ES2391109T3 - Antagonistas del receptor de glucagón, preparación y usos terapéuticos - Google Patents

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Publication number

ES2391109T3

ES2391109T3 ES06850109T ES06850109T ES2391109T3 ES 2391109 T3 ES2391109 T3 ES 2391109T3 ES 06850109 T ES06850109 T ES 06850109T ES 06850109 T ES06850109 T ES 06850109T ES 2391109 T3 ES2391109 T3 ES 2391109T3

Authority

ES

Spain

Prior art keywords

alkyl

halogens

optionally substituted

butyl

independently

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.)

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• 238000002360 preparation method Methods 0.000 title description 41
• 229940122904 Glucagon receptor antagonist Drugs 0.000 title description 9
• 230000001225 therapeutic effect Effects 0.000 title description 5
• 150000001875 compounds Chemical class 0.000 claims abstract description 159
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 84
• 150000002367 halogens Chemical class 0.000 claims abstract description 68
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 27
• 150000003839 salts Chemical class 0.000 claims abstract description 26
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 5
• -1 3,3-dimethylbutyl Chemical group 0.000 claims description 37
• 238000011282 treatment Methods 0.000 claims description 34
• 206010012601 diabetes mellitus Diseases 0.000 claims description 22
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims description 17
• 239000003814 drug Substances 0.000 claims description 11
• 229910052739 hydrogen Inorganic materials 0.000 claims description 11
• 239000001257 hydrogen Substances 0.000 claims description 11
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 11
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 229910052731 fluorine Inorganic materials 0.000 claims description 10
• 239000011737 fluorine Substances 0.000 claims description 10
• 208000008589 Obesity Diseases 0.000 claims description 9
• 201000001421 hyperglycemia Diseases 0.000 claims description 9
• 235000020824 obesity Nutrition 0.000 claims description 9
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 9
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 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
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 239000003937 drug carrier Substances 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
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
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• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 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
• 230000007823 neuropathy Effects 0.000 claims description 5
• 230000029663 wound healing Effects 0.000 claims description 5
• 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 description 4
• 208000033463 Ischaemic neuropathy Diseases 0.000 claims description 4
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• 208000031225 myocardial ischemia Diseases 0.000 claims description 4
• 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 4
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
• 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 description 3
• 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 description 3
• 150000002431 hydrogen Chemical class 0.000 claims description 3
• 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 3
• 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 description 2
• 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
• 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 2
• BIZGMTWBKDPTLH-UHFFFAOYSA-N propan-2-yl hypochlorite Chemical compound CC(C)OCl BIZGMTWBKDPTLH-UHFFFAOYSA-N 0.000 claims description 2
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
• 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
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 1
• 239000004305 biphenyl Substances 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract description 2
• 125000003545 alkoxy group Chemical group 0.000 abstract description 2
• 229960004666 glucagon Drugs 0.000 description 66
• 102000051325 Glucagon Human genes 0.000 description 62
• 108060003199 Glucagon Proteins 0.000 description 62
• MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 62
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