Cyclohexyl or heterocycloalkyl beta-hydroxy alkyl amines for use in the treatment of hyperglycaemia and disorders characterised by hyperglycaemia

A compound of formula I

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 represents H or C1-6 alkyl;
• each of Q1 to Q5 independently represent carbon, a heteroatom or a direct bond such that the ring comprising Q1 to Q5 represents:
• a phenyl optionally substituted with one or more Y1, or
• a 5- or 6-membered heteroaryl optionally substituted with one or more Y2;
• each Y1 independently represents halo, Ra1, —CN, —N3, —N(Rb1)Rc1 or —ORd1;
• each Y2 independently represents halo, Ra2, —CN, —N3, —N(Rb2)Rc2 or —ORd2;
• ring A represents 4- to 7-membered cycloalkyl or 4- to 7-membered heterocycloalkyl comprising one or two heteroatoms selected from N or O;
• n represents 0 to 5;
• when present on a carbon atom, each Z independently represents halo, Ra3, —CN, —N3, —N(Rb3)Rc3, —ORd3, —S(O)pRe3, —S(O)qN(Rf3)Rg3, —N(Rh3)S(O)tRi3, or ═O;
• when present on a nitrogen atom, each Z independently represents Ra3, —S(O)pRe3, or —S(O)qN(Rf3)Rg3;
• each Ra1 and Ra2 independently represents C1-6 alkyl optionally substituted by one or more halo;
• each Ra1 and Ra2 independently represents C1-6 alkyl optionally substituted by one or more halo;
• each Ra3, Re3, and Ri3 independently represents C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl each optionally substituted by one or more groups independently selected from halo and G1;
• each Rb1, Rb2, Rb3, Rc1, Rc2, Rc3, Rd1, Rd2, Rd3, Rf3, Rg3 and Rh3 independently represents H, or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl each optionally substituted by one or more groups independently selected from halo and G2;
• or alternatively any of Rb3 and Rc3, and/or Rf3 and Rg3 may be linked together to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from halo, C1-3 alkyl optionally substituted by one or more halo, and ═O;
• each G1 and G2 independently represents Ra4, —CN, —N3, —N(Rb4)Rc4, —ORd4, —S(O)pRe4, —S(O)qN(Rf4)Rg4, —N(Rh4)S(O)rRi4 or ═O;
• each Ra4 independently represents phenyl or 5- or 6-membered heteroaryl, each optionally substituted by one or more group selected from halo, Ra5, —CN, —N3, —N(Rb5)Rc5, —ORd5, μS(O)pRe5, —S(O)qN(Rf5)Rg5, or —N(Rh5)S(O)tRi5;
• each Rb4, Rc4, Rd4, Rf4, Rh4 and Rg4 independently represents H, or C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl optionally substituted by one or more halo, —CN or ═O;
• each Re4 and Ri4 independently represents C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl each optionally substituted by one or more halo or —CN;
• or alternatively any of Rb4 and Rc4 and/or Rf4 and Rg4 may be linked together to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from halo, C1-3 alkyl optionally substituted by one or more halo, and ═O;
• each Ra5, Re5, and Ri5 independently represents C1-6 alkyl, C2-6 alkenyl, or C2-6 alkynyl each optionally substituted by one or more groups independently selected from from halo, C1-3 alkyl optionally substituted by one or more halo, and ═O;
• each Rb5, Rc5, Rd5, Rf5, Rg5 and Rh5 independently represents H, or C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl each optionally substituted by one or more groups independently selected from halo, C1-3 alkyl optionally substituted by one or more halo, and ═O;
• or alternatively any of Rb5 and Rc5, and/or Rf5 and Rg5 may be linked together to form, together with the nitrogen atom to which they are attached, a 4- to 6-membered ring, which ring optionally contains one further heteroatom and which ring optionally is substituted by one or more groups independently selected from halo, C1-3 alkyl optionally substituted by one or more halo, and ═O;
• each p independently represents 0, 1 or 2;
• each q independently represents 1 or 2;
• each r independently represents 1 or 2;
• and
• each t independently represents 1 or 2,
• with the provisos (A) to (C) that the compound of formula I is not any of the following:
• (A)
• 4-[[2-(4-amino-3,5-dichlorophenyl)-2-hydroxyethyl]amino]cyclohexan-1-ol;
• (B)
• (αR)-α-[[(3-Methylcyclobutyl)amino]methyl]benzenemethanol;
• (αS)-α-[[(3-Methylcyclobutyl)amino]methyl]benzenemethanol;
• α-[[(3-Methylcyclobutyl)amino]methyl]benzenemethanol;
• α-[[(3-Aminocyclobutyl)amino]methyl]benzenemethanol;
• (αR)-α-[[(3-Hydroxycyclobutyl)amino]methyl]benzenemethanol;
• (αS)-α-[[(3-Hydroxycyclobutyl)amino]methyl]benzenemethanol;
• α-[[(3-Hydroxycyclobutyl)amino]methyl]benzenemethanol;
• α-[[(3-Methylcyclobutyl)amino]methyl]-3-pyridinemethanol;
• α-[[(3-Methylcyclobutyl)amino]methyl]-4-pyridinemethanol;
• α-[[(4-Methylcyclohexyl)amino]methyl]benzenemethanol;
• (αS)-α-[[(3-Methylcyclopentyl)amino]methyl]benzenemethanol;
• (αR)-α-[[(3-Methylcyclopentyl)amino]methyl]benzenemethanol;
• α-[[(trans-4-Methylcyclohexyl)amino]methyl]benzenemethanol;
• α-[[(3-Aminocyclopentyl)amino]methyl]benzenemethanol;
• α-[[(3-Methylcyclopentyl)amino]methyl]benzenemethanol;
• α-[[(3-Methylcyclohexyl)amino]methyl]benzenemethanol;
• α-[[(3-Aminocyclohexyl)amino]methyl]benzenemethanol;
• α-[[(4-Aminocyclohexyl)amino]methyl]benzenemethanol;
• α-[[(3-Fluorocyclobutyl)amino]methyl]benzenemethanol;
• α-[[(3-Methylcyclobutyl)amino]methyl]-2-pyridinemethanol;
• α-[[(3-Hydroxycyclobutyl)amino]methyl]-3-pyridinemethanol;
• (αR)-α-[[(3-Fluorocyclobutyl)amino]methyl]benzenemethanol;
• α-[[(4-Methylcycloheptyl)amino]methyl]benzenemethanol;
• (αR)-α-[[(1-Methyl-3-azetidinyl)amino]methyl]benzenemethanol;
• α-[[(1-Methyl-3-azetidinyl)amino]methyl]benzenemethanol;
• (αS)-α-[[(1-Methyl-3-azetidinyl)amino]methyl]benzenemethanol;
• α-[[(4-Hydroxycyclohexyl)amino]methyl]benzenemethanol;
• α-[[(3-Methylcyclopentyl)amino]methyl]-3-pyridinemethanol;
• α-[[(3-Methylcyclopentyl)amino]methyl]-4-pyridinemethanol;
• α-[[(3-Hydroxycyclobutyl)amino]methyl]-2-pyridinemethanol;
• α-[[(4-Methylcyclohexyl)amino]methyl]-4-pyridinemethanol;
• α-[[(3-Methylcyclohexyl)amino]methyl]-4-pyridinemethanol;
• (αR)-α-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]benzenemethanol;
• (αS)-α-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]benzenemethanol;
• α-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]benzenemethanol;
• 5-[(2-Hydroxy-2-phenylethyl)amino]cyclooctanol;
• α-[[(3-Fluorocyclobutyl)amino]methyl]-3-pyridinemethanol;
• α-[[(1-Methyl-3-piperidinyl)amino]methyl]benzenemethanol;
• α-[[(1-Methyl-3-azetidinyl)amino]methyl]-3-pyridinemethanol;
• α-[[(Hexahydro-1-methyl-1H-azepin-4-yl)amino]methyl]benzenemethanol;
• α-[[(3-Fluorocyclobutyl)amino]methyl]-2-pyridinemethanol;
• α-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]-4-pyridinemethanol;
• α-[[(1-Methyl-3-pyrrolidinyl)amino]methyl]-3-pyridinemethanol;
• α-[[(1-methyl-4-piperidinyl)amino]methyl]-benzenemethanol hydrochloride;
• α-[[(1-Methyl-3-azetidinyl)amino]methyl]-2-pyridinemethanol;
• (C)
• α-[[(1-Methyl-4-piperidinyl)amino]methyl]benzenemethanol,
• 2-((1-benzylpiperidin-4-yl)amino)-1-phenylethanol,
• 4-(1-hydroxy-2-((1-methylpiperidin-4-yl)amino)ethyl)phenol,
• 4-(2-((1-benzylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,
• 4-(2-((1-butylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,
• 3-(2-((1-butylpiperidin-4-yl)amino)-1-hydroxyethyl)phenol,
• 4-(1-hydroxy-2-((1-(2-methoxyethyl)piperidin-4-yl)amino)ethyl)phenol, or
• 4-(1-hydroxy-2-((1-phenethylpiperidin-4-yl)amino)ethyl)phenol.