Cyclic amide derivative
AssigneeMochida Pharmaceutical Co., Ltd.
InventorsAkihiro OKANO, Munetaka OHKOUCHI, Muneyoshi MAKABE
Life of this patent
Estimating the term…
Abstract
[Problem] To provide a GPR40 activating agent having, as an active ingredient, a novel compound having a GPR40 agonist action, a salt of the compound, a solvate of the salt or the compound, or the like, particularly, an insulin secretagogues and a prophylactic and/or therapeutic agent against diabetes, obesity, or other diseases. Means of Solving the Problem A compound of Formula (I): (where n is 0 to 2; p is 0 to 4; h is 0 to 3; j is 0 to 3; k is 0 to 2; a ring B is an aryl group or a heteroaryl group; X is O, S, or —NR7—; J1 is —CR11aR11b— or —NR11c; J2 is —CR12aR12b— or —NR12c—; and R1 to R12c are specific groups), a salt of the compound, or a solvate of the salt or the compound.
Claims19
A compound of Formula (I):
- (wherein n is an integer of 0 to 2;
- p is an integer of 0 to 4;
- h is an integer of 0 to 3;
- j is an integer of 0 to 3;
- k is an integer of 0 to 2;
- a ring A is a C6-14 aryl group which is optionally substituted with 1 to 5 L(s), a 3- to 14-membered heterocyclic group which is optionally substituted with 1 to 5 L(s), a C5-7 cycloalkyl group which is optionally substituted with 1 to 5 L(s), a C5-7 cycloalkenyl group which is optionally substituted with 1 to 5 L(s), a 6- to 14-membered spiro ring group which is optionally substituted with 1 to 5 L(s), or a 2-phenylamino-2-oxoacetyl group which is optionally substituted with 1 to 5 L(s);
- a ring B is a C6-14 aryl group or a 5- to 14-membered heteroaryl group;
- X is an oxygen atom, a sulfur atom, or —NR7—;
- J1 is —CR11aR11b— or —NR11c;
- J2 is —CR12aR12b— or —NR12c— (with the proviso that when J1 is —NR11c—, h is 0);
- R1s are independently a group optionally selected from a halogen atom, a C1-6 alkyl group which is optionally substituted with 1 to 5 substituent(s) RI, a C2-6 alkenyl group which is optionally substituted with 1 to 5 substituent(s) RI, a C2-6 alkynyl group which is optionally substituted with 1 to 5 substituent(s) RI, a C1-6 alkoxy group which is optionally substituted with 1 to 5 substituent(s) RI, and a cyano group;
- R2a and R2b are independently a group optionally selected from a hydrogen atom, a halogen atom, a C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group, and a cyano group;
- R3, R4, R5, R6, and R7 are independently a group optionally selected from a hydrogen atom, a C1-6 alkyl group, a halogenated C1-6 alkyl group, a C2-6 alkenyl group, and a C2-6 alkynyl group;
- R11a and R11b are independently a group optionally selected from a hydrogen atom, a halogen atom, a C1-6 alkyl group, a halogenated C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group, a halogenated C1-6 alkoxy group, a C2-7 alkanoyl group, and a carboxy group which is optionally protected;
- R12a and R12b are independently a group optionally selected from a hydrogen atom, a halogen atom, a C1-6 alkyl group, a halogenated C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C1-6 alkoxy group, a halogenated C1-6 alkoxy group, and a cyano group;
- R11C and R12c are independently a group optionally selected from a hydrogen atom, a C1-6 alkyl group, and a halogenated C1-6 alkyl group;
- with the proviso that in the cyclic amide structure moiety, there is not one of the substituents (R2b, R11b, R11c, R12b, or R12c) on an atom to which the ring B is bonded;
- Ls are independently a group optionally selected from a halogen atom, —OH, an oxo group, a cyano group, a C1-10 alkyl group which is optionally substituted with 1 to 5 substituent(s) RI, a C2-10 alkenyl group which is optionally substituted with 1 to 5 substituent(s) RI, a C2-10 alkynyl group which is optionally substituted with 1 to 5 substituent(s) RI, a C1-10 alkoxy group which is optionally substituted with 1 to 5 substituent(s) RI, a C2-10 alkenyloxy group which is optionally substituted with 1 to 5 substituent(s) RI, a C2-10 alkynyloxy group which is optionally substituted with 1 to 5 substituent(s) RI, an aryl group which is optionally substituted with 1 to 5 substituent(s) RII, a heterocyclic group which is optionally substituted with 1 to 5 substituent(s) RII, an aralkyl group which is optionally substituted with 1 to 5 substituent(s) RII, a heteroarylalkyl group which is optionally substituted with 1 to 5 substituent(s) RII, a non-aromatic heterocyclic alkyl group which is optionally substituted with 1 to 5 substituent(s) RII, an aryloxy group which is optionally substituted with 1 to 5 substituent(s) RII, a heteroaryloxy group which is optionally substituted with 1 to 5 substituent(s) RII, a non-aromatic heterocyclic oxy group which is optionally substituted with 1 to 5 substituent(s) RII, an aralkyloxy group which is optionally substituted with 1 to 5 substituent(s) RII, a heteroarylalkyloxy group which is optionally substituted with 1 to 5 substituent(s) RII, —SH, —SF5, a —S(O)iRa (i is an integer of 0 to 2) group, a —NRbRc group, and a substituted spiropiperidinylmethyl group;
- Ra is a C1-6 alkyl group or a halogenated C1-6 alkyl group;
- Rb and Rc are independently a group optionally selected from a hydrogen atom, a C1-6 alkyl group, a halogenated C1-6 alkyl group, a C2-6 alkenyl group, a C2-6 alkynyl group, a C2-7 alkanoyl group (the alkanoyl group is optionally substituted with —OH or a C1-6 alkoxy group), a C1-6 alkylsulfonyl group, an arylcarbonyl group, and a heterocyclic carbonyl group, where Rb and Rc optionally form together with a nitrogen atom to which they are bonded, a 3- to 8-membered cyclic group, where in the cyclic group, one or two carbon atom(s) is(are) optionally substituted with an atom optionally selected from an oxygen atom, a sulfur atom, and a nitrogen atom (the nitrogen atom is optionally substituted with a C1-6 alkyl group which is optionally substituted with 1 to 5 substituent(s) RI) or with a carbonyl group, and the cyclic group is optionally further substituted with 1 to 5 substituent(s) RII;
- where the substituents RI are the same as or different from each other and are each a group optionally selected from a halogen atom, —OH, a cyano group, a C1-6 alkoxy group (the C1-6 alkoxy group is optionally substituted with 1 to 5 halogen atom(s), 1 to 5 —OH, 1 to 5 C1-6 alkoxy group(s), 1 to 5 aryl group(s) (the aryl group is optionally substituted with 1 to 3 halogen atom(s)), 1 to 5 heterocyclic group(s) (the heterocyclic group is optionally substituted with 1 to 3 C1-6 alkyl group(s) or 1 to 3 oxo group(s)), 1 to 5 —S(O)iRa (i is an integer of 0 to 2) group(s), 1 to 5 —SO2NRdRe group(s), 1 to 5 —CONRdRe group(s), or 1 to 5 —NRb1Rc1 group(s)), a —NRb1Rc1 group, and a heterocyclic oxy group (the heterocyclic oxy group is optionally substituted with 1 to 3 C1-6 alkyl group(s) or 1 to 3 oxo group(s));
- the substituents RII are the same as or different from each other and are each a group optionally selected from the substituents RI, a C1-6 alkyl group (the C1-6 alkyl group is optionally substituted with 1 to 5 halogen atom(s), 1 to 5 —OH, 1 to 5 C1-6 alkoxy group(s), 1 to 5 —S(O)iRa (i is an integer of 0 to 2) group(s), 1 to 5 —NRb1Rc1 group(s), 1 to 5 —SO2NRdRe group(s), or 1 to 5 —CONRdRe group(s)), a C2-6 alkenyl group, a C2-7 alkanoyl group, an aralkyloxy group, a heterocyclic group (the heterocyclic group is optionally substituted with 1 to 3 C1-6 alkyl group(s) or 1 to 3 oxo group(s)), a heterocyclic carbonyl group (the heterocyclic carbonyl group is optionally substituted with 1 to 3 C1-6 alkyl group(s) or 1 to 3 oxo group(s)), a —S(O)iRa (i is an integer of 0 to 2) group, a —CONRdRe group, and a —CONRdRe l group;
- Rd and Re are independently a hydrogen atom or a C1-6 alkyl group (the C1-6 alkyl group is optionally substituted with 1 to 5 halogen atom(s), 1 to 5 —OH, or 1 to 5 C1-6 alkoxy group(s));
- Re1 is a C1-6 alkyl group (the C1-6 alkyl group is substituted with 1 to 5 —OH, 1 to 5 C1-6 alkoxy group(s), 1 to 5 aryl group(s) (the aryl group is optionally substituted with 1 to 3 halogen atom(s)), 1 to 5 heterocyclic group(s) (the heterocyclic group is optionally substituted with 1 to 3 C1-6 alkyl group(s) or 1 to 3 oxo group(s)), 1 to 5 —S(O)iRa (i is an integer of 0 to 2) group(s), 1 to 5 —SO2NRdRe group(s), 1 to 5 —CONRdRe group(s), or 1 to 5 —NRb1Rc1 group(s));
- Rb1 and Re1 are independently a group optionally selected from a hydrogen atom, a C1-6 alkyl group, a C2-7 alkanoyl group, and a C1-6 alkylsulfonyl group, where Rb1 and Rc1 optionally form together with a nitrogen atom to which they are bonded, a 3- to 8-membered cyclic group, where in the cyclic group, one or two carbon atom(s) is(are) optionally substituted with an atom optionally selected from an oxygen atom, a sulfur atom, and a nitrogen atom (the nitrogen atom is optionally substituted with a C1-6 alkyl group) or with a carbonyl group (with the proviso that there are excluded a compound which is 5-[4-[2-(2-phenyl-4-oxazolyl)ethoxy]phenyl]-1,1-dioxo-1,2,5-thiadiazolidin-3-one;
- a compound in which:
- a saturated cyclic amide structure having —S(O)n—NH—CO— is 1,1-dioxo-1,2-thiazolidin-3-one;
- the ring B is a benzene ring;
- the ring B is bonded to J1;
- k is 1;
- and in the ring B, a linker moiety containing X and the cyclic amide structure are positioned at a p-position;
- and a compound in which:
- the cyclic amide structure is 1,1-dioxo-1,2,5-thiadiazolidin-3-one;
- the ring B is bonded to J1;
- and in the ring B, the cyclic amide structure is bonded to an atom adjacent to an atom to which a linker containing X is bonded),
- a pharmaceutically acceptable salt of the compound, or a pharmaceutically acceptable solvate of the compound or a pharmaceutically acceptable solvate of the salt.
12-14. (canceled)
Dependencies are inferred from the claim text.