AU2014230215A1 - Acylaminocycloalkyl compounds suitable for treating disorders that respond to modulation of dopamine D3 receptor - Google Patents

Info

Publication number

AU2014230215A1

AU2014230215A1 AU2014230215A AU2014230215A AU2014230215A1 AU 2014230215 A1 AU2014230215 A1 AU 2014230215A1 AU 2014230215 A AU2014230215 A AU 2014230215A AU 2014230215 A AU2014230215 A AU 2014230215A AU 2014230215 A1 AU2014230215 A1 AU 2014230215A1

Authority

AU

Australia

Prior art keywords

trans

ethyl

butyl

tert

hydroxy

Prior art date

2013-03-15

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 316
• 108090000525 Dopamine D3 Receptors Proteins 0.000 title claims abstract description 32
• 102000004073 Dopamine D3 Receptors Human genes 0.000 title claims abstract description 32
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 77
• 150000003839 salts Chemical class 0.000 claims abstract description 49
• 150000001204 N-oxides Chemical class 0.000 claims abstract description 41
• -1 cyclic radical Chemical class 0.000 claims description 417
• 150000003254 radicals Chemical class 0.000 claims description 162
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 78
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 76
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 67
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 63
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 62
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 62
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 61
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 61
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 59
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 58
• 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 55
• 208000035475 disorder Diseases 0.000 claims description 51
• 238000000034 method Methods 0.000 claims description 47
• 239000000651 prodrug Substances 0.000 claims description 44
• 229940002612 prodrug Drugs 0.000 claims description 44
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 41
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 40
• 239000003814 drug Substances 0.000 claims description 34
• 229910052739 hydrogen Inorganic materials 0.000 claims description 33
• 238000011282 treatment Methods 0.000 claims description 33
• 239000001257 hydrogen Substances 0.000 claims description 32
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 29
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
• 125000000217 alkyl group Chemical group 0.000 claims description 26
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 25
• 229940079593 drug Drugs 0.000 claims description 24
• 239000000126 substance Substances 0.000 claims description 22
• 229910052799 carbon Inorganic materials 0.000 claims description 17
• 125000005475 oxolanyl group Chemical group 0.000 claims description 17
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
• 208000019901 Anxiety disease Diseases 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
• 201000000980 schizophrenia Diseases 0.000 claims description 14
• 208000012661 Dyskinesia Diseases 0.000 claims description 13
• 208000018737 Parkinson disease Diseases 0.000 claims description 13
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
• 125000003566 oxetanyl group Chemical group 0.000 claims description 13
• 229910052731 fluorine Inorganic materials 0.000 claims description 12
• 239000008194 pharmaceutical composition Substances 0.000 claims description 12
• 230000036506 anxiety Effects 0.000 claims description 11
• 208000010877 cognitive disease Diseases 0.000 claims description 11
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 10
• 239000011737 fluorine Substances 0.000 claims description 10
• 239000003446 ligand Substances 0.000 claims description 8
• 206010062237 Renal impairment Diseases 0.000 claims description 7
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
• 239000001301 oxygen Substances 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
• 208000020925 Bipolar disease Diseases 0.000 claims description 6
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 6
• WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 6
• WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 6
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 6
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 claims description 6
• 208000030814 Eating disease Diseases 0.000 claims description 5
• 208000019454 Feeding and Eating disease Diseases 0.000 claims description 5
• 208000002193 Pain Diseases 0.000 claims description 5
• 210000003169 central nervous system Anatomy 0.000 claims description 5
• 235000014632 disordered eating Nutrition 0.000 claims description 5
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
• 230000008450 motivation Effects 0.000 claims description 4
• 125000006420 1-fluorocyclopropyl group Chemical group [H]C1([H])C([H])([H])C1(F)* 0.000 claims description 3
• UCUHQXIAXJMZRI-UHFFFAOYSA-N 4-hydroxycyclohexane-1-carboxamide Chemical compound NC(=O)C1CCC(O)CC1 UCUHQXIAXJMZRI-UHFFFAOYSA-N 0.000 claims description 2
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• WOVNLPQSBXFSSV-NEBLVTBLSA-N CC(C)(C)C1=NC(CCOC)=CC(N2CCN(CC[C@@H]3CC[C@H](CC3)NC(=O)C3CC(O)(C3)C(F)(F)F)CC2)=N1 Chemical compound CC(C)(C)C1=NC(CCOC)=CC(N2CCN(CC[C@@H]3CC[C@H](CC3)NC(=O)C3CC(O)(C3)C(F)(F)F)CC2)=N1 WOVNLPQSBXFSSV-NEBLVTBLSA-N 0.000 claims description 2
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• ZKQGJMPEAJQJIT-GHYQBBAPSA-N N([C@@H]1CC[C@@H](CC1)CCN1CCN(CC1)C=1C=C(N=C(N=1)C(C)(C)C)C1CCC1)C(=O)[C@H]1CC[C@H](O)CC1 Chemical compound N([C@@H]1CC[C@@H](CC1)CCN1CCN(CC1)C=1C=C(N=C(N=1)C(C)(C)C)C1CCC1)C(=O)[C@H]1CC[C@H](O)CC1 ZKQGJMPEAJQJIT-GHYQBBAPSA-N 0.000 claims description 2
• UNBJBRUJGOJLIT-VGOHXSHPSA-N N([C@@H]1C[C@@H](C1)CCN1CCN(CC1)C=1C=C(N=C(N=1)C(C)(C)C)C1CCC1)C(=O)[C@H]1CC[C@H](O)CC1 Chemical compound N([C@@H]1C[C@@H](C1)CCN1CCN(CC1)C=1C=C(N=C(N=1)C(C)(C)C)C1CCC1)C(=O)[C@H]1CC[C@H](O)CC1 UNBJBRUJGOJLIT-VGOHXSHPSA-N 0.000 claims description 2
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• UDRZDLDHIYMICU-AQNOAHGYSA-N n-[4-[2-[(3r)-4-[2-tert-butyl-6-(2-methoxyethyl)pyrimidin-4-yl]-3-methylpiperazin-1-yl]ethyl]cyclohexyl]-4-hydroxycyclohexane-1-carboxamide Chemical compound CC(C)(C)C1=NC(CCOC)=CC(N2[C@@H](CN(CCC3CCC(CC3)NC(=O)C3CCC(O)CC3)CC2)C)=N1 UDRZDLDHIYMICU-AQNOAHGYSA-N 0.000 claims description 2
• ZKQGJMPEAJQJIT-UHFFFAOYSA-N n-[4-[2-[4-(2-tert-butyl-6-cyclobutylpyrimidin-4-yl)piperazin-1-yl]ethyl]cyclohexyl]-4-hydroxycyclohexane-1-carboxamide Chemical compound N=1C(C(C)(C)C)=NC(C2CCC2)=CC=1N(CC1)CCN1CCC(CC1)CCC1NC(=O)C1CCC(O)CC1 ZKQGJMPEAJQJIT-UHFFFAOYSA-N 0.000 claims description 2
• HFUDTZKQQFGRIB-UHFFFAOYSA-N n-[4-[2-[4-(2-tert-butyl-6-propan-2-ylpyrimidin-4-yl)piperazin-1-yl]ethyl]cyclohexyl]-4-hydroxycyclohexane-1-carboxamide Chemical compound CC(C)(C)C1=NC(C(C)C)=CC(N2CCN(CCC3CCC(CC3)NC(=O)C3CCC(O)CC3)CC2)=N1 HFUDTZKQQFGRIB-UHFFFAOYSA-N 0.000 claims description 2
• NXWBOAQGGZVKBT-UHFFFAOYSA-N cyclobutanecarboxamide Chemical compound NC(=O)C1C[CH]C1 NXWBOAQGGZVKBT-UHFFFAOYSA-N 0.000 claims 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 2
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