CA2629348C - Glucagon receptor antagonists, preparation and therapeutic uses - Google Patents

Info

Publication number

CA2629348C

CA2629348C CA2629348A CA2629348A CA2629348C CA 2629348 C CA2629348 C CA 2629348C CA 2629348 A CA2629348 A CA 2629348A CA 2629348 A CA2629348 A CA 2629348A CA 2629348 C CA2629348 C CA 2629348C

Authority

CA

Canada

Prior art keywords

halogens

optionally substituted

butyl

methyl

compound

Prior art date

2005-11-17

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.)

Expired - Fee Related

Links

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• Global Dossier
• CIPO
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• 229940122904 Glucagon receptor antagonist Drugs 0.000 title abstract description 9
• 238000002360 preparation method Methods 0.000 title description 43
• 230000001225 therapeutic effect Effects 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 167
• 150000003839 salts Chemical class 0.000 claims abstract description 30
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 19
• 229910052736 halogen Inorganic materials 0.000 claims description 96
• 150000002367 halogens Chemical class 0.000 claims description 68
• -1 3,3-dimethylbutyl Chemical group 0.000 claims description 38
• 238000011282 treatment Methods 0.000 claims description 27
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
• 239000001257 hydrogen Substances 0.000 claims description 13
• 229910052739 hydrogen Inorganic materials 0.000 claims description 13
• 239000003814 drug Substances 0.000 claims description 12
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 11
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 11
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 125000003342 alkenyl group Chemical group 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
• 239000003937 drug carrier Substances 0.000 claims description 8
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
• 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 7
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
• 150000002431 hydrogen Chemical class 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 claims description 5
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
• 125000000439 4-methylpentoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 claims description 2
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 claims description 2
• 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• JLDJSIOVMRCTAX-UHFFFAOYSA-N 3-[[4-[1-[4-(4-cyanophenyl)anilino]-3-methylbutyl]benzoyl]amino]propanoic acid Chemical compound C=1C=C(C(=O)NCCC(O)=O)C=CC=1C(CC(C)C)NC(C=C1)=CC=C1C1=CC=C(C#N)C=C1 JLDJSIOVMRCTAX-UHFFFAOYSA-N 0.000 claims 3
• BGJGBFZVODHBGF-UHFFFAOYSA-N 3-[[4-[1-[4-(4-tert-butylphenyl)anilino]-3-methylbutyl]benzoyl]amino]propanoic acid Chemical compound C=1C=C(C(=O)NCCC(O)=O)C=CC=1C(CC(C)C)NC(C=C1)=CC=C1C1=CC=C(C(C)(C)C)C=C1 BGJGBFZVODHBGF-UHFFFAOYSA-N 0.000 claims 3
• UQPIEHMOLHNOQO-UHFFFAOYSA-N 3-[[4-[1-(3-methoxy-4-phenylanilino)hexyl]benzoyl]amino]propanoic acid Chemical compound C=1C=C(C(=O)NCCC(O)=O)C=CC=1C(CCCCC)NC(C=C1OC)=CC=C1C1=CC=CC=C1 UQPIEHMOLHNOQO-UHFFFAOYSA-N 0.000 claims 1
• HDOXXWVGJGIWNK-UHFFFAOYSA-N 3-[[4-[1-[3,5-dimethyl-4-[4-(trifluoromethyl)phenyl]anilino]-3-methylbutyl]benzoyl]amino]propanoic acid Chemical compound C=1C=C(C(=O)NCCC(O)=O)C=CC=1C(CC(C)C)NC(C=C1C)=CC(C)=C1C1=CC=C(C(F)(F)F)C=C1 HDOXXWVGJGIWNK-UHFFFAOYSA-N 0.000 claims 1
• LXYGMSILKVAJIL-UHFFFAOYSA-N 3-[[4-[1-[4-(4-cyanophenyl)anilino]hexyl]benzoyl]amino]propanoic acid Chemical compound C=1C=C(C(=O)NCCC(O)=O)C=CC=1C(CCCCC)NC(C=C1)=CC=C1C1=CC=C(C#N)C=C1 LXYGMSILKVAJIL-UHFFFAOYSA-N 0.000 claims 1
• RSTCYOJNAFOPJU-UHFFFAOYSA-N 3-[[4-[3-methyl-1-[4-[4-(trifluoromethyl)phenyl]anilino]butyl]benzoyl]amino]propanoic acid Chemical compound C=1C=C(C(=O)NCCC(O)=O)C=CC=1C(CC(C)C)NC(C=C1)=CC=C1C1=CC=C(C(F)(F)F)C=C1 RSTCYOJNAFOPJU-UHFFFAOYSA-N 0.000 claims 1
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
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• 102000051325 Glucagon Human genes 0.000 abstract description 62
• 108060003199 Glucagon Proteins 0.000 abstract description 62
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• 238000000034 method Methods 0.000 abstract description 39
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