JP2013523618A5 - - Google Patents

Info

Publication number

JP2013523618A5

JP2013523618A5 JP2013500534A JP2013500534A JP2013523618A5 JP 2013523618 A5 JP2013523618 A5 JP 2013523618A5 JP 2013500534 A JP2013500534 A JP 2013500534A JP 2013500534 A JP2013500534 A JP 2013500534A JP 2013523618 A5 JP2013523618 A5 JP 2013523618A5

Authority

JP

Japan

Prior art keywords

lys

ethoxy

amino

acetyl

leu

Prior art date

2011-03-28

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.)

Granted

Links

• Espacenet
• Global Dossier
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• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 55
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 44
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 26
• 108060003199 Glucagon Proteins 0.000 claims 25
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 22
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 22
• -1 18-hydroxy-18-oxooctadecanoyl Chemical group 0.000 claims 14
• 229960004666 glucagon Drugs 0.000 claims 12
• 229910052757 nitrogen Inorganic materials 0.000 claims 12
• 208000013016 Hypoglycemia Diseases 0.000 claims 10
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 9
• 150000001413 amino acids Chemical group 0.000 claims 8
• 230000002218 hypoglycaemic effect Effects 0.000 claims 8
• 125000001424 substituent group Chemical group 0.000 claims 7
• 229910052799 carbon Inorganic materials 0.000 claims 6
• 239000008194 pharmaceutical composition Substances 0.000 claims 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 5
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 5
• 208000002705 Glucose Intolerance Diseases 0.000 claims 4
• 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 claims 4
• 201000009104 prediabetes syndrome Diseases 0.000 claims 4
• 102000051325 Glucagon Human genes 0.000 claims 3
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims 3
• 208000008589 Obesity Diseases 0.000 claims 3
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims 3
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims 3
• 206010012601 diabetes mellitus Diseases 0.000 claims 3
• 239000003814 drug Substances 0.000 claims 3
• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Substances N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims 3
• 235000020824 obesity Nutrition 0.000 claims 3
• 229960003104 ornithine Drugs 0.000 claims 3
• 208000032841 Bulimia Diseases 0.000 claims 2
• 102000004877 Insulin Human genes 0.000 claims 2
• 108090001061 Insulin Proteins 0.000 claims 2
• 239000004472 Lysine Substances 0.000 claims 2
• 206010033307 Overweight Diseases 0.000 claims 2
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 2
• 150000001875 compounds Chemical group 0.000 claims 2
• 210000001035 gastrointestinal tract Anatomy 0.000 claims 2
• 229940125396 insulin Drugs 0.000 claims 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
• 238000006467 substitution reaction Methods 0.000 claims 2
• 229910052717 sulfur Inorganic materials 0.000 claims 2
• 239000011593 sulfur Substances 0.000 claims 2
• WFWVBGKINIRMTD-FHODTQPZSA-N 18-[[(1S)-1-carboxy-4-[2-[2-[2-[2-[2-[(7S)-3,7-diamino-7-carboxy-2-oxoheptoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-4-oxobutyl]amino]-18-oxooctadecanoic acid Chemical compound OC(=O)[C@@H](N)CCCC(N)C(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](C(O)=O)NC(=O)CCCCCCCCCCCCCCCCC(O)=O WFWVBGKINIRMTD-FHODTQPZSA-N 0.000 claims 1
• 201000001320 Atherosclerosis Diseases 0.000 claims 1
• 206010004716 Binge eating Diseases 0.000 claims 1
• 206010006550 Bulimia nervosa Diseases 0.000 claims 1
• MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 claims 1
• 206010061818 Disease progression Diseases 0.000 claims 1
• 208000032928 Dyslipidaemia Diseases 0.000 claims 1
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 1
• 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 1
• 208000032003 Glycogen storage disease due to glucose-6-phosphatase deficiency Diseases 0.000 claims 1
• 206010018464 Glycogen storage disease type I Diseases 0.000 claims 1
• 206010019708 Hepatic steatosis Diseases 0.000 claims 1
• 206010020772 Hypertension Diseases 0.000 claims 1
• 208000017170 Lipid metabolism disease Diseases 0.000 claims 1
• 102100040918 Pro-glucagon Human genes 0.000 claims 1
• 108010039491 Ricin Proteins 0.000 claims 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 1
• 239000002253 acid Substances 0.000 claims 1
• 150000007513 acids Chemical class 0.000 claims 1
• 150000001408 amides Chemical class 0.000 claims 1
• 230000036528 appetite Effects 0.000 claims 1
• 235000019789 appetite Nutrition 0.000 claims 1
• 125000004429 atom Chemical group 0.000 claims 1
• 239000002876 beta blocker Substances 0.000 claims 1
• 208000014679 binge eating disease Diseases 0.000 claims 1
• 230000037396 body weight Effects 0.000 claims 1
• 150000001721 carbon Chemical group 0.000 claims 1
• 208000029078 coronary artery disease Diseases 0.000 claims 1
• 201000010099 disease Diseases 0.000 claims 1
• 230000005750 disease progression Effects 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
• 229940079593 drug Drugs 0.000 claims 1
• 206010013663 drug dependence Diseases 0.000 claims 1
• 230000037406 food intake Effects 0.000 claims 1
• 235000012631 food intake Nutrition 0.000 claims 1
• 230000002496 gastric effect Effects 0.000 claims 1
• 201000004541 glycogen storage disease I Diseases 0.000 claims 1
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
• 201000001421 hyperglycemia Diseases 0.000 claims 1
• 230000006698 induction Effects 0.000 claims 1
• 230000005764 inhibitory process Effects 0.000 claims 1
• 206010022498 insulinoma Diseases 0.000 claims 1
• 238000000034 method Methods 0.000 claims 1
• 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
• 230000004899 motility Effects 0.000 claims 1
• 208000021255 pancreatic insulinoma Diseases 0.000 claims 1
• 238000007911 parenteral administration Methods 0.000 claims 1
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
• 230000035935 pregnancy Effects 0.000 claims 1
• 229940002612 prodrug Drugs 0.000 claims 1
• 239000000651 prodrug Substances 0.000 claims 1
• 150000003839 salts Chemical class 0.000 claims 1
• 230000036186 satiety Effects 0.000 claims 1
• 235000019627 satiety Nutrition 0.000 claims 1
• 239000000126 substance Substances 0.000 claims 1
• 208000011117 substance-related disease Diseases 0.000 claims 1
• 230000001225 therapeutic effect Effects 0.000 claims 1
• 230000004584 weight gain Effects 0.000 claims 1
• 235000019786 weight gain Nutrition 0.000 claims 1
• 230000004580 weight loss Effects 0.000 claims 1
• RYBACDXXFOTADK-NFJMKROFSA-N CC([C@@H](C(O)=O)NN)O Chemical compound CC([C@@H](C(O)=O)NN)O RYBACDXXFOTADK-NFJMKROFSA-N 0.000 description 1
• 0 CC*(C)C[C@](CCCCNC([C@](CCCCNC(COCCOCCNC(CC[C@](NC(CCCCCCCCCCCCCCCCC(O)=O)=O)I(O)=O)=O)=O)N)=O)(C=O)NC Chemical compound CC*(C)C[C@](CCCCNC([C@](CCCCNC(COCCOCCNC(CC[C@](NC(CCCCCCCCCCCCCCCCC(O)=O)=O)I(O)=O)=O)=O)N)=O)(C=O)NC 0.000 description 1
• IZSDKPOQGKLOJM-HEVIKAOCSA-N NN[C@@H](CCCCNC(COCCOCCNC(COCCOCCNC(CC[C@@H](C(O)=O)NC(CCCCCCCCCCCCCCCCC(O)=O)=O)=O)=O)=O)C(O)=O Chemical compound NN[C@@H](CCCCNC(COCCOCCNC(COCCOCCNC(CC[C@@H](C(O)=O)NC(CCCCCCCCCCCCCCCCC(O)=O)=O)=O)=O)=O)C(O)=O IZSDKPOQGKLOJM-HEVIKAOCSA-N 0.000 description 1