Prostaglandin E2 (PGE2) EP4 receptor antagonists

A compound of the following formula (I)

• wherein:
• A1 and A2 are each independently C1-5 alkyl;
• ring B is a carbocyclic group or a heterocyclic group;
• ring D is carbocyclyl or heterocyclyl;
• L is-heterocyclylene-(CH2)1-2—, wherein one —CH2— unit comprised in said-heterocyclylene-(CH2)1-2— is optionally replaced by a group selected from —O13 , —CO—, —NH—, —N(C1-5 alkyl)-and-N [—CO—(C1-5 alkyl)]-, wherein the heterocyclylene in said-heterocyclylene-(CH2)1-2— is optionally substituted with one or more groups -LA-RA, and further wherein L is attached to ring D via —CH2— r via —O— contained in said L;
• m is an integer of 0 to 4;
• p is an integer of 0 to 4;
• R2 is selected from hydrogen, C1-5 alkyl, and —CO(C1-5 alkyl);
• X is C(R3a)(R3b) or N(R3c);
• R3a is selected from C1-5 alkyl and C2-5 alkenyl, and R3b is selected from hydrogen, C1-5 alkyl, and C2-5 alkenyl;
• or R3a and R3b are mutually linked to form, together with the carbon atom that they are attached to, a cycloalkyl or a heterocycloalkyl, wherein said cycloalkyl or said heterocycloalkyl is optionally substituted with one or more groups R31;
• or R3a is a divalent group selected from linear C2-4 alkylene and linear C2-4 alkenylene, wherein said divalent group is attached via one end to the carbon atom carrying R3b and is attached via the other end to a ring atom of ring B which is adjacent to the ring atom carrying the group X, wherein said alkylene or said alkenylene is optionally substituted with one or more groups R31, wherein one —CH2— unit in said alkylene or said alkenylene is optionally replaced by —O—, —S—, —NH— or —N(C1-5 alkyl)-, and R3b is selected from hydrogen, C1-5 alkyl, and C2-5 alkenyl;
• R3c is selected from hydrogen, C1-5 alkyl, and C2-5 alkenyl;
• each R31 is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, —OH, —O(C1-5 alkyl), —O(C1-5 alkylene)-OH, —O(C1-5 alkylene)-O(C1-5 alkyl), —SH, —S(C1-5 alkyl), —S(C1-5 alkylene)-SH, —S(C1-5 alkylene)-S(C1-5 alkyl), —NH2, —NH(C1-5 alkyl), —N(C1-5 alkyl) (C1-5 alkyl), halogen, C1-5 haloalkyl, —O—(C1-5 haloalkyl), —CN, —CHO, —CO—(C1-5 alkyl), —COOH, —CO—O—(C1-5 alkyl), —O—CO—(C1-5 alkyl), —CO—NH2, —CO—NH(C1-5 alkyl), —CO—N(C1-5 alkyl) (C1-5 alkyl), —NH—CO—(C1-5 alkyl), —N(C1-5 alkyl)-CO—(C1-5 alkyl), —NH—COO(C1-5 alkyl), —N(C1-5 alkyl)-COO(C1-5 alkyl), —O—CO—NH(C1-5 alkyl), —O—CO—N(C1-5 alkyl) (C1-5 alkyl), —SO2—NH2, —SO2—NH(C1-5 alkyl), —SO2—N(C1-5 alkyl) (C1-5 alkyl), —NH—SO2—(C1-5 alkyl), —N(C1-5 alkyl)-SO2—(C1-5 alkyl), —SO—(C1-5 alkyl), and —SO2—(C1-5 alkyl);
• each R4 is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, —(C0-3 alkylene)-OH, —(C0-3 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-O(C1-5 alkylene)-OH, —(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-S(C1-5 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-NH2, —(C0-3 alkylene)-NH(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-halogen, —(C0-3 alkylene)-(C1-5 haloalkyl), —(C0-3 alkylene)-O—(C1-5 haloalkyl), —(C0-3 alkylene)-CN, —(C0-3 alkylene)-CHO, —(C0-3 alkylene)-CO—(C1-5 alkyl), —(C0-3 alkylene)-COOH, —(C0-3 alkylene)-CO—O—(C1-5 alkyl), —(C0-3 alkylene)-O—CO—(C1-5 alkyl), —(C0-3 alkylene)-CO—NH2, —(C0-3 alkylene)-CO—NH(C1-5 alkyl), —(C0-3 alkylene)-CO—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-NH—CO—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-CO—(C1-5 alkyl), —(C0-3 alkylene)-NH—COO(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-COO(C1-5 alkyl), —(C0-3 alkylene)-O—CO—NH(C1-5 alkyl), —(C0-3 alkylene)-O—CO—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-SO2—NH2, —(C0-3 alkylene)-SO2—NH(C1-5 alkyl), —(C0-3 alkylene)-SO2—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-NH—SO2—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-SO2—(C1-5 alkyl), —(C0-3 alkylene)-SO—(C1-5 alkyl), —(C0-3 alkylene)-SO2—(C1-5 alkyl), —(C0-3 alkylene)-cycloalkyl, —(C0-3 alkylene)-heterocycloalkyl, and -LA-RA;
• R5 is selected from —COOH, —CO—NH2, —CO—NH(C1-5 alkyl), —CO—N(C1-5 alkyl) (C1-5 alkyl), —SO2—OH, —SO2—O—(C1-5 alkyl), —SO2—NH2, —SO2—NH(C1-5 alkyl), —SO2—N(C1-5 alkyl) (C1-5 alkyl), —SO2—(C1-5 alkyl), —S(═O) (=NH)—(C1-5 alkyl), halogen, C1-5 haloalkyl, —CN, C1-4 alkyl, —OH, —O(C1-4 alkyl), carbocyclyl, and heterocyclyl, wherein said carbocyclyl or said heterocyclyl is optionally substituted with one or more groups-LA-RA;
• each R6 is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, —(C0-3 alkylene)-OH, —(C0-3 alkylene)-O(C1-6 alkyl), —(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-OH, —(C0-3 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-S(C1-5 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-NH2, —(C0-3 alkylene)-NH(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-halogen, —(C0-3 alkylene)-(C1-5 haloalkyl), —(C0-3 alkylene)-O—(C1-5 haloalkyl), —(C0-3 alkylene)-CN, —(C0-3 alkylene)-CHO, —(C0-3 alkylene)-CO—(C1-5 alkyl), —(C0-3 alkylene)-COOH, —(C0-3 alkylene)-CO—O—(C1-5 alkyl), —(C0-3 alkylene)-O—CO—(C1-5 alkyl), —(C0-3 alkylene)-CO—NH2, —(C0-3 alkylene)-CO—NH(C1-5 alkyl), —(C0-3 alkylene)-CO—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-NH—CO—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-CO—(C1-5 alkyl), —(C0-3 alkylene)-NH—COO(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-COO(C1-5 alkyl), —(C0-3 alkylene)-O—CO—NH(C1-5 alkyl), —(C0-3 alkylene)-O—CO—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-SO2—NH2, —(C0-3 alkylene)-SO2—NH(C1-5 alkyl), —(C0-3 alkylene)-SO2—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-NH—SO2—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-SO2—(C1-5 alkyl), —(C0-3 alkylene)-SO—(C1-5 alkyl), —(C0-3 alkylene)-SO2—(C1-5 alkyl), —(C0-3 alkylene)-cycloalkyl, —(C0-3 alkylene)-heterocycloalkyl, and -L1-R61;
• L1 is C1-6 alkylene or a covalent bond, wherein one or more —CH2— units comprised in said C1-6 alkylene are each optionally replaced by a group independently selected from —O—, —CO—, —NH—, —N(C1-5 alkyl)-, —N [—CO—(C1-5 alkyl)]-, —S—, —SO—, —SO2—, —CH(C1-5 alkyl)-and-C(C1-5 alkyl) (C1-5 alkyl)-;
• R61 is carbocyclyl or heterocyclyl, wherein said carbocyclyl or said heterocyclyl is optionally substituted with one or more groups R62;
• each R62 is independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, —(C0-3 alkylene)-OH, —(C0-3 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-O(C1-5 alkylene)-OH, —(C0-3 alkylene)-O(C1-5 alkylene)-O(C1-5 alkyl), —(C0-3 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-S(C1-5 alkylene)-SH, —(C0-3 alkylene)-S(C1-5 alkylene)-S(C1-5 alkyl), —(C0-3 alkylene)-NH2, —(C0-3 alkylene)-NH(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-halogen, —(C0-3 alkylene)-(C1-5 haloalkyl), —(C0-3 alkylene)-O—(C1-5 haloalkyl), —(C0-3 alkylene)-CN, —(C0-3 alkylene)-CHO, —(C0-3 alkylene)-CO—(C1-5 alkyl), —(C0-3 alkylene)-COOH, —(C0-3 alkylene)-CO—O—(C1-5 alkyl), —(C0-3 alkylene)-O—CO—(C1-5 alkyl), —(C0-3 alkylene)-CO—NH2, —(C0-3 alkylene)-CO—NH(C1-5 alkyl), —(C0-3 alkylene)-CO—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-NH—CO—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-CO—(C1-5 alkyl), —(C0-3 alkylene)-NH—COO(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-COO(C1-5 alkyl), —(C0-3 alkylene)-O—CO—NH(C1-5 alkyl), —(C0-3 alkylene)-O—CO—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-SO2—NH2, —(C0-3 alkylene)-SO2—NH(C1-5 alkyl), —(C0-3 alkylene)-SO2—N(C1-5 alkyl) (C1-5 alkyl), —(C0-3 alkylene)-NH—SO2—(C1-5 alkyl), —(C0-3 alkylene)-N(C1-5 alkyl)-SO2—(C1-5 alkyl), —(C0-3 alkylene)-SO—(C1-5 alkyl), —(C0-3 alkylene)-SO2—(C1-5 alkyl), —(C0-3 alkylene)-cycloalkyl, and —(C0-3 alkylene)-heterocycloalkyl;
• each LA is independently selected from a covalent bond, C1-5 alkylene, C2-5 alkenylene, and C2-5 alkynylene, wherein said alkylene, said alkenylene and said alkynylene are each optionally substituted with one or more groups independently selected from halogen, C1-5 haloalkyl, —CN, —OH, —O(C1-5 alkyl), —SH, —S(C1-5 alkyl), —NH2, —NH(C1-5 alkyl), and —N(C1-5 alkyl) (C1-5 alkyl), and further wherein one or more —CH2— units comprised in said alkylene, said alkenylene or said alkynylene are each optionally replaced by a group independently selected from —O—, —NH—, —N(C1-5 alkyl)-, —CO—, —S—, —SO—, and —SO2—;
• and
• each RA is independently selected from —OH, —O(C1-5 alkyl), —O(C1-5 alkylene)-OH, —O(C1-5 alkylene)-O(C1-5 alkyl), —SH, —S(C1-5 alkyl), —S(C1-5 alkylene)-SH, —S(C1-5 alkylene)-S(C1-5 alkyl), —NH2, —NH(C1-5 alkyl), —N(C1-5 alkyl) (C1-5 alkyl), halogen, C1-5 haloalkyl, —O(C1-5 haloalkyl), —CN, —CHO, —CO(C1-5 alkyl), —COOH, —COO(C1-5 alkyl), —O—CO(C1-5 alkyl), —CO—NH2, —CO—NH(C1-5 alkyl), —CO—N(C1-5 alkyl) (C1-5 alkyl), —NH—CO(C1-5 alkyl), —N(C1-5 alkyl)-CO(C1-5 alkyl), —NH—COO(C1-5 alkyl), —N(C1-5 alkyl)-COO(C1-5 alkyl), —O—CO—NH(C1-5 alkyl), —O—CO—N(C1-5 alkyl) (C1-5 alkyl), —SO2—NH2, —SO2—NH(C1-5 alkyl), —SO2—N(C1-5 alkyl) (C1-5 alkyl), —NH—SO2—(C1-5 alkyl), —N(C1-5 alkyl)-SO2—(C1-5 alkyl), —SO2—(C1-5 alkyl), —SO—(C1-5 alkyl), hydrogen, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl, wherein said aryl, said heteroaryl, said cycloalkyl, and said heterocycloalkyl are each optionally substituted with one or more groups independently selected from C1-5 alkyl, C2-5 alkenyl, C2-5 alkynyl, halogen, C1-5 haloalkyl, —CN, —OH, —O(C1-5 alkyl), —SH, —S(C1-5 alkyl), —NH2, —NH(C1-5 alkyl), and —N(C1-5 alkyl) (C1-5 alkyl);
• or a pharmaceutically acceptable salt thereof.