JP2023011007A5 - - Google Patents

Info

Publication number

JP2023011007A5

JP2023011007A5 JP2022188185A JP2022188185A JP2023011007A5 JP 2023011007 A5 JP2023011007 A5 JP 2023011007A5 JP 2022188185 A JP2022188185 A JP 2022188185A JP 2022188185 A JP2022188185 A JP 2022188185A JP 2023011007 A5 JP2023011007 A5 JP 2023011007A5

Authority

JP

Japan

Prior art keywords

methyl

dpp

inhibitor

butyn

xanthine

Prior art date

2022-11-25

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.)

Pending

Links

• Espacenet
• Global Dossier
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• 239000003814 drug Substances 0.000 claims 28
• 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 claims 23
• -1 ([1,5]naphthyridin-2-yl)methyl Chemical group 0.000 claims 12
• 206010062237 Renal impairment Diseases 0.000 claims 11
• 239000003795 chemical substances by application Substances 0.000 claims 11
• 239000013543 active substance Substances 0.000 claims 8
• 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 8
• 230000002265 prevention Effects 0.000 claims 8
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 8
• XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims 7
• 229960003105 metformin Drugs 0.000 claims 7
• LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical group N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 claims 5
• 208000001647 Renal Insufficiency Diseases 0.000 claims 5
• 229940079593 drug Drugs 0.000 claims 5
• 208000017169 kidney disease Diseases 0.000 claims 5
• 201000006370 kidney failure Diseases 0.000 claims 5
• HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 claims 4
• 102000004877 Insulin Human genes 0.000 claims 3
• 108090001061 Insulin Proteins 0.000 claims 3
• 239000008280 blood Substances 0.000 claims 3
• 210000004369 blood Anatomy 0.000 claims 3
• 230000008030 elimination Effects 0.000 claims 3
• 238000003379 elimination reaction Methods 0.000 claims 3
• 229940125396 insulin Drugs 0.000 claims 3
• 208000030159 metabolic disease Diseases 0.000 claims 3
• 239000002207 metabolite Substances 0.000 claims 3
• LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims 2
• DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](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(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims 2
• 229940100389 Sulfonylurea Drugs 0.000 claims 2
• 230000001154 acute effect Effects 0.000 claims 2
• 208000020832 chronic kidney disease Diseases 0.000 claims 2
• 230000000694 effects Effects 0.000 claims 2
• 208000028208 end stage renal disease Diseases 0.000 claims 2
• 201000000523 end stage renal failure Diseases 0.000 claims 2
• 230000029142 excretion Effects 0.000 claims 2
• 230000002496 gastric effect Effects 0.000 claims 2
• 210000003734 kidney Anatomy 0.000 claims 2
• 230000003907 kidney function Effects 0.000 claims 2
• 210000004185 liver Anatomy 0.000 claims 2
• 229960005095 pioglitazone Drugs 0.000 claims 2
• 150000003839 salts Chemical class 0.000 claims 2
• 230000001225 therapeutic effect Effects 0.000 claims 2
• 238000002560 therapeutic procedure Methods 0.000 claims 2
• HAKJUVBTRWXTRU-QGZVFWFLSA-N 2-[(3r)-3-aminopiperidin-1-yl]-3-but-2-ynyl-5-[(4-methylquinazolin-2-yl)methyl]imidazo[4,5-d]pyridazin-4-one Chemical compound N=1C=2C=NN(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 HAKJUVBTRWXTRU-QGZVFWFLSA-N 0.000 claims 1
• ZOTODWFVYUPZFO-GOSISDBHSA-N 2-[[8-[(3r)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-2,6-dioxopurin-1-yl]methyl]benzonitrile Chemical compound O=C1C=2N(CC#CC)C(N3C[C@H](N)CCC3)=NC=2N(C)C(=O)N1CC1=CC=CC=C1C#N ZOTODWFVYUPZFO-GOSISDBHSA-N 0.000 claims 1
• ISVBJQYIQQKSGK-MRXNPFEDSA-N 2-[[8-[(3r)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-2,6-dioxopurin-1-yl]methyl]pyridine-3-carbonitrile Chemical compound O=C1C=2N(CC#CC)C(N3C[C@H](N)CCC3)=NC=2N(C)C(=O)N1CC1=NC=CC=C1C#N ISVBJQYIQQKSGK-MRXNPFEDSA-N 0.000 claims 1
• HDARIOSGMVVPLE-LJQANCHMSA-N 2-[[8-[(3r)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-2,6-dioxopurin-1-yl]methyl]quinoline-3-carbonitrile Chemical compound N=1C=2N(C)C(=O)N(CC=3C(=CC4=CC=CC=C4N=3)C#N)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 HDARIOSGMVVPLE-LJQANCHMSA-N 0.000 claims 1
• BNPBEDWUQOSRHB-UHFFFAOYSA-N 8-[(2-amino-2-methylpropyl)-methylamino]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione Chemical compound C1=CC=CC2=NC(CN3C(=O)N(C)C=4N=C(N(C=4C3=O)CC#CC)N(C)CC(C)(C)N)=NC(C)=C21 BNPBEDWUQOSRHB-UHFFFAOYSA-N 0.000 claims 1
• ONMDRNPIEXAJEZ-MRXNPFEDSA-N 8-[(3r)-3-aminopiperidin-1-yl]-7-but-2-ynyl-1-[(4,6-dimethylpyrimidin-2-yl)methyl]-3-methylpurine-2,6-dione Chemical compound O=C1C=2N(CC#CC)C(N3C[C@H](N)CCC3)=NC=2N(C)C(=O)N1CC1=NC(C)=CC(C)=N1 ONMDRNPIEXAJEZ-MRXNPFEDSA-N 0.000 claims 1
• TTYUNRVFZJWXHB-MRXNPFEDSA-N 8-[(3r)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-(1,5-naphthyridin-2-ylmethyl)purine-2,6-dione Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=NC4=CC=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 TTYUNRVFZJWXHB-MRXNPFEDSA-N 0.000 claims 1
• ILTRPILDWNCOMQ-QGZVFWFLSA-N 8-[(3r)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-(quinazolin-2-ylmethyl)purine-2,6-dione Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=CN=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 ILTRPILDWNCOMQ-QGZVFWFLSA-N 0.000 claims 1
• GFMVACPPQCXLGW-QGZVFWFLSA-N 8-[(3r)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-(quinoxalin-6-ylmethyl)purine-2,6-dione Chemical compound N=1C=2N(C)C(=O)N(CC=3C=C4N=CC=NC4=CC=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 GFMVACPPQCXLGW-QGZVFWFLSA-N 0.000 claims 1
• YLTXBUGZVMPESA-OAHLLOKOSA-N 8-[(3r)-3-aminopiperidin-1-yl]-7-but-2-ynyl-3-methyl-1-[(4-methylpyrimidin-2-yl)methyl]purine-2,6-dione Chemical compound O=C1C=2N(CC#CC)C(N3C[C@H](N)CCC3)=NC=2N(C)C(=O)N1CC1=NC=CC(C)=N1 YLTXBUGZVMPESA-OAHLLOKOSA-N 0.000 claims 1
• OWVQLTBTGFYAHU-HNNXBMFYSA-N 8-[[(2s)-2-aminopropyl]-methylamino]-7-but-2-ynyl-3-methyl-1-[(4-methylquinazolin-2-yl)methyl]purine-2,6-dione Chemical compound C1=CC=CC2=NC(CN3C(=O)N(C)C=4N=C(N(C=4C3=O)CC#CC)N(C)C[C@H](C)N)=NC(C)=C21 OWVQLTBTGFYAHU-HNNXBMFYSA-N 0.000 claims 1
• 208000010444 Acidosis Diseases 0.000 claims 1
• 201000001320 Atherosclerosis Diseases 0.000 claims 1
• 206010007559 Cardiac failure congestive Diseases 0.000 claims 1
• 208000005156 Dehydration Diseases 0.000 claims 1
• 206010012735 Diarrhoea Diseases 0.000 claims 1
• 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 claims 1
• 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 claims 1
• 206010017605 Galactose intolerance Diseases 0.000 claims 1
• 208000027472 Galactosemias Diseases 0.000 claims 1
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 claims 1
• 206010019280 Heart failures Diseases 0.000 claims 1
• 102100024295 Maltase-glucoamylase Human genes 0.000 claims 1
• 206010027417 Metabolic acidosis Diseases 0.000 claims 1
• 206010028813 Nausea Diseases 0.000 claims 1
• 208000008589 Obesity Diseases 0.000 claims 1
• 229940123464 Thiazolidinedione Drugs 0.000 claims 1
• 206010047700 Vomiting Diseases 0.000 claims 1
• 206010000059 abdominal discomfort Diseases 0.000 claims 1
• 108010028144 alpha-Glucosidases Proteins 0.000 claims 1
• 230000003178 anti-diabetic effect Effects 0.000 claims 1
• 239000003472 antidiabetic agent Substances 0.000 claims 1
• 210000000941 bile Anatomy 0.000 claims 1
• 230000036772 blood pressure Effects 0.000 claims 1
• 230000001684 chronic effect Effects 0.000 claims 1
• 230000018044 dehydration Effects 0.000 claims 1
• 238000006297 dehydration reaction Methods 0.000 claims 1
• 206010012601 diabetes mellitus Diseases 0.000 claims 1
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 1
• 230000024924 glomerular filtration Effects 0.000 claims 1
• 230000010224 hepatic metabolism Effects 0.000 claims 1
• 230000000968 intestinal effect Effects 0.000 claims 1
• 150000002632 lipids Chemical class 0.000 claims 1
• 230000002503 metabolic effect Effects 0.000 claims 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• 230000008693 nausea Effects 0.000 claims 1
• 125000006504 o-cyanobenzyl group Chemical group [H]C1=C([H])C(C#N)=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
• 235000020824 obesity Nutrition 0.000 claims 1
• 230000037361 pathway Effects 0.000 claims 1
• 229960002354 repaglinide Drugs 0.000 claims 1
• YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims 1
• 150000001467 thiazolidinediones Chemical class 0.000 claims 1
• 230000008673 vomiting Effects 0.000 claims 1
• 229940075420 xanthine Drugs 0.000 claims 1