TWI852944B - 生長抑制素(somatostatin)調節劑及其用途 - Google Patents

Info

Publication number

TWI852944B

TWI852944B TW108133468A TW108133468A TWI852944B TW I852944 B TWI852944 B TW I852944B TW 108133468 A TW108133468 A TW 108133468A TW 108133468 A TW108133468 A TW 108133468A TW I852944 B TWI852944 B TW I852944B

Authority

TW

Taiwan

Prior art keywords

substituted

unsubstituted

alkyl

hydrogen

fluoro

Prior art date

2018-09-18

Links

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• Global Dossier
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• 108010056088 Somatostatin Proteins 0.000 title abstract description 20
• 102000005157 Somatostatin Human genes 0.000 title abstract description 19
• NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 title abstract description 19
• 229960000553 somatostatin Drugs 0.000 title abstract description 19
• 150000001875 compounds Chemical class 0.000 claims abstract description 283
• 239000003814 drug Substances 0.000 claims abstract description 34
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 28
• 229910052739 hydrogen Inorganic materials 0.000 claims description 193
• 239000001257 hydrogen Substances 0.000 claims description 193
• 239000000203 mixture Substances 0.000 claims description 116
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 94
• -1 -CH2CH2OH Chemical group 0.000 claims description 85
• 150000002431 hydrogen Chemical group 0.000 claims description 84
• 150000003839 salts Chemical class 0.000 claims description 84
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 72
• 125000000217 alkyl group Chemical group 0.000 claims description 71
• 229910052736 halogen Inorganic materials 0.000 claims description 47
• 150000002367 halogens Chemical group 0.000 claims description 47
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 46
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 40
• 241000124008 Mammalia Species 0.000 claims description 38
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
• 229940079593 drug Drugs 0.000 claims description 15
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 15
• 108010051696 Growth Hormone Proteins 0.000 claims description 14
• 102100038803 Somatotropin Human genes 0.000 claims description 14
• 239000000122 growth hormone Substances 0.000 claims description 14
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 12
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 9
• 229940088597 hormone Drugs 0.000 claims description 9
• 239000005556 hormone Substances 0.000 claims description 9
• 230000028327 secretion Effects 0.000 claims description 9
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 8
• GWXXLUISNRRCDH-UHFFFAOYSA-N 2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-fluoro-5-methylphenyl)pyridin-3-yl]-7-methoxy-3H-benzimidazole-5-carbonitrile Chemical compound NC1=NC=C(C(=C1C1=NC2=C(N1)C=C(C=C2OC)C#N)N1CCC(CC1)N)C1=CC(=CC(=C1)C)F GWXXLUISNRRCDH-UHFFFAOYSA-N 0.000 claims description 7
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 claims description 7
• 206010000599 Acromegaly Diseases 0.000 claims description 7
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• NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound 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 description 6
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• 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 description 4
• 229960004666 glucagon Drugs 0.000 claims description 4
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• 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
• MNTYWCOOZNFBOW-UHFFFAOYSA-N 2-[4-(4-aminopiperidin-1-yl)-2-(dimethylamino)-5-(3-fluoro-5-methylphenyl)pyridin-3-yl]-7-methoxy-3H-benzimidazole-5-carbonitrile Chemical compound NC1CCN(CC1)C1=C(C(=NC=C1C1=CC(=CC(=C1)C)F)N(C)C)C1=NC2=C(N1)C=C(C=C2OC)C#N MNTYWCOOZNFBOW-UHFFFAOYSA-N 0.000 claims description 3
• LIEKIPDHLZCKJD-UHFFFAOYSA-N 4-(4-aminopiperidin-1-yl)-3-(6-fluoro-4-methoxy-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridine-2-carbonitrile Chemical compound NC1CCN(CC1)C1=C(C(=NC=C1C1=CC(=CC(=C1)C)F)C#N)C1=NC2=C(N1)C=C(C=C2OC)F LIEKIPDHLZCKJD-UHFFFAOYSA-N 0.000 claims description 3
• NQPBTXCQNMNVLD-UHFFFAOYSA-N 4-(4-aminopiperidin-1-yl)-3-(6-fluoro-4-methoxy-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)pyridine-2-carboxamide Chemical compound NC1CCN(CC1)C1=C(C(=NC=C1C1=CC(=CC(=C1)C)F)C(=O)N)C1=NC2=C(N1)C=C(C=C2OC)F NQPBTXCQNMNVLD-UHFFFAOYSA-N 0.000 claims description 3
• 102000004877 Insulin Human genes 0.000 claims description 3
• 108090001061 Insulin Proteins 0.000 claims description 3
• 229940125396 insulin Drugs 0.000 claims description 3
• 235000003170 nutritional factors Nutrition 0.000 claims description 3
• XWCLWYVYMUTYNP-UHFFFAOYSA-N 2-[2-amino-4-(4-aminopiperidin-1-yl)-5-(3-chloro-5-fluorophenyl)pyridin-3-yl]-7-methoxy-3H-benzimidazole-5-carbonitrile Chemical compound NC1=NC=C(C(=C1C1=NC2=C(N1)C=C(C=C2OC)C#N)N1CCC(CC1)N)C1=CC(=CC(=C1)F)Cl XWCLWYVYMUTYNP-UHFFFAOYSA-N 0.000 claims description 2
• TXQQISIPFAYEPW-UHFFFAOYSA-N 4-(4-aminopiperidin-1-yl)-3-(6-fluoro-4-methoxy-1H-benzimidazol-2-yl)-5-(3-fluoro-5-methylphenyl)-N-methylpyridine-2-carboxamide Chemical compound NC1CCN(CC1)C1=C(C(=NC=C1C1=CC(=CC(=C1)C)F)C(=O)NC)C1=NC2=C(N1)C=C(C=C2OC)F TXQQISIPFAYEPW-UHFFFAOYSA-N 0.000 claims description 2
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• 108010057464 Prolactin Proteins 0.000 claims description 2
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