oxo-2,3-dihydro-1H-inden-5-yl)propanoic acid; 
 3-(1-(3-((Tert-butoxycarbonyl)amino)propyl)-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(4-(methylthio)phenyl)propanoic acid; 
 3-(4-Methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)-3-(1-oxo-2,3-dihydro-1H-inden-5-yl)propanoic acid; 
 3-(2,4-Difluorophenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(2,4-Difluorophenyl)-3-(4-methyl-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 Methyl 3-(1-methyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(4-methyl-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoate; 
 3-(4-Acetyl-2-methylphenyl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(4-Acetyl-2-methylphenyl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)propanoic acid; 
 3-(2-Methyl-1-oxoisoindolin-5-yl)-3-(4-methyl-3-(((R)-4-methy-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(2,2-Dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(2-Ethyl-1,3-dioxoisoindolin-5-yl)-3-(4-methyl-3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)phenyl)propanoic acid; 
 3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-3-(2-ethyl-1,3-dioxoisoindolin-5-yl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-methyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)-2,3-dihydro-1H-inden-5-yl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)-2,3-dihydro-1H-inden-5-yl)propanoic acid; 
 3-(1,4-Dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)-2,3-dihydro-1H-inden-5-yl)propanoic acid; 
 3-(3-(8-Bromo-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)-2,3-dihydro-1H-inden-5-yl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 3-(3-(8-Bromo-4-methyl-1,1-dioxido-4,5-dihydrobenzo[f][1,2]thiazepin-2(3H)-yl)-2,3-dihydro-1H-inden-5-yl)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)propanoic acid; 
 2-{34-Methyl-3,3-dioxo-10-oxa-3λ 6 -thia-2,17,18,19-tetraazaheptacyclo[24.5.2.1 2,11 .1 20,24 .0 4,9 .0 17,21 .0 29,32 ]pentatriaconta-4(9),5,7,18,20(34),21,23,26(33),27,29(32)-decaen-25-yl}acetic acid; 
 2-{4,32-Dimethyl-30,30-dioxo-23-oxa-30λ 6 -thia-1,14,15,16-tetraazahexacyclo[20.8.1.1 3,7 .1 9,13 .0 12,16 .0 24,29 ]tritriaconta-3,5,7(33),9,11,13(32),14,24(29),25,27-decaen-8-yl}acetic acid; 
 2-{4,32-Dimethyl-30,30-dioxo-23-oxa-30λ 6 -thia-1,14,15,16-tetraazahexacyclo[20.8.1.1 3,7 .1 9,13 .0 12,16 .0 24,29 ]tritriaconta-3,5,7(33),9,11,13(32),14,18,24(29),25,27-undecaen-8-yl}acetic acid; 
 2-{34-Methyl-3,3-dioxo-10-oxa-3λ 6 -thia-2,17,18,19-tetraazaheptacyclo[24.5.2.1 2,11 .1 20,24 .0 4,9 .0 17,21 .0 29,32 ]pentatriaconta-4(9),5,7,14,18,20(34),21,23,26(33),27,29(32)-undecaen-25-yl}acetic acid; 
 3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 
 (S)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; and 
 (R)-3-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-5-yl)-3-(3-(((R)-4-ethyl-1,1-dioxido-3,4-dihydro-2H-benzo[b][1,4,5]oxathiazepin-2-yl)methyl)-4-methylphenyl)-2,2-dimethylpropanoic acid; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         13 . A pharmaceutical composition comprising the compound or pharmaceutically acceptable salt according to  claim 1  and a pharmaceutically acceptable excipient. 
     
     
         14 . A method of treating respiratory and non-respiratory disorders, including COPD, asthma, fibrosis, chronic and acute asthma, lung disease secondary to environmental exposures, acute lung infection, chronic lung infection, α1 antitrypsin disease, cystic fibrosis, autoimmune diseases, diabetic nephropathy, chronic kidney disease, sepsis-induced acute kidney injury, acute kidney injury (AKI), kidney disease or malfunction seen during kidney transplantation, Pulmonary Arterial Hypertension, atherosclerosis, hypertension, heart failure, Parkinson's disease (PD), Alzheimer's disease (AD), autism, Friedreich's Ataxia (FA), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), inflammatory bowel disease, colon cancer, neovascular (dry) AMD and neovascular (wet) AMD, eye injury, Fuchs Endothelial Corneal Dystrophy (FECD), uveitis or other inflammatory eye conditions, Nonalcoholic Steatohepatitis (NASH), toxin-induced liver disease (e.g., acetaminophen-induced hepatic disease), viral hepatitis, cirrhosis, psoriasis, dermatitis/topical effects of radiation, immunosuppression due to radiation exposure, Preeclampsia, and high altitude sickness, which comprises administering to a human in need thereof, the compound or pharmaceutically acceptable salt according to  claim 1 . 
     
     
         15 . The method according to  claim 15  wherein the compound is administered orally. 
     
     
         16 . The method according to  claim 15  wherein the compound is administered intravenously. 
     
     
         17 . The method according to  claim 15  wherein the compound is administered by inhalation. 
     
     
         18 . The method according to  claim 15  wherein the disorder is COPD.