Cyclohexyl and quinuclidinyl carbamate derivatives having β2 adrenergic agonist and M3 muscarinic antagonist activity

A compound of Formula (A), or a pharmaceutically acceptable salt or deuterated derivative thereof:

• wherein:
• R is chosen from the group consisting of a hydrogen atom, a halogen atom, a hydroxyl group, a linear or branched C1-4 alkyl group, a linear or branched C1-4 hydroxyalkyl group, and a linear or branched C1-4 alkoxy group,
• n is lor 2,
• R1 is:
• wherein:
• R2 and R3 are independently chosen from a hydrogen atom, a linear or branched C1-4 alkyl group, a (C5-6 aryl)-(C1-4)alkyl group, and a linear or branched C1-4 alkoxy group,
• R′ is chosen from a hydrogen atom or a linear or branched C1-4 alkyl group,
• * is a point of attachment of R1 to the remainder of the molecule of Formula (A),
• Lx is a suitable covalent linker, and
• B represents a group of Formula (IB):
• wherein:
• R4 is chosen from the group consisting of a hydrogen atom, a linear or branched C1-4 alkyl group, and a linear or branched C1-4 alkoxy group,
• Ar is chosen from the group consisting of a C3-10 saturated or unsaturated, mono- or bicyclic cycloalkyl group;
• a C5-C14 mono- or bicyclic aryl group;
• a 3 to 14-membered saturated or unsaturated mono- or bicyclic heterocyclyl group having one or more heteroatoms chosen from N, S, and O;
• and a 5- to 14-membered mono- or bicyclic heteroaryl group having one or more heteroatoms chosen from N, S, and O;
• and wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a cyano group, a nitro group, an oxo group, a carboxy group, a C1-4 alkyl group, a C1-4 alkoxy group, —CF3, —OCF3, —NReRf, —(CH2)p—OH, —NRe(CO)Rf, —NRe—SO2—Rg, —SO2NReRf, —OC(O)Rh, and —NRe(CH2)(0-2)—Ri, wherein p is 0, 1 or 2 and wherein:
• Re and Rf are independently chosen from a hydrogen atom and a linear or branched C1-4 alkyl group,
• Rg is chosen from the group consisting of a linear or branched C1-4 alkyl group, a C5-6 aryl group, and a saturated or unsaturated C3-8 cycloalkyl, wherein the cyclic groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group, and a C1-4 alkoxy group, Rh is chosen from a hydrogen atom, —NReRf, and a C5-6 aryl group, which is optionally substituted with one or more substituents chosen from a C1-4 alkyl group and a C1-4 alkoxy group,
• Ri is chosen from the group consisting of a C5-6 aryl group, a C3-8 cycloalkyl group, and a 3 to 8 membered saturated or unsaturated heterocyclyl group, which groups independently are optionally substituted with one or more substituents chosen from a halogen atom, a C1-4 alkyl group, and a C1-4 alkoxy group.