IP Library › Granted Patent US 9,777,018

Granted Patent B2

US 9,777,018 · App. 14/832,349 · Granted Oct 3, 2017

Compounds as modulators of GPR-119

Inventors: Dhanapalan Nagarathnam (La Chaux-de-Fonds, CH); Swaroop K. Vakkalanka (La Chaux-de-Fonds, CH); Srikant Viswanadha (Hyderabad, IN); Gayatri S. Merikapudi (Hyderabad, IN)

Assignee: RHIZEN PHARMACEUTICALS SA

C07D498/04 C07D401/04 C07D401/14 C07D405/04 C07D413/04 C07D413/14 C07D417/04 C07D417/14

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Quick Facts

Patent No.: US 9,777,018
App. No.: 14/832,349
Granted: Oct 3, 2017
Kind: B2

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Abstract

The present invention relates to novel compounds of formula (A) and (B) as modulators of GPR-119, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of GPR-119 mediated diseases or disorders with them.

Claims (276)

1. A method of treating a disease or disorder associated with the GPR119 receptor comprising administering to a subject in need of such treatment a compound of formula (A-I), (A-II), (B-I), (B-II), (B-III) and (B-IV):

or a tautomer, stereoisomer, enantiomer, diastereomer, salt, or N-oxide thereof,

wherein

Ar is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or Cy 1 ;

X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N; and X 4 is CR 4 or N;

X is CR or N;

Z is NR, CO, O or S(O) q ;

Cy 1 is selected from substituted or unsubstituted cycloalkyl or substituted or unsubstituted heterocyclic group;

each occurrence of R, R 1 , R 2 , R 3 and R 4 may be same or different and is independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 3-6 cycloalkylalkyl, substituted or unsubstituted C 3-6 cycloalkenyl, —OR a , —S(═O) q —R a , —NR a R b , —C(═Y)—R a , —CR a R b —C(═Y)—R a , —CR a R b —Y—CR a R b —, —C(═Y)—NR a R b —, —NR a —C(═Y)—NR a R b —, —S(═O) q —NR a R b —, —NR a —S(═O) q —NR a R b —, and —NR a —NR a R b —;

each occurrence of R a and R b may be same or different and are independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 3-6 cycloalkylalkyl, and substituted or unsubstituted C 3-6 cycloalkenyl, or when two R a and/or R b substituents are directly bound to a common atom, they may be joined to form (i) an oxo (═O), thio (═S) or imino (═NR d ), or (ii) a substituted or unsubstituted, saturated or unsaturated 3-10 member ring, which may optionally include one or more heteroatoms which may be same or different and are selected from O, NR c or S;

each occurrence of R c is independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 3-6 cycloalkylalkyl, and substituted or unsubstituted C 3-6 cycloalkenyl;

each occurrence of Y is independently selected from O, S, and NR a ; and

each occurrence of q independently represents 0, 1 or 2;

D and E are independently selected from CH or N;

R 5 is selected from hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio (═S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —COOR a , —C(O)R a , —C(S)R a , —C(O)NR a R b , —C(O)ONR a R b , —NR a R b , —NR a CONR a R b , —N(R a )SOR b , —N(R a )SO 2 R b , —(═N—N(R a )R b ), —NR a C(O)OR b , —NR a C(O)R b —, —NR a C(S)R b —NR a C(S)NR a R b , —SONR a R b —, —SO 2 NR a R b —, —OR a , —OR a C(O)NR a R b , —OR a C(O)OR b —, —OC(O)R a , —OC(O)NR a R b , —R a NR b C(O)R a , —R a OR b , —R a C(O)OR b , —R a C(O)NR a R b , —R a C(O)R b , —R a OC(O)R b , —SR a , —SOR a , —SO 2 R a , and —ONO 2 , or any two of R a and R b which are directly bound to a common atom may be joined to form (i) an oxo (═O), thio (═S) or imino (═NR d ), or (ii) a substituted or unsubstituted, saturated or unsaturated 3-14 member ring, which may optionally include one or more heteroatoms which may be same or different and are selected from O, NR d or S, wherein

each occurrence of R d is independently hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio (═S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclcyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, and —ONO 2 , or any two of R d which are directly bound to a common atom may be joined to form (i) a substituted or unsubstituted, saturated or unsaturated 3-14 membered ring, which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR′ (where R′ is H or alkyl) or S, or (ii) an oxo (═O), thio (═S) or imino (═NR′); and

each occurrence of R e , R f , R g , R h , R i , R j , R k and R l is independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 3-6 cycloalkylalkyl, and substituted or unsubstituted C 3-6 cycloalkenyl; or any two of R e , R f , R g , R h , R i , R j , R k , R l may be joined to form (i) a substituted or unsubstituted, saturated or unsaturated 3-14 membered ring, which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR′ (where R′ is H or alkyl) or S, or (ii) an oxo (═O), thio (═S) or imino (═NR′) (where R′ is H or alkyl); and

each of r, s, t and u is 0, 1 or 2 with the proviso that r+s+t+u≠0;

wherein the disease or disorder associated with the GPR119 receptor is selected from diabetes mellitus, a condition related to diabetes mellitus, type 1 , type 2 diabetes, inadequate glucose tolerance, impaired glucose tolerance, insulin resistance, hyperglycemia, and any combination thereof.

2. A method of treating a disease or disorder associated with the GPR119 receptor comprising administering to a subject in need of such treatment a compound of formula (A-III) and (A-IV):

or a tautomer, stereoisomer, enantiomer, diastereomer, salt, or N-oxide thereof,

wherein

Ar is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or Cy 1 ;

X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N; and X 4 is CR 4 or N;

X is CR or N;

Z is NR, CO, O or S(O) q ;

Cy 1 is selected from substituted or unsubstituted cycloalkyl or substituted or unsubstituted heterocyclic group;

each occurrence of Y is independently selected from O, S, and NR a ; and

each occurrence of q independently represents 0, 1 or 2;

D and E are independently selected from CH or N;

R 5 is selected from hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio (═S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —COOR a , ——C(O)R a , —C(S)R a , —C(O)NR a R b , —C(O)ONR a R b , —NR a R b , —NR a CONR a R b , —N(R a )SOR b , —N(R a )SO 2 R b , —(═N—N(R a )R b ), —NR a C(O)OR b , —NR a C(O)R b —, —NR a C(S)R b —NR a C(S)NR a R b , —SONR a R b —, —SO 2 NR a R b —, —OR a , —OR a C(O)NR a R b , —OR a C(O)OR b —, —OC(O)R a , —OC(O)NR a R b , —R a NR b C(O)R a , —R a OR b , —R a C(O)OR b , —R a C(O)NR a R b , —R a C(O)R b , —R a OC(O)R b , —SR a , —SOR a , —SO 2 R a , and —ONO 2 , or any two of R a and R b which are directly bound to a common atom may be joined to form (i) an oxo (═O), thio (═S) or imino (═NR d ), or (ii) a substituted or unsubstituted, saturated or unsaturated 3-14 member ring, which may optionally include one or more heteroatoms which may be same or different and are selected from O, NR d or S; wherein

each of r, s, t and u is 0, 1 or 2 with the proviso that r+s+t+u≠0,

with the proviso

a) that for compound of formula (A-III), wherein Z is O or S and X 4 is N or CR 4 then Ar cannot be

b) that for compound of formula (A-IV) wherein Z is O or S and X 1 is N or CR 1 then Ar cannot be

wherein

R 1 and R 4 is as defined above for compound of formula (A-III) and (A-IV);

W is S(═O) 2 —R 1 , S(═O) 2 —NR 1a R 1 , —C(═O)—R 1 , —C(═O)—O—R 1 , —C(═O)—NR 1a R 1 , —NR 1a —S(═O) 2 —R 1 , halo, or a 4 to 10-membered optionally substituted heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S;

R 1a , at each occurrence, is independently hydrogen or (C 1 -C 8 )alkyl; and

R 1 is optionally substituted (C 1 -C 6 )-alkyl, optionally substituted (C 2 -C 6 )-alkenyl, optionally substituted (C 2 -C 6 )-alkynyl, optionally substituted (C 3 -C 12 )-cycloalkyl, optionally substituted (C 1 -C 10 )aryl, a 4 to 10-membered optionally substituted heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S; or a 4 to 10-membered heterocyclyl, which contains 1-4 heteroatoms selected from N, O, and S;

3. The method of claim 1 , wherein Ar is selected from

4. The method of claim 1 , wherein

(a) Z is NH, N—CH 3 , O or S;

(b) X 1 is CR 1 or N, and R 1 is H or halogen;

(d) X 3 is CH;

(e) X 4 is CR 4 or N, and R 4 is H or halogen; and

(f) X is CR or N.

5. The method of claim 2 , wherein

(a) Z is O or S;

(b) X 1 is CR 1 or N, and R 1 is H or halogen;

(d) X 3 is CH;

(e) X 4 is CR 4 or N, and R 4 is H or halogen; and

(f) X is CR or N.

6. The method of claim 1 , wherein Cy 1 is selected from

7. A method of treating a disease or disorder associated with the GPR119 receptor comprising administering to a subject in need of such treatment a compound of formula (A-IA), (A-IIA), (B-IA), (B-IIA), (B-IIIA) or (B-IVA):

or a tautomer, stereoisomer, enantiomer, diastereomer, salt, or N-oxide thereof,

wherein

Ar is

G is independently selected from

R′ is substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or substituted or unsubstituted cycloalkyl;

X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N and X 4 is CR 4 or N;

X is CR or N;

each occurrence of Y is independently selected from O, S, and NR a ; and

each occurrence of q independently represents 0, 1 or 2;

R 6 is selected from hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —COOR a , —C(O)R a , —C(S)R a , —C(O)NR a R b , —C(O)ONR a R b , —NR a R b , —NR a CONR a R b , —N(R a )SOR b , —N(R a )SO 2 R b , —(═N—N(R a )R b ), —NR a C(O)OR b , —NR a C(O)R b —, —NR a C(S)R b —NR a C(S)NR a R b , —SONR a R b —, —SO 2 NR a R b —, —OR a , —OR a C(O)NR a R b , —OR a C(O)OR b —, —OC(O)R a , —OC(O)NR a R b , —R a NR b C(O)R a , —R a OR b , —R a C(O)OR b , —R a C(O)NR a R b , —R a C(O)R b , —R a OC(O)R b , —SR a , —SOR a , —SO 2 R a , and —ONO 2 ; and

p is 0, 1, 2, 3 or 4;

8. A method of treating a disease or disorder associated with the GPR119 receptor comprising administering to a subject in need of such treatment a compound of formula (A-IIIA) or (A-IVA)

wherein

Ar is

G is independently selected from

R′ is substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or substituted or unsubstituted cycloalkyl;

X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N and X 4 is CR 4 or N;

X is CR or N;

each occurrence of Y is independently selected from O, S, and NR a ; and

each occurrence of q independently represents 0, 1 or 2;

p is 0, 1, 2, 3 or 4,

with the proviso

a) that for compound of formula (A-IIIA), wherein Z is O or S and X 4 is N or CR 4 then Ar-G cannot be

b) that for compound of formula (A-IVA), wherein Z is O or S and X 1 is N or CR 1 then Ar-G cannot be

wherein

R 1 and R 4 is as defined above for compound of formula (A-IIIA) and (A-IVA);

R 1a , at each occurrence, is independently hydrogen or (C 1 -C 8 )alkyl;

9. The method of claim 7 , wherein

(a) X 1 is CR 1 or N and R 1 is H or halogen;

(b) X 2 is CH;

(d) X 4 is CR 4 or N, and R 4 is H or halogen;

(e) X is CR or N; and

(f) p is 0 or 1.

10. The method of claim 7 , wherein R 5 is selected from

11. The method of claim 10 , wherein R 5 is —C(O)OC(CH 3 ) 3 or —C(O)OCH(CH 3 ) 2 .

12. The method of claim 7 , wherein R 6 is halogen, substituted or unsubstituted alkyl or —OR a ; wherein R a is substituted or unsubstituted alkyl.

13. The method of claim 12 , wherein R 6 is —F, —CH 3 , —CF 3 or —OCH 3 .

14. The method of claim 7 , wherein Ar-G is selected from

15. The method of claim 14 , wherein G is independently selected from

16. The method of claim 14 , wherein X 1 is CH or CF; X is N or CH and Z is S or O.

17. The method of claim 16 , wherein X 1 is CH or CF; X is N or CH and Z is O.

18. The method of claim 8 , wherein

(a) X 1 is CR 1 or N and R 1 is H or halogen;

(b) X 2 is CH;

(d) X 4 is CR 4 or N, and R 4 is H or halogen;

(e) X is CR or N; and

(f) p is 0 or 1.

19. The method of claim 8 , wherein R 5 is selected from

20. The method of claim 19 , wherein R 5 is —C(O)OC(CH 3 ) 3 or —C(O)OCH(CH 3 ) 2 .

21. The method of claim 8 , where R 6 is halogen, substituted or unsubstituted alkyl or —OR a ; wherein R a is substituted or unsubstituted alkyl.

22. The method of claim 21 , wherein R 6 is —F, —CH 3 , —CF 3 or —OCH 3 .

23. The method of claim 8 , wherein Ar-G is selected from

24. The method of claim 23 , wherein G is independently selected from

25. The method of claim 23 , wherein X 1 is CH or CF; X is N or CH and Z is S or O.

26. The method of claim 25 , wherein X 1 is CH or CF; X is N or CH and Z is O.

27. A method of treating a disease or disorder associated with the GPR119 receptor comprising administering to a subject in need of such treatment a compound of formula (A-IB) and (A-IIB)

or a tautomer, stereoisomer, enantiomer, diastereomer, salt, or N-oxide thereof,

wherein

Z is O or S;

Ar1-G is

p is 0, 1-7 or 8;

G is selected from

R′ is substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or substituted or unsubstituted cycloalkyl;

X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N and X 4 is CR 4 or N;

X is CR or N;

each occurrence of Y is independently selected from O, S, and NR a ;

each occurrence of q independently represents 0, 1 or 2;

28. A method of treating a disease or disorder associated with the GPR119 receptor comprising administering to a subject in need of such treatment a compound of formula (A-IIIB) and (A-IVB)

or a tautomer, stereoisomer, enantiomer, diastereomer, salt, or N-oxide thereof,

wherein

Z is O or S;

Ar1-G is

p is 0, 1-7 or 8;

G is selected from

R′ is substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or substituted or unsubstituted cycloalkyl;

X 1 is CR 1 or N; X 2 is CR 2 or N; X 3 is CR 3 or N and X 4 is CR 4 or N;

X is CR or N;

each occurrence of R, R 1 , R 2 , and R 3 and R 4 may be same or different and is independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6 alkyl, substituted or unsubstituted C 2-6 alkenyl, substituted or unsubstituted C 2-6 alkynyl, substituted or unsubstituted C 3-6 cycloalkyl, substituted or unsubstituted C 3-6 cycloalkylalkyl, substituted or unsubstituted C 3-6 cycloalkenyl, —OR a , —S(═O) q —R a , —NR a R b , —C(═Y)—R a , —CR a R b —C(═Y)—R a , —CR a R b —Y—CR a R b —, —C(═Y)—NR a R b —, —NR a —C(═Y)—NR a R b —, —S(═O) q —NR a R b —, —NR a —S(═O) q —NR a R b —, and —NR a —NR a R b —;

each occurrence of Y is independently selected from O, S, and NR a ;

each occurrence of q independently represents 0, 1 or 2;

with the proviso

a) that for compound of formula (A-IIIB), wherein Z is O or S and X 4 is N or CR 4 then Ar1-G cannot be

b) that for compound of formula (A-IVB), wherein Z is O or S and X 1 is N or CR 1 then Ar1-G cannot be

wherein

R 1 and R 4 is as defined above for compound of formula (A-IIIB) and (A-IVB);

R 1a , at each occurrence, is independently hydrogen or (C 1 -C 8 )alkyl; and

R 1 is optionally substituted (C 1 -C 6 )-alkyl, optionally substituted (C 2 -C 6 )-alkenyl, optionally substituted (C 2 -C 6 )-alkynyl, optionally substituted (C 3 -C 12 )-cycloalkyl, optionally substituted (C 1 -C 10 )aryl, a 4- to 10-membered optionally substituted heteroaryl, which contains 1-4 heteroatoms selected from N, O, and S; or a 4 to 10-membered heterocyclyl, which contains 1-4 heteroatoms selected from N, O, and S;

29. A method of treating a disease or disorder associated with the GPR119 receptor comprising administering to a subject in need of such treatment a compound selected from

2-[1-(5-Ethylpyrimidin-2-yl)piperidin-4-yl]-5-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-benzo[d]imidazole;

Tert-butyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-benzo[d]imidazol-2-yl}piperidine-1-carboxylate;

2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-5-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole;

Tert-butyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]-1-methyl-1H-benzo[d]imidazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-{6-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-{5-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-{7-fluoro-5-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-[5-(4-cyanophenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Tert-butyl 4-{5-[3-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-{5-[4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-{5-[4-(trifluoromethyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-{5-[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

2-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazole;

Tert-butyl 4-[5-(4-cyano-3-fluorophenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Isopropyl 4-{5-[3-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-{5-[3-fluoro-4-(1H-tetrazol-5-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Tert-butyl 4-[5-(4-carbamoyl-3-chlorophenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Tert-butyl 4-[5-(4-carbamoyl-3-fluorophenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Tert-butyl 4-[5-(3-fluoro-4-isopropoxyphenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Cyclobutyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Sec-butyl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Pentan-3-yl 4-{5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-(piperidin-4-yl)benzo[d]oxazole;

Isopropyl 4-{5-[4-(trifluoromethyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-[5-(4-formylphenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Isopropyl 4-{5-[4-(difluoromethyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-[5-(4-carbamoyl-3-chlorophenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Isopropyl 4-[5-(4-carbamoyl-3-fluorohenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

1-{4-[5-(2-fluoro-4-(1H-tetrazol-1-yl)phenyl)benzo[d]oxazol-2-yl]piperidin-1-yl}-2-methylpropan-1-one;

Isopropyl 4-{6-[4-(difluoromethyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

6-{2-[1-(isopropoxycarbonyl)piperidin-4-yl]benzo[d]oxazol-5-yl}nicotinic acid;

5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-[1-(methylsulfonyl)piperidin-4-yl]benzo[d]oxazole;

Isopropyl 4-[5-(5-carbamoylpyridin-2-yl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Isopropyl 4-[5-(4-carbamoyl-2-fluorophenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Isopropyl 4-[5-(4-carbamoyl-2-chlorophenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

2-Fluoro-4-{2-[1-(3-methylbutanoyl)piperidin-4-yl]benzo[d]oxazol-5-yl}benzamide;

1-{4-[5-(2-fluoro-4-(1H-tetrazol-1-yl)phenyl]benzo[d]oxazol-2-yl]piperidin-1-yl}-3-methylbutan-1-one;

5-[2-fluoro-4-(1H-tetrazol-1-yl)phenyl]-2-[1-(2-methoxyethyl)piperidin-4-yl]benzo[d]oxazole;

Isopropyl 4-{5-[3-fluoro-4-(methylcarbamoyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

2-Fluoro-4-[2-(1-isobutyrylpiperidin-4-yl)benzo[d]oxazol-5-yl]benzamide;

Isopropyl 4-[6-(4-carbamoyl-3-fluorophenyl)benzo[d]oxazol-2-yl]piperidine-1-carboxylate;

Isopropyl 4-{5-[3-fluoro-4-(2-hydroxyethylcarbamoyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-{5-[3-fluoro-4-(isopropylcarbamoyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-{5-[4-(N-methylsulfamoyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-{5-[6-(methylcarbamoyl)pyridin-3-yl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-{5-[3-methyl-4-(methylcarbamoyl)phenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

Isopropyl 4-{5-[4-(cyclopropylcarbamoyl)-3-fluorophenyl]benzo[d]oxazol-2-yl}piperidine-1-carboxylate;

2-Fluoro-4-{2-[1-(5-fluoropyrimidin-2-yl)piperidin-4-yl]benzo[d]oxazol-5-yl}benzamide;

Tert-butyl 4-[5-(4-carbamoyl-3-fluorophenyl)benzofuran-2-yl]-5,6-dihydropyridine-1(2H)-carboxylate;

2-fluoro-4-{2-[1-(propylsulfonyl)piperidin-4-yl]benzo[d]oxazol-5-yl}benzamide;

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-benzo[d]imidazol-5-yl}-5,6-dihydropyridine-1(2H)-carboxylate;

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-benzo[d]imidazol-5-yl}piperidine-1-carboxylate;

5-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-2-[2-fluoro-4-(methylsulfonyl)phenyl]-1H-benzo[d]imidazole;

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}-5,6-dihydropyridine-1(2H)-carboxylate;

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperidine-1-carboxylate;

2-[2-fluoro-4-(methylsulfonyl)phenyl]-5-(piperidin-4-yl)benzo[d]oxazole 2,2,2-trifluoro acetate;

5-[1-(5-ethylpyrimidin-2-yl)piperidin-4-yl]-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazole;

Tert-butyl 4-{7-fluoro-2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperidine-1-carboxylate;

Isopropyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperidine-1-carboxylate;

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]thiazol-6-yl}-5,6-dihydropyridine-1(2H)-carboxylate;

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]thiazol-5-yl}-5,6-dihydropyridine-1(2H)-carboxylate;

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-6-yl}piperidine-1-carboxylate;

Tert-butyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]thiazol-5-yl}piperidine-1-carboxylate;

Ethyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperidine-1-carboxylate;

Tert-butyl 4-{2-[4-(trifluoromethyl)phenyl]benzo[d]oxazol-5-yl}piperidine-1-carboxylate;

Isopropyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-6-yl}piperidine-1-carboxylate;

Ethyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-6-yl}piperidine-1-carboxylate;

Benzyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperidine-1-carboxylate;

Isobutyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperidine-1-carboxylate;

Isopropyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]thiazol-6-yl}piperidine-1-carboxylate;

Isopropyl 4-{2-[4-(trifluoromethyl)phenyl]benzo[d]oxazol-5-yl}piperidine-1-carboxylate;

Isopropyl 4-(2-p-tolylbenzo[d]oxazol-6-yl)piperidine-1-carboxylate;

3-{4-[2-(2-fluoro-4-(methylsulfonyl)phenyl)benzo[d]oxazol-5-yl]-5,6-dihydropyridin-1(2H)-ylsulfonyl}propan-1-ol;

3-{4-[2-(2-fluoro-4-(methylsulfonyl)phenyl)benzo[d]oxazol-5-yl]piperidin-1-ylsulfonyl}propan-1-ol;

Tert-butyl 4-[2-(4-carbamoyl-3-fluorophenyl)benzo[d]oxazol-5-yl]piperidine-1-carboxylate;

2-[2-fluoro-4-(methylsulfonyl)phenyl]-5-[4-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-1-yl]benzo[d]oxazole;

Tert-butyl 4-{2-[4-(trifluoromethyl)phenyl]benzo[d]oxazol-6-yl}piperidine-1-carboxylate

Isopropyl 4-{2-[2-fluoro-4-(methylsulfonyl)phenyl]benzo[d]oxazol-5-yl}piperazine-1-carboxylate;

Tert-butyl 4-{2-[4-(trifluoromethyl)phenyl]oxazolo[5,4-b]pyridin-6-yl}-5,6-dihydropyridine-1(2H)-carboxylate;

Tert-butyl 4-{2-[4-(trifluoromethyl)phenyl]oxazolo[5,4-b]pyridin-6-yl}piperidine-1-carboxylate;

and pharmaceutically acceptable salts thereof;

30. The method according to claim 1 , wherein the disease or disorder associated with the GPR119 receptor is diabetes mellitus.

31. The method according to claim 2 , wherein the disease or disorder associated with the GPR119 receptor is diabetes mellitus.

32. The method according to claim 7 , wherein the disease or disorder associated with the GPR119 receptor is diabetes mellitus.

33. The method according to claim 8 , wherein the disease or disorder associated with the GPR119 receptor is diabetes mellitus.

34. The method according to claim 27 , wherein the disease or disorder associated with the GPR119 receptor is diabetes mellitus.

35. The method according to claim 28 , wherein the disease or disorder associated with the GPR119 receptor is diabetes mellitus.

36. The method according to claim 29 , wherein the disease or disorder associated with the GPR119 receptor is diabetes mellitus.

Assignments (1)

CHANGE OF ADDRESS Recorded Mar 22, 2021

From: RHIZEN PHARMACEUTICALS SA

To: RHIZEN PHARMACEUTICALS SA

Reel/Frame 056775/0375 →

Priority Claims (5)

IN 1958/CHE/2011 · Jun 9, 2011 · national

IN 2352/CHE/2011 · Jul 11, 2011 · national

IN 3462/CHE/2011 · Oct 7, 2011 · national

IN 3463/CHE/2011 · Oct 7, 2011 · national

IN 82/CHE/2012 · Jan 9, 2012 · national

Continuity (4)

Continuation 13492309 · Jun 8, 2012

Provisional Application 61543152 · Oct 4, 2011

Provisional Application 61543157 · Oct 4, 2011

Related Publication 20150361092A1 · Dec 17, 2015