CN1328277C - 取代的嘧啶酮和吡啶酮化合物和它们的应用 - Google Patents
取代的嘧啶酮和吡啶酮化合物和它们的应用 Download PDFInfo
- Publication number
- CN1328277C CN1328277C CNB971815585A CN97181558A CN1328277C CN 1328277 C CN1328277 C CN 1328277C CN B971815585 A CNB971815585 A CN B971815585A CN 97181558 A CN97181558 A CN 97181558A CN 1328277 C CN1328277 C CN 1328277C
- Authority
- CN
- China
- Prior art keywords
- amino
- group
- alkyl
- pyridyl
- phenyl
- Prior art date
- 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
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 title claims abstract description 144
- YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 title abstract description 8
- 150000005299 pyridinones Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 140
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 108090001007 Interleukin-8 Proteins 0.000 claims abstract description 18
- 108090001005 Interleukin-6 Proteins 0.000 claims abstract description 14
- 206010061218 Inflammation Diseases 0.000 claims abstract description 9
- 230000004054 inflammatory process Effects 0.000 claims abstract description 9
- 238000011282 treatment Methods 0.000 claims abstract description 9
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 8
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- -1 heterocyclic radical Chemical class 0.000 claims description 1885
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 607
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 244
- 229910052736 halogen Inorganic materials 0.000 claims description 233
- 150000002367 halogens Chemical class 0.000 claims description 233
- 125000001072 heteroaryl group Chemical group 0.000 claims description 175
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 160
- 125000000217 alkyl group Chemical group 0.000 claims description 118
- 125000003118 aryl group Chemical group 0.000 claims description 109
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 106
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 100
- 239000001257 hydrogen Substances 0.000 claims description 91
- 229910052739 hydrogen Inorganic materials 0.000 claims description 91
- 238000002360 preparation method Methods 0.000 claims description 89
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 86
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 84
- 238000006243 chemical reaction Methods 0.000 claims description 79
- 125000003368 amide group Chemical group 0.000 claims description 76
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 73
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 66
- ODFJOVXVLFUVNQ-UHFFFAOYSA-N acetarsol Chemical compound CC(=O)NC1=CC([As](O)(O)=O)=CC=C1O ODFJOVXVLFUVNQ-UHFFFAOYSA-N 0.000 claims description 61
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 60
- 125000001188 haloalkyl group Chemical group 0.000 claims description 59
- 239000000203 mixture Substances 0.000 claims description 55
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 49
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 38
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 34
- 125000004414 alkyl thio group Chemical group 0.000 claims description 33
- 125000005418 aryl aryl group Chemical group 0.000 claims description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 33
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 30
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 30
- 108010002352 Interleukin-1 Proteins 0.000 claims description 25
- 125000003282 alkyl amino group Chemical group 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 20
- 239000003814 drug Substances 0.000 claims description 19
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 125000000623 heterocyclic group Chemical group 0.000 claims description 17
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 230000000694 effects Effects 0.000 claims description 14
- 239000001301 oxygen Substances 0.000 claims description 14
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 11
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 9
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 9
- 206010040070 Septic Shock Diseases 0.000 claims description 8
- 239000005864 Sulphur Substances 0.000 claims description 8
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 claims description 8
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 8
- CCMHVACSTGTQTB-NRFANRHFSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@H](N)CNC=1N(C(C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)C1=CC=CC=C1 CCMHVACSTGTQTB-NRFANRHFSA-N 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 239000011737 fluorine Substances 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 7
- 206010006895 Cachexia Diseases 0.000 claims description 6
- 241000701022 Cytomegalovirus Species 0.000 claims description 6
- 230000002490 cerebral effect Effects 0.000 claims description 6
- 230000006866 deterioration Effects 0.000 claims description 6
- 208000014674 injury Diseases 0.000 claims description 6
- 210000003205 muscle Anatomy 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- 230000008733 trauma Effects 0.000 claims description 6
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
- 208000004232 Enteritis Diseases 0.000 claims description 5
- 102000051325 Glucagon Human genes 0.000 claims description 5
- 108060003199 Glucagon Proteins 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 5
- 206010063837 Reperfusion injury Diseases 0.000 claims description 5
- 208000026500 emaciation Diseases 0.000 claims description 5
- 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 5
- 229960004666 glucagon Drugs 0.000 claims description 5
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 5
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000031886 HIV Infections Diseases 0.000 claims description 4
- 206010020164 HIV infection CDC Group III Diseases 0.000 claims description 4
- 241000713772 Human immunodeficiency virus 1 Species 0.000 claims description 4
- 241000713340 Human immunodeficiency virus 2 Species 0.000 claims description 4
- 206010031252 Osteomyelitis Diseases 0.000 claims description 4
- 208000001132 Osteoporosis Diseases 0.000 claims description 4
- 208000033464 Reiter syndrome Diseases 0.000 claims description 4
- 206010040047 Sepsis Diseases 0.000 claims description 4
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 4
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 208000019664 bone resorption disease Diseases 0.000 claims description 4
- 208000028867 ischemia Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 150000003254 radicals Chemical class 0.000 claims description 4
- 208000002574 reactive arthritis Diseases 0.000 claims description 4
- 230000036303 septic shock Effects 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 3
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 206010063094 Cerebral malaria Diseases 0.000 claims description 3
- 206010012442 Dermatitis contact Diseases 0.000 claims description 3
- 208000007514 Herpes zoster Diseases 0.000 claims description 3
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 208000000112 Myalgia Diseases 0.000 claims description 3
- 208000010191 Osteitis Deformans Diseases 0.000 claims description 3
- 208000027868 Paget disease Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 3
- 206010037660 Pyrexia Diseases 0.000 claims description 3
- 241000700584 Simplexvirus Species 0.000 claims description 3
- 206010046851 Uveitis Diseases 0.000 claims description 3
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 3
- 208000010247 contact dermatitis Diseases 0.000 claims description 3
- 206010022000 influenza Diseases 0.000 claims description 3
- 208000027202 mammary Paget disease Diseases 0.000 claims description 3
- 208000010125 myocardial infarction Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- 125000004149 thio group Chemical group *S* 0.000 claims description 3
- 241000701161 unidentified adenovirus Species 0.000 claims description 3
- OEUZJGSBWARDHK-UHFFFAOYSA-N 2-(2-anilinoethylamino)-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCCNC1=CC=CC=C1 OEUZJGSBWARDHK-UHFFFAOYSA-N 0.000 claims description 2
- AKCSCNNVLSSWOX-UHFFFAOYSA-N 2-(benzylamino)-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCC1=CC=CC=C1 AKCSCNNVLSSWOX-UHFFFAOYSA-N 0.000 claims description 2
- DDVPIZNSURFYGG-NRFANRHFSA-N 2-[[(3s)-3-amino-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C1([C@@H](N)CCNC=2N(C(C(C=3C=CC(F)=CC=3)=C(C=3C=CN=CC=3)N=2)=O)C)=CC=CC=C1 DDVPIZNSURFYGG-NRFANRHFSA-N 0.000 claims description 2
- HFNYLNWRGDTVAI-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-[(3-hydroxy-3-phenylpropyl)amino]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCCC(O)C1=CC=CC=C1 HFNYLNWRGDTVAI-UHFFFAOYSA-N 0.000 claims description 2
- ZDWDPACJGPUXFV-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-[2-(4-fluorophenyl)ethylamino]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCCC1=CC=C(F)C=C1 ZDWDPACJGPUXFV-UHFFFAOYSA-N 0.000 claims description 2
- NKBHQDAYDPJEHQ-QFIPXVFZSA-N N[C@H](CNC1=NC(=C(C(N1C)=O)C1=CC(=CC=C1)CN)C1=CC=NC=C1)CC1=CC=CC=C1 Chemical class N[C@H](CNC1=NC(=C(C(N1C)=O)C1=CC(=CC=C1)CN)C1=CC=NC=C1)CC1=CC=CC=C1 NKBHQDAYDPJEHQ-QFIPXVFZSA-N 0.000 claims description 2
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 2
- LIUSGUDNCQIOFR-QFIPXVFZSA-N n-[(2s)-1-[[5-(4-fluorophenyl)-1-methyl-6-oxo-4-pyridin-4-ylpyrimidin-2-yl]amino]-3-phenylpropan-2-yl]-2-hydroxyacetamide Chemical class C([C@@H](CNC=1N(C(C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)NC(=O)CO)C1=CC=CC=C1 LIUSGUDNCQIOFR-QFIPXVFZSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims 10
- 230000036470 plasma concentration Effects 0.000 claims 4
- 208000024827 Alzheimer disease Diseases 0.000 claims 2
- 206010008190 Cerebrovascular accident Diseases 0.000 claims 2
- 102000010907 Cyclooxygenase 2 Human genes 0.000 claims 2
- 108010037462 Cyclooxygenase 2 Proteins 0.000 claims 2
- 206010036631 Presenile dementia Diseases 0.000 claims 2
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims 2
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims 2
- 208000006011 Stroke Diseases 0.000 claims 2
- 230000003042 antagnostic effect Effects 0.000 claims 2
- 208000027753 pain disease Diseases 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 150000003180 prostaglandins Chemical class 0.000 claims 2
- XHZRRDSZCUTQKE-UHFFFAOYSA-N 2-[(2-amino-2-methyl-3-phenylpropyl)amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCC(C)(N)CC1=CC=CC=C1 XHZRRDSZCUTQKE-UHFFFAOYSA-N 0.000 claims 1
- DDVPIZNSURFYGG-UHFFFAOYSA-N 2-[(3-amino-3-phenylpropyl)amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCCC(N)C1=CC=CC=C1 DDVPIZNSURFYGG-UHFFFAOYSA-N 0.000 claims 1
- CCMHVACSTGTQTB-OAQYLSRUSA-N 2-[[(2r)-2-amino-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@@H](N)CNC=1N(C(C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)C1=CC=CC=C1 CCMHVACSTGTQTB-OAQYLSRUSA-N 0.000 claims 1
- ZNVSAAACVGXBTD-UZUQRXQVSA-N 2-[[(2r,3r)-3-amino-2-methyl-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@@H](C)[C@@H](N)C=1C=CC=CC=1)NC(N(C(=O)C=1C=2C=CC(F)=CC=2)C)=NC=1C1=CC=NC=C1 ZNVSAAACVGXBTD-UZUQRXQVSA-N 0.000 claims 1
- FVKOZHOHAXIKKN-QFIPXVFZSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-3-ethyl-5-(4-fluorophenyl)-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@H](N)CNC=1N(C(C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N=1)=O)CC)C1=CC=CC=C1 FVKOZHOHAXIKKN-QFIPXVFZSA-N 0.000 claims 1
- SRTMKYZQMSTUPY-DEOSSOPVSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-3-methyl-5-(3-propan-2-ylphenyl)-6-pyridin-4-ylpyrimidin-4-one Chemical class CC(C)C1=CC=CC(C=2C(N(C)C(NC[C@@H](N)CC=3C=CC=CC=3)=NC=2C=2C=CN=CC=2)=O)=C1 SRTMKYZQMSTUPY-DEOSSOPVSA-N 0.000 claims 1
- CVFGZFPGZQTSNR-QFIPXVFZSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-3-methyl-5-(4-methylphenyl)-6-pyridin-4-ylpyrimidin-4-one Chemical class C1=CC(C)=CC=C1C(C(N1C)=O)=C(C=2C=CN=CC=2)N=C1NC[C@@H](N)CC1=CC=CC=C1 CVFGZFPGZQTSNR-QFIPXVFZSA-N 0.000 claims 1
- JJFQTIXLFARPRO-QHCPKHFHSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-3-methyl-5-naphthalen-1-yl-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@H](N)CNC=1N(C(C(C=2C3=CC=CC=C3C=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)C1=CC=CC=C1 JJFQTIXLFARPRO-QHCPKHFHSA-N 0.000 claims 1
- PSGUPCOYEKLVGA-NRFANRHFSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-5-(3-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@H](N)CNC=1N(C(C(C=2C=C(F)C=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)C1=CC=CC=C1 PSGUPCOYEKLVGA-NRFANRHFSA-N 0.000 claims 1
- YFPNLHNUUOEDCA-FQEVSTJZSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-5-(4-fluorophenyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical class C([C@@H](N)CC=1C=CC=CC=1)NC(NC(=O)C=1C=2C=CC(F)=CC=2)=NC=1C1=CC=NC=C1 YFPNLHNUUOEDCA-FQEVSTJZSA-N 0.000 claims 1
- ZNVSAAACVGXBTD-SBUREZEXSA-N 2-[[(2s,3s)-3-amino-2-methyl-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@H](C)[C@H](N)C=1C=CC=CC=1)NC(N(C(=O)C=1C=2C=CC(F)=CC=2)C)=NC=1C1=CC=NC=C1 ZNVSAAACVGXBTD-SBUREZEXSA-N 0.000 claims 1
- DDVPIZNSURFYGG-OAQYLSRUSA-N 2-[[(3r)-3-amino-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C1([C@H](N)CCNC=2N(C(C(C=3C=CC(F)=CC=3)=C(C=3C=CN=CC=3)N=2)=O)C)=CC=CC=C1 DDVPIZNSURFYGG-OAQYLSRUSA-N 0.000 claims 1
- YLBDKLMQLYSQOY-UHFFFAOYSA-N 2-[[2-(aminomethyl)-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCC(CN)CC1=CC=CC=C1 YLBDKLMQLYSQOY-UHFFFAOYSA-N 0.000 claims 1
- XNTSQSMGVQDMIQ-UHFFFAOYSA-N 3-ethyl-5-(4-fluorophenyl)-2-[(2-methyl-3-phenylpropyl)amino]-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(CC)C=1NCC(C)CC1=CC=CC=C1 XNTSQSMGVQDMIQ-UHFFFAOYSA-N 0.000 claims 1
- YEFQCWHRTPNYCU-UHFFFAOYSA-N 3-methyl-2-[(2-methyl-3-phenylpropyl)amino]-5-naphthalen-1-yl-6-pyridin-4-ylpyrimidin-4-one Chemical class C=1C=CC=CC=1CC(C)CNC(N(C(=O)C=1C=2C3=CC=CC=C3C=CC=2)C)=NC=1C1=CC=NC=C1 YEFQCWHRTPNYCU-UHFFFAOYSA-N 0.000 claims 1
- PXDWXQYZBLAGKM-UHFFFAOYSA-N 3-methyl-5-(4-methylphenyl)-2-(3-phenylpropylamino)-6-pyridin-4-ylpyrimidin-4-one Chemical class C1=CC(C)=CC=C1C(C(N1C)=O)=C(C=2C=CN=CC=2)N=C1NCCCC1=CC=CC=C1 PXDWXQYZBLAGKM-UHFFFAOYSA-N 0.000 claims 1
- CHMSJHBKYKOTAQ-UHFFFAOYSA-N 3-phenyl-4-pyridin-4-yl-6-thiophen-2-yl-1h-pyridin-2-one Chemical class C=1C=CC=CC=1C=1C(=O)NC(C=2SC=CC=2)=CC=1C1=CC=NC=C1 CHMSJHBKYKOTAQ-UHFFFAOYSA-N 0.000 claims 1
- RGSHWHLCAVPXJI-UHFFFAOYSA-N 5-(3-fluorophenyl)-3-methyl-2-[(2-methyl-3-phenylpropyl)amino]-6-pyridin-4-ylpyrimidin-4-one Chemical class C=1C=CC=CC=1CC(C)CNC(N(C(=O)C=1C=2C=C(F)C=CC=2)C)=NC=1C1=CC=NC=C1 RGSHWHLCAVPXJI-UHFFFAOYSA-N 0.000 claims 1
- DWRSHNCHSJRCDF-UHFFFAOYSA-N 5-(4-fluorophenyl)-3-methyl-2-[(2-methyl-3-phenylpropyl)amino]-6-pyridin-4-ylpyrimidin-4-one Chemical class C=1C=CC=CC=1CC(C)CNC(N(C(=O)C=1C=2C=CC(F)=CC=2)C)=NC=1C1=CC=NC=C1 DWRSHNCHSJRCDF-UHFFFAOYSA-N 0.000 claims 1
- GNIPPDJVBAVGBY-VWLOTQADSA-N 5-(4-fluorophenyl)-3-methyl-2-[[(2s)-3-phenyl-2-pyrrolidin-1-ylpropyl]amino]-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@@H](CNC=1N(C(C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)N1CCCC1)C1=CC=CC=C1 GNIPPDJVBAVGBY-VWLOTQADSA-N 0.000 claims 1
- ZNBYFEUDMWGIIM-UHFFFAOYSA-N 6-(4-ethylphenyl)-3-phenyl-4-pyridin-4-yl-1h-pyridin-2-one Chemical class C1=CC(CC)=CC=C1C(NC1=O)=CC(C=2C=CN=CC=2)=C1C1=CC=CC=C1 ZNBYFEUDMWGIIM-UHFFFAOYSA-N 0.000 claims 1
- XANWEWGHAVVMER-UHFFFAOYSA-N 6-(furan-2-yl)-3-phenyl-4-pyridin-4-yl-1h-pyridin-2-one Chemical class C=1C=CC=CC=1C=1C(=O)NC(C=2OC=CC=2)=CC=1C1=CC=NC=C1 XANWEWGHAVVMER-UHFFFAOYSA-N 0.000 claims 1
- WUSGQJKWFQCRNZ-UHFFFAOYSA-N NC(CCNC1=NC(=C(C(N1C)=O)C1=CC(=CC=C1)CN)C1=CC=NC=C1)C1=CC=CC=C1 Chemical class NC(CCNC1=NC(=C(C(N1C)=O)C1=CC(=CC=C1)CN)C1=CC=NC=C1)C1=CC=CC=C1 WUSGQJKWFQCRNZ-UHFFFAOYSA-N 0.000 claims 1
- TYVWGIHOZKIDPF-UHFFFAOYSA-N NCC1=CC=C(C=C1)C1=CC(=C(C(N1)=O)C1=CC=CC=C1)C1=CC=NC=C1 Chemical class NCC1=CC=C(C=C1)C1=CC(=C(C(N1)=O)C1=CC=CC=C1)C1=CC=NC=C1 TYVWGIHOZKIDPF-UHFFFAOYSA-N 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 72
- 201000010099 disease Diseases 0.000 abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 19
- 102000004890 Interleukin-8 Human genes 0.000 abstract description 16
- 239000000543 intermediate Substances 0.000 abstract description 8
- 239000000651 prodrug Substances 0.000 abstract description 8
- 229940002612 prodrug Drugs 0.000 abstract description 8
- 102000003777 Interleukin-1 beta Human genes 0.000 abstract description 6
- 108090000193 Interleukin-1 beta Proteins 0.000 abstract description 6
- 208000002193 Pain Diseases 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 3
- 230000001404 mediated effect Effects 0.000 abstract description 2
- 238000011321 prophylaxis Methods 0.000 abstract 2
- GOZMBJCYMQQACI-UHFFFAOYSA-N 6,7-dimethyl-3-[[methyl-[2-[methyl-[[1-[3-(trifluoromethyl)phenyl]indol-3-yl]methyl]amino]ethyl]amino]methyl]chromen-4-one;dihydrochloride Chemical compound Cl.Cl.C=1OC2=CC(C)=C(C)C=C2C(=O)C=1CN(C)CCN(C)CC(C1=CC=CC=C11)=CN1C1=CC=CC(C(F)(F)F)=C1 GOZMBJCYMQQACI-UHFFFAOYSA-N 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 134
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 100
- 239000002585 base Substances 0.000 description 86
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 83
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 75
- 239000000243 solution Substances 0.000 description 53
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 50
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 47
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 238000001704 evaporation Methods 0.000 description 41
- 230000008020 evaporation Effects 0.000 description 41
- 238000005160 1H NMR spectroscopy Methods 0.000 description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 37
- 239000003513 alkali Substances 0.000 description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- 125000003545 alkoxy group Chemical group 0.000 description 29
- 239000011541 reaction mixture Substances 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 24
- 125000004076 pyridyl group Chemical group 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 102000000589 Interleukin-1 Human genes 0.000 description 23
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 238000007429 general method Methods 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 22
- 229910002027 silica gel Inorganic materials 0.000 description 22
- 229960001866 silicon dioxide Drugs 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- 125000004663 dialkyl amino group Chemical group 0.000 description 21
- 239000000047 product Substances 0.000 description 21
- 150000003222 pyridines Chemical class 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 229910052799 carbon Inorganic materials 0.000 description 20
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 20
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- 125000002905 alkanoylamido group Chemical group 0.000 description 18
- 150000001721 carbon Chemical group 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
- 125000003710 aryl alkyl group Chemical group 0.000 description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 15
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 description 15
- 229940096397 interleukin-8 Drugs 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 14
- 150000001412 amines Chemical class 0.000 description 14
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 13
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 13
- 238000003818 flash chromatography Methods 0.000 description 13
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 13
- 239000002994 raw material Substances 0.000 description 13
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 150000001335 aliphatic alkanes Chemical class 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 12
- 102000004889 Interleukin-6 Human genes 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- 125000004122 cyclic group Chemical group 0.000 description 11
- 238000000605 extraction Methods 0.000 description 11
- 229940100601 interleukin-6 Drugs 0.000 description 11
- 102000004127 Cytokines Human genes 0.000 description 10
- 108090000695 Cytokines Proteins 0.000 description 10
- 125000002252 acyl group Chemical group 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 238000010828 elution Methods 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 10
- 238000005406 washing Methods 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 9
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 9
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 239000012141 concentrate Substances 0.000 description 9
- 229910001873 dinitrogen Inorganic materials 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 8
- 235000008504 concentrate Nutrition 0.000 description 8
- 239000012280 lithium aluminium hydride Substances 0.000 description 8
- 238000000746 purification Methods 0.000 description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 7
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
- 239000000908 ammonium hydroxide Substances 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 7
- 238000007363 ring formation reaction Methods 0.000 description 7
- 239000012312 sodium hydride Substances 0.000 description 7
- 229910000104 sodium hydride Inorganic materials 0.000 description 7
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 7
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 6
- LYUQWQRTDLVQGA-UHFFFAOYSA-N 3-phenylpropylamine Chemical compound NCCCC1=CC=CC=C1 LYUQWQRTDLVQGA-UHFFFAOYSA-N 0.000 description 6
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- 102100040247 Tumor necrosis factor Human genes 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 6
- 125000005956 isoquinolyl group Chemical group 0.000 description 6
- 210000004493 neutrocyte Anatomy 0.000 description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- ICSNLGPSRYBMBD-UHFFFAOYSA-N alpha-aminopyridine Natural products NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 5
- 125000004475 heteroaralkyl group Chemical group 0.000 description 5
- BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 229920006395 saturated elastomer Polymers 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 4
- PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 229940123413 Angiotensin II antagonist Drugs 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 102000004877 Insulin Human genes 0.000 description 4
- 108090001061 Insulin Proteins 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 125000003342 alkenyl group Chemical group 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 125000000304 alkynyl group Chemical group 0.000 description 4
- 239000002333 angiotensin II receptor antagonist Substances 0.000 description 4
- 239000004327 boric acid Substances 0.000 description 4
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 4
- QMMFVYPAHWMCMS-UHFFFAOYSA-N dimethylsulfide Substances CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 239000008103 glucose Substances 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- 150000002460 imidazoles Chemical class 0.000 description 4
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 4
- 239000012053 oil suspension Substances 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical group [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 238000010025 steaming Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 238000010189 synthetic method Methods 0.000 description 4
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 4
- CXFFQOZYXJHZNJ-VIFPVBQESA-N (2s)-3-phenylpropane-1,2-diamine Chemical compound NC[C@@H](N)CC1=CC=CC=C1 CXFFQOZYXJHZNJ-VIFPVBQESA-N 0.000 description 3
- SVBLNCJETIXIPV-UHFFFAOYSA-N 2-methyl-3-phenylpropan-1-amine Chemical compound NCC(C)CC1=CC=CC=C1 SVBLNCJETIXIPV-UHFFFAOYSA-N 0.000 description 3
- APBUYIXVZXDFQD-UHFFFAOYSA-N 3-ethyl-5-(4-fluorophenyl)-2-methylsulfonyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C=1C=C(F)C=CC=1C=1C(=O)N(CC)C(S(C)(=O)=O)=NC=1C1=CC=NC=C1 APBUYIXVZXDFQD-UHFFFAOYSA-N 0.000 description 3
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 206010003497 Asphyxia Diseases 0.000 description 3
- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 150000001350 alkyl halides Chemical class 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 3
- 244000309464 bull Species 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 150000004985 diamines Chemical class 0.000 description 3
- 238000007327 hydrogenolysis reaction Methods 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 3
- 125000004043 oxo group Chemical group O=* 0.000 description 3
- 238000005192 partition Methods 0.000 description 3
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 3
- 235000015320 potassium carbonate Nutrition 0.000 description 3
- 150000003141 primary amines Chemical class 0.000 description 3
- 230000004224 protection Effects 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
- HZDNNJABYXNPPV-UHFFFAOYSA-N (2-chloro-2-oxoethyl) acetate Chemical compound CC(=O)OCC(Cl)=O HZDNNJABYXNPPV-UHFFFAOYSA-N 0.000 description 2
- ZNOREXRHKZXVPC-UHFFFAOYSA-N (4-fluorophenyl) acetate Chemical compound CC(=O)OC1=CC=C(F)C=C1 ZNOREXRHKZXVPC-UHFFFAOYSA-N 0.000 description 2
- 125000006730 (C2-C5) alkynyl group Chemical group 0.000 description 2
- WAZWPWNJVULLRQ-UHFFFAOYSA-N 1,1-dimethyl-2-(3-phenylpropyl)hydrazine Chemical compound CN(C)NCCCC1=CC=CC=C1 WAZWPWNJVULLRQ-UHFFFAOYSA-N 0.000 description 2
- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 2
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 2
- WQYIZHQLCTYCQB-FTBISJDPSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-3-ethyl-5-(4-fluorophenyl)-6-pyridin-4-ylpyrimidin-4-one;hydrochloride Chemical class Cl.C([C@H](N)CNC=1N(C(C(C=2C=CC(F)=CC=2)=C(C=2C=CN=CC=2)N=1)=O)CC)C1=CC=CC=C1 WQYIZHQLCTYCQB-FTBISJDPSA-N 0.000 description 2
- FFNVQNRYTPFDDP-UHFFFAOYSA-N 2-cyanopyridine Chemical compound N#CC1=CC=CC=N1 FFNVQNRYTPFDDP-UHFFFAOYSA-N 0.000 description 2
- GESDOWMVVXJZGL-UHFFFAOYSA-N 2-methyl-3-phenylpropane-1,2-diamine Chemical compound NCC(N)(C)CC1=CC=CC=C1 GESDOWMVVXJZGL-UHFFFAOYSA-N 0.000 description 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- LUYOTDGHRZDHDB-UHFFFAOYSA-N 3-(2-methylphenyl)propan-1-amine Chemical compound CC1=CC=CC=C1CCCN LUYOTDGHRZDHDB-UHFFFAOYSA-N 0.000 description 2
- XXQAOLBKCBCORI-UHFFFAOYSA-N 3-ethyl-5-(4-fluorophenyl)-2-[(2-methyl-3-phenylpropyl)amino]-6-pyridin-4-ylpyrimidin-4-one hydrochloride Chemical class Cl.N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(CC)C=1NCC(C)CC1=CC=CC=C1 XXQAOLBKCBCORI-UHFFFAOYSA-N 0.000 description 2
- IJOYKDUPWGVGRQ-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-methyl-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical class C=1C=C(F)C=CC=1C=1C(=O)NC(C)=NC=1C1=CC=NC=C1 IJOYKDUPWGVGRQ-UHFFFAOYSA-N 0.000 description 2
- HGZNHSCWZGDVOR-UHFFFAOYSA-N 5-(4-fluorophenyl)-3-methyl-2-[(2-methyl-3-phenylpropyl)amino]-6-pyridin-4-ylpyrimidin-4-one hydrochloride Chemical class Cl.C=1C=CC=CC=1CC(C)CNC(N(C(=O)C=1C=2C=CC(F)=CC=2)C)=NC=1C1=CC=NC=C1 HGZNHSCWZGDVOR-UHFFFAOYSA-N 0.000 description 2
- RQTQZVFHWWTISL-UHFFFAOYSA-N 6-pyridin-4-yl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound N1C(=S)NC(=O)C=C1C1=CC=NC=C1 RQTQZVFHWWTISL-UHFFFAOYSA-N 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N Butyraldehyde Chemical compound CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- JIJZFKGMXOFCLG-UHFFFAOYSA-N CN(C(C(C1=CC(CN)=CC=C1)=C(C1=CC=NC=C1)N1)=O)C1=O Chemical compound CN(C(C(C1=CC(CN)=CC=C1)=C(C1=CC=NC=C1)N1)=O)C1=O JIJZFKGMXOFCLG-UHFFFAOYSA-N 0.000 description 2
- 102000019034 Chemokines Human genes 0.000 description 2
- 108010012236 Chemokines Proteins 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- BSWMBKMPOLOMEI-UHFFFAOYSA-N ClC1=NC(=C(C(N1C)=O)C1=CC(=CC=C1)CN)C1=CC=NC=C1 Chemical class ClC1=NC(=C(C(N1C)=O)C1=CC(=CC=C1)CN)C1=CC=NC=C1 BSWMBKMPOLOMEI-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- ZDQWESQEGGJUCH-UHFFFAOYSA-N Diisopropyl adipate Chemical compound CC(C)OC(=O)CCCCC(=O)OC(C)C ZDQWESQEGGJUCH-UHFFFAOYSA-N 0.000 description 2
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 2
- DULCUDSUACXJJC-UHFFFAOYSA-N Ethyl phenylacetate Chemical compound CCOC(=O)CC1=CC=CC=C1 DULCUDSUACXJJC-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010063919 Glucagon Receptors Proteins 0.000 description 2
- 102100040890 Glucagon receptor Human genes 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 2
- XGEGHDBEHXKFPX-UHFFFAOYSA-N N-methyl urea Chemical group CNC(N)=O XGEGHDBEHXKFPX-UHFFFAOYSA-N 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical compound CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 206010039361 Sacroiliitis Diseases 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 125000005236 alkanoylamino group Chemical group 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 2
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 230000004110 gluconeogenesis Effects 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
- 229960001238 methylnicotinate Drugs 0.000 description 2
- 210000001616 monocyte Anatomy 0.000 description 2
- 239000012434 nucleophilic reagent Substances 0.000 description 2
- 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 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 2
- PJGSXYOJTGTZAV-UHFFFAOYSA-N pinacolone Chemical compound CC(=O)C(C)(C)C PJGSXYOJTGTZAV-UHFFFAOYSA-N 0.000 description 2
- 150000003053 piperidines Chemical class 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 2
- OKULHRWWYCFJAB-UHFFFAOYSA-N pyrimidine-4-carbaldehyde Chemical compound O=CC1=CC=NC=N1 OKULHRWWYCFJAB-UHFFFAOYSA-N 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000000452 restraining effect Effects 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 150000003335 secondary amines Chemical class 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
- 125000002769 thiazolinyl group Chemical group 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 229950004288 tosilate Drugs 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229910052720 vanadium Inorganic materials 0.000 description 2
- 230000017613 viral reproduction Effects 0.000 description 2
- JSLZUBLGGPEVQN-DIPNUNPCSA-N (2r)-4-methyl-2-propan-2-yl-2-[2-[4-[4-[2-(3,4,5-trimethoxyphenyl)ethyl]piperazin-1-yl]butoxy]phenyl]-1,4-benzothiazin-3-one Chemical compound COC1=C(OC)C(OC)=CC(CCN2CCN(CCCCOC=3C(=CC=CC=3)[C@@]3(C(N(C)C4=CC=CC=C4S3)=O)C(C)C)CC2)=C1 JSLZUBLGGPEVQN-DIPNUNPCSA-N 0.000 description 1
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
- IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 1
- UNKNAPRNXOMOJQ-NSHDSACASA-N (2s)-2-n,2-n-dimethyl-3-phenylpropane-1,2-diamine Chemical compound CN(C)[C@H](CN)CC1=CC=CC=C1 UNKNAPRNXOMOJQ-NSHDSACASA-N 0.000 description 1
- SDUWCESJQGBSND-IONNQARKSA-N (2s,3r)-3-amino-2-methyl-3-phenylpropanamide Chemical compound NC(=O)[C@@H](C)[C@@H](N)C1=CC=CC=C1 SDUWCESJQGBSND-IONNQARKSA-N 0.000 description 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
- IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 1
- MMWRGWQTAMNAFC-UHFFFAOYSA-N 1,2-dihydropyridine Chemical class C1NC=CC=C1 MMWRGWQTAMNAFC-UHFFFAOYSA-N 0.000 description 1
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical compound C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical class C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
- UEMGWPRHOOEKTA-UHFFFAOYSA-N 1,3-difluorobenzene Chemical compound FC1=CC=CC(F)=C1 UEMGWPRHOOEKTA-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- RIFKADJTWUGDOV-UHFFFAOYSA-N 1-cyclohexylethanone Chemical compound CC(=O)C1CCCCC1 RIFKADJTWUGDOV-UHFFFAOYSA-N 0.000 description 1
- PLDPCRJUQLPMNU-UHFFFAOYSA-N 1-phenylpropane-1,3-diamine Chemical compound NCCC(N)C1=CC=CC=C1 PLDPCRJUQLPMNU-UHFFFAOYSA-N 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical class O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- JBISHCXLCGVPGW-UHFFFAOYSA-N 2,6-dichlorobenzenethiol Chemical compound SC1=C(Cl)C=CC=C1Cl JBISHCXLCGVPGW-UHFFFAOYSA-N 0.000 description 1
- DDNZMSHBGPIXPX-UHFFFAOYSA-N 2,6-dimethylpyrimidine-4-carbaldehyde Chemical compound CC1=CC(C=O)=NC(C)=N1 DDNZMSHBGPIXPX-UHFFFAOYSA-N 0.000 description 1
- HJHGQAVUFBUUKT-UHFFFAOYSA-N 2-(2-anilinoethylsulfanyl)-5-(4-fluorophenyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical class C1=CC(F)=CC=C1C(C(N1)=O)=C(C=2C=CN=CC=2)N=C1SCCNC1=CC=CC=C1 HJHGQAVUFBUUKT-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- FVCUMBANMRZGOR-RPQSWWTGSA-N 2-[[(2r,3r)-3-amino-2-methyl-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one;hydrochloride Chemical class Cl.C([C@@H](C)[C@@H](N)C=1C=CC=CC=1)NC(N(C(=O)C=1C=2C=CC(F)=CC=2)C)=NC=1C1=CC=NC=C1 FVCUMBANMRZGOR-RPQSWWTGSA-N 0.000 description 1
- ZNVSAAACVGXBTD-HXOBKFHXSA-N 2-[[(2r,3s)-3-amino-2-methyl-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C([C@@H](C)[C@H](N)C=1C=CC=CC=1)NC(N(C(=O)C=1C=2C=CC(F)=CC=2)C)=NC=1C1=CC=NC=C1 ZNVSAAACVGXBTD-HXOBKFHXSA-N 0.000 description 1
- SFLDCZPRXDZTAM-BDQAORGHSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-5-(4-fluorophenyl)-6-pyridin-4-yl-1h-pyrimidin-4-one;hydrochloride Chemical class Cl.C([C@@H](N)CC=1C=CC=CC=1)NC(NC(=O)C=1C=2C=CC(F)=CC=2)=NC=1C1=CC=NC=C1 SFLDCZPRXDZTAM-BDQAORGHSA-N 0.000 description 1
- FVCUMBANMRZGOR-DQFHVVJASA-N 2-[[(2s,3s)-3-amino-2-methyl-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one;hydrochloride Chemical class Cl.C([C@H](C)[C@H](N)C=1C=CC=CC=1)NC(N(C(=O)C=1C=2C=CC(F)=CC=2)C)=NC=1C1=CC=NC=C1 FVCUMBANMRZGOR-DQFHVVJASA-N 0.000 description 1
- GQMOKEAIBBFTRY-ZMBIFBSDSA-N 2-[[(3r)-3-amino-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one;hydrochloride Chemical class Cl.C1([C@H](N)CCNC=2N(C(C(C=3C=CC(F)=CC=3)=C(C=3C=CN=CC=3)N=2)=O)C)=CC=CC=C1 GQMOKEAIBBFTRY-ZMBIFBSDSA-N 0.000 description 1
- GQMOKEAIBBFTRY-BOXHHOBZSA-N 2-[[(3s)-3-amino-3-phenylpropyl]amino]-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one;hydrochloride Chemical class Cl.C1([C@@H](N)CCNC=2N(C(C(C=3C=CC(F)=CC=3)=C(C=3C=CN=CC=3)N=2)=O)C)=CC=CC=C1 GQMOKEAIBBFTRY-BOXHHOBZSA-N 0.000 description 1
- OBSIQMZKFXFYLV-UHFFFAOYSA-N 2-amino-3-phenylpropanamide Chemical compound NC(=O)C(N)CC1=CC=CC=C1 OBSIQMZKFXFYLV-UHFFFAOYSA-N 0.000 description 1
- XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical class NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 description 1
- RVRPMUDSNHVUES-UHFFFAOYSA-N 2-amino-5-(4-fluorophenyl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C=1C=C(F)C=CC=1C=1C(=O)N(C)C(N)=NC=1C1=CC=NC=C1 RVRPMUDSNHVUES-UHFFFAOYSA-N 0.000 description 1
- LASITSQBIPSEQU-UHFFFAOYSA-N 2-amino-5-(4-fluorophenyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical class C=1C=C(F)C=CC=1C=1C(=O)NC(N)=NC=1C1=CC=NC=C1 LASITSQBIPSEQU-UHFFFAOYSA-N 0.000 description 1
- OFUFXTHGZWIDDB-UHFFFAOYSA-N 2-chloroquinoline Chemical compound C1=CC=CC2=NC(Cl)=CC=C21 OFUFXTHGZWIDDB-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- JJKWHOSQTYYFAE-UHFFFAOYSA-N 2-methoxyacetyl chloride Chemical class COCC(Cl)=O JJKWHOSQTYYFAE-UHFFFAOYSA-N 0.000 description 1
- ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 description 1
- SUMAWDZJEIQACJ-UHFFFAOYSA-N 2-methylpyridine-4-carbaldehyde Chemical compound CC1=CC(C=O)=CC=N1 SUMAWDZJEIQACJ-UHFFFAOYSA-N 0.000 description 1
- BXHGNAADUUXBKK-UHFFFAOYSA-N 2-methylpyrimidine-4-carbaldehyde Chemical compound CC1=NC=CC(C=O)=N1 BXHGNAADUUXBKK-UHFFFAOYSA-N 0.000 description 1
- DHJWCAYNEYUEOZ-UHFFFAOYSA-N 2-nitropyridine-4-carbaldehyde Chemical compound [O-][N+](=O)C1=CC(C=O)=CC=N1 DHJWCAYNEYUEOZ-UHFFFAOYSA-N 0.000 description 1
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical class NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 1
- WXACXEAGPYTHHG-UHFFFAOYSA-N 3-(2-fluorophenyl)propane-1,1-diamine Chemical compound NC(CCC1=C(C=CC=C1)F)N WXACXEAGPYTHHG-UHFFFAOYSA-N 0.000 description 1
- RMDBHIHGJNGKDD-UHFFFAOYSA-N 3-(2-methylphenyl)prop-2-enenitrile Chemical compound CC1=CC=CC=C1C=CC#N RMDBHIHGJNGKDD-UHFFFAOYSA-N 0.000 description 1
- WCFJUSRQHZPVKY-UHFFFAOYSA-N 3-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound CC(C)(C)OC(=O)NCCC(O)=O WCFJUSRQHZPVKY-UHFFFAOYSA-N 0.000 description 1
- VTSFNCCQCOEPKF-UHFFFAOYSA-N 3-amino-1h-pyridin-2-one Chemical compound NC1=CC=CN=C1O VTSFNCCQCOEPKF-UHFFFAOYSA-N 0.000 description 1
- SDUWCESJQGBSND-UHFFFAOYSA-N 3-amino-2-methyl-3-phenylpropanamide Chemical compound NC(=O)C(C)C(N)C1=CC=CC=C1 SDUWCESJQGBSND-UHFFFAOYSA-N 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- GIYIUIQNXYJAIZ-UHFFFAOYSA-N 3-phenyl-4-pyridin-4-yl-1h-pyridin-2-one Chemical class C=1C=CC=CC=1C=1C(=O)NC=CC=1C1=CC=NC=C1 GIYIUIQNXYJAIZ-UHFFFAOYSA-N 0.000 description 1
- MFEILWXBDBCWKF-UHFFFAOYSA-N 3-phenylpropanoyl chloride Chemical compound ClC(=O)CCC1=CC=CC=C1 MFEILWXBDBCWKF-UHFFFAOYSA-N 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- YQDGQEKUTLYWJU-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinoline Chemical group C1=CC=C2CCCCC2=N1 YQDGQEKUTLYWJU-UHFFFAOYSA-N 0.000 description 1
- NRJQQWLOHWBFKN-UHFFFAOYSA-N 5-(2-fluorophenyl)-2-[2-(2-fluorophenyl)ethylamino]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C(=CC=CC=2)F)C(=O)N(C)C=1NCCC1=CC=CC=C1F NRJQQWLOHWBFKN-UHFFFAOYSA-N 0.000 description 1
- RSMIPNZYFKAFAT-UHFFFAOYSA-N 5-(2-fluorophenyl)-2-[2-(3-fluorophenyl)ethylamino]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C(=CC=CC=2)F)C(=O)N(C)C=1NCCC1=CC=CC(F)=C1 RSMIPNZYFKAFAT-UHFFFAOYSA-N 0.000 description 1
- DAMZFIYOEBDWLN-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-(3-phenylpropylamino)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical class C1=CC(F)=CC=C1C(C(N1)=O)=C(C=2C=CN=CC=2)N=C1NCCCC1=CC=CC=C1 DAMZFIYOEBDWLN-UHFFFAOYSA-N 0.000 description 1
- BRYBZPBPVDEMJR-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-(4-phenylbutan-2-ylamino)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical compound N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)NC=1NC(C)CCC1=CC=CC=C1 BRYBZPBPVDEMJR-UHFFFAOYSA-N 0.000 description 1
- IKCCKTOOPQXTDO-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-[(3-hydroxy-2,2-dimethylpropyl)amino]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical class C=1C=C(F)C=CC=1C=1C(=O)N(C)C(NCC(C)(C)CO)=NC=1C1=CC=NC=C1 IKCCKTOOPQXTDO-UHFFFAOYSA-N 0.000 description 1
- MVXWMOKYXJDFJW-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-hydrazinyl-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical class C=1C=C(F)C=CC=1C=1C(=O)NC(NN)=NC=1C1=CC=NC=C1 MVXWMOKYXJDFJW-UHFFFAOYSA-N 0.000 description 1
- PSYGBMJCUYWINR-UHFFFAOYSA-N 5-(4-fluorophenyl)-2-phenyl-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical class C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)N=C(C=2C=CC=CC=2)NC1=O PSYGBMJCUYWINR-UHFFFAOYSA-N 0.000 description 1
- GSIDPMOHXFYPTM-UHFFFAOYSA-N 5-(4-fluorophenyl)-3-methyl-2-(2-piperazin-1-ylethylamino)-6-pyridin-4-ylpyrimidin-4-one Chemical class N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCCN1CCNCC1 GSIDPMOHXFYPTM-UHFFFAOYSA-N 0.000 description 1
- SPPHZXRQLBRKLZ-UHFFFAOYSA-N 5-(4-fluorophenyl)-3-methyl-2-[(3-phenyl-2-pyrrolidin-1-ylpropyl)amino]-6-pyridin-4-ylpyrimidin-4-one;hydrochloride Chemical class Cl.N=1C(C=2C=CN=CC=2)=C(C=2C=CC(F)=CC=2)C(=O)N(C)C=1NCC(N1CCCC1)CC1=CC=CC=C1 SPPHZXRQLBRKLZ-UHFFFAOYSA-N 0.000 description 1
- JQXCFQMLERNCGN-UHFFFAOYSA-N 5-(4-fluorophenyl)-3-methyl-2-methylsulfonyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C=C(F)C=CC=1C=1C(=O)N(C)C(S(C)(=O)=O)=NC=1C1=CC=NC=C1 JQXCFQMLERNCGN-UHFFFAOYSA-N 0.000 description 1
- GWWVFHNAKJYJQC-UHFFFAOYSA-N 5-(4-fluorophenyl)-6-pyridin-4-yl-1h-pyrimidin-4-one Chemical class C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)N=CNC1=O GWWVFHNAKJYJQC-UHFFFAOYSA-N 0.000 description 1
- CFGHSRDNTILIGJ-UHFFFAOYSA-N 5-(4-fluorophenyl)-6-pyridin-4-yl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)NC(=S)NC1=O CFGHSRDNTILIGJ-UHFFFAOYSA-N 0.000 description 1
- CLNNBQDAAGDAHI-UHFFFAOYSA-N 6-chloro-1h-pyridin-2-one Chemical compound OC1=CC=CC(Cl)=N1 CLNNBQDAAGDAHI-UHFFFAOYSA-N 0.000 description 1
- HQHDCBMGIGHYRE-UHFFFAOYSA-N 6-cyclohexyl-3-phenyl-4-pyridin-4-yl-1h-pyridin-2-one Chemical class C=1C=CC=CC=1C=1C(=O)NC(C2CCCCC2)=CC=1C1=CC=NC=C1 HQHDCBMGIGHYRE-UHFFFAOYSA-N 0.000 description 1
- UVJSZAAUOFNPPG-UHFFFAOYSA-N 6-methylpyrimidine-4-carbaldehyde Chemical compound CC1=CC(C=O)=NC=N1 UVJSZAAUOFNPPG-UHFFFAOYSA-N 0.000 description 1
- NCGODJYXDSDXPL-UHFFFAOYSA-N 6-tert-butyl-3-phenyl-4-pyridin-4-yl-1h-pyridin-2-one Chemical compound C=1C=CC=CC=1C=1C(=O)NC(C(C)(C)C)=CC=1C1=CC=NC=C1 NCGODJYXDSDXPL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- PVFOHMXILQEIHX-UHFFFAOYSA-N 8-[(6-bromo-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-bromophenyl)ethyl]purin-6-amine Chemical compound C=1C=2OCOC=2C=C(Br)C=1SC1=NC=2C(N)=NC=NC=2N1CCC1=CC=CC=C1Br PVFOHMXILQEIHX-UHFFFAOYSA-N 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 244000024893 Amaranthus tricolor Species 0.000 description 1
- 235000014748 Amaranthus tricolor Nutrition 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 108090000145 Bacillolysin Proteins 0.000 description 1
- CJIZJRYWSOLASR-UHFFFAOYSA-N C(CCC)OC(=O)C(C#N)(CC1=CC=CC=C1)N Chemical group C(CCC)OC(=O)C(C#N)(CC1=CC=CC=C1)N CJIZJRYWSOLASR-UHFFFAOYSA-N 0.000 description 1
- GVPQXJJFOHOCNI-UHFFFAOYSA-N CCC(CC)(C#N)OP(O)(O)=O Chemical compound CCC(CC)(C#N)OP(O)(O)=O GVPQXJJFOHOCNI-UHFFFAOYSA-N 0.000 description 1
- XRFHUCOWVLITDH-UHFFFAOYSA-N CSC#N.CSC#N Chemical compound CSC#N.CSC#N XRFHUCOWVLITDH-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 1
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 1
- 206010061216 Infarction Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- VNQMGLFMCKYIJN-UHFFFAOYSA-N N1C(=O)NC(=O)C=C1.[S] Chemical class N1C(=O)NC(=O)C=C1.[S] VNQMGLFMCKYIJN-UHFFFAOYSA-N 0.000 description 1
- 102000035092 Neutral proteases Human genes 0.000 description 1
- 108091005507 Neutral proteases Proteins 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- 206010036030 Polyarthritis Diseases 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- SHLHCWKUGGHALJ-UHFFFAOYSA-N S1C(=CC=C1)CCNC1=NC(=C(C(N1C)=O)C1=CC=C(C=C1)F)C1=CC=NC=C1 Chemical compound S1C(=CC=C1)CCNC1=NC(=C(C(N1C)=O)C1=CC=C(C=C1)F)C1=CC=NC=C1 SHLHCWKUGGHALJ-UHFFFAOYSA-N 0.000 description 1
- 102000040739 Secretory proteins Human genes 0.000 description 1
- 108091058545 Secretory proteins Proteins 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241000534944 Thia Species 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- MUCRYNWJQNHDJH-OADIDDRXSA-N Ursonic acid Chemical compound C1CC(=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C MUCRYNWJQNHDJH-OADIDDRXSA-N 0.000 description 1
- 235000010725 Vigna aconitifolia Nutrition 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- HYOWVAAEQCNGLE-JTQLQIEISA-N alpha-methyl-L-phenylalanine Chemical compound OC(=O)[C@](N)(C)CC1=CC=CC=C1 HYOWVAAEQCNGLE-JTQLQIEISA-N 0.000 description 1
- QUMXDOLUJCHOAY-UHFFFAOYSA-N alpha-methylbenzyl acetate Natural products CC(=O)OC(C)C1=CC=CC=C1 QUMXDOLUJCHOAY-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001409 amidines Chemical class 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 125000004103 aminoalkyl group Chemical group 0.000 description 1
- 238000007281 aminoalkylation reaction Methods 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- LDDQLRUQCUTJBB-UHFFFAOYSA-N ammonium fluoride Chemical compound [NH4+].[F-] LDDQLRUQCUTJBB-UHFFFAOYSA-N 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- CELPHAGZKFMOMR-UHFFFAOYSA-N azanium;dichloromethane;methanol;hydroxide Chemical compound [NH4+].[OH-].OC.ClCCl CELPHAGZKFMOMR-UHFFFAOYSA-N 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 229910052728 basic metal Inorganic materials 0.000 description 1
- 150000003818 basic metals Chemical class 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- CUBCNYWQJHBXIY-UHFFFAOYSA-N benzoic acid;2-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1O CUBCNYWQJHBXIY-UHFFFAOYSA-N 0.000 description 1
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 229940000635 beta-alanine Drugs 0.000 description 1
- MDHYEMXUFSJLGV-UHFFFAOYSA-N beta-phenethyl acetate Natural products CC(=O)OCCC1=CC=CC=C1 MDHYEMXUFSJLGV-UHFFFAOYSA-N 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 125000001246 bromo group Chemical class Br* 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- QNEFNFIKZWUAEQ-UHFFFAOYSA-N carbonic acid;potassium Chemical compound [K].OC(O)=O QNEFNFIKZWUAEQ-UHFFFAOYSA-N 0.000 description 1
- 238000010523 cascade reaction Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 230000004637 cellular stress Effects 0.000 description 1
- 210000001627 cerebral artery Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 210000001612 chondrocyte Anatomy 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005336 cracking Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- ZISUALSZTAEPJH-UHFFFAOYSA-N dimethyl(phenyl)silane Chemical compound C[SiH](C)C1=CC=CC=C1 ZISUALSZTAEPJH-UHFFFAOYSA-N 0.000 description 1
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical group [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 1
- 230000036267 drug metabolism Effects 0.000 description 1
- SQNZJJAZBFDUTD-UHFFFAOYSA-N durene Chemical compound CC1=CC(C)=C(C)C=C1C SQNZJJAZBFDUTD-UHFFFAOYSA-N 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000007350 electrophilic reaction Methods 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- PNZDZRMOBIIQTC-UHFFFAOYSA-N ethanamine;hydron;bromide Chemical compound Br.CCN PNZDZRMOBIIQTC-UHFFFAOYSA-N 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 1
- PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- QGBMSFLTRRZTGI-UHFFFAOYSA-N ethyl(dimethyl)silane Chemical compound CC[SiH](C)C QGBMSFLTRRZTGI-UHFFFAOYSA-N 0.000 description 1
- 229940064982 ethylnicotinate Drugs 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 1
- 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 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical group 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 150000003949 imides Chemical class 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000007574 infarction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 229950001891 iprotiazem Drugs 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000005304 joining Methods 0.000 description 1
- 210000001503 joint Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229920006008 lipopolysaccharide Polymers 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000005228 liver tissue Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229940087646 methanolamine Drugs 0.000 description 1
- KXNXDQIBUXYHME-UHFFFAOYSA-N methyl 2,6-dimethylpyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC(C)=NC(C)=N1 KXNXDQIBUXYHME-UHFFFAOYSA-N 0.000 description 1
- HEUBBCMIYRXETJ-UHFFFAOYSA-N methyl 2-methylpyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC=NC(C)=N1 HEUBBCMIYRXETJ-UHFFFAOYSA-N 0.000 description 1
- KVMIEZCRDGCHLN-UHFFFAOYSA-N methyl 3-amino-2-methyl-3-phenylpropanoate Chemical class COC(=O)C(C)C(N)C1=CC=CC=C1 KVMIEZCRDGCHLN-UHFFFAOYSA-N 0.000 description 1
- NFDAXWQMJFTLRZ-UHFFFAOYSA-N methyl 6-methylpyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC(C)=NC=N1 NFDAXWQMJFTLRZ-UHFFFAOYSA-N 0.000 description 1
- GXZQHMHLHHUHAM-UHFFFAOYSA-N methyl pyrimidine-4-carboxylate Chemical compound COC(=O)C1=CC=NC=N1 GXZQHMHLHHUHAM-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- ZADYXSAHOASLPH-UHFFFAOYSA-N n'-(1-benzofuran-2-yl)-1-phenylpropane-1,3-diamine Chemical compound C=1C2=CC=CC=C2OC=1NCCC(N)C1=CC=CC=C1 ZADYXSAHOASLPH-UHFFFAOYSA-N 0.000 description 1
- HOGDNTQCSIKEEV-UHFFFAOYSA-N n'-hydroxybutanediamide Chemical compound NC(=O)CCC(=O)NO HOGDNTQCSIKEEV-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006093 n-propyl sulfinyl group Chemical group 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- YIBWWKGXGCICAB-UHFFFAOYSA-N phenylstannane Chemical compound [SnH3]C1=CC=CC=C1 YIBWWKGXGCICAB-UHFFFAOYSA-N 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 1
- 229960005439 propantheline bromide Drugs 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- MGCGJBXTNWUHQE-UHFFFAOYSA-N quinoline-4-carbaldehyde Chemical compound C1=CC=C2C(C=O)=CC=NC2=C1 MGCGJBXTNWUHQE-UHFFFAOYSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000007348 radical reaction Methods 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 210000005084 renal tissue Anatomy 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 238000011764 rheumatoid arthritis animal model Methods 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical group CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 1
- 108091007196 stromelysin Proteins 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 210000002437 synoviocyte Anatomy 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical class 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical class O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/16—Central respiratory analeptics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/64—One oxygen atom attached in position 2 or 6
- C07D213/643—2-Phenoxypyridines; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Applications Claiming Priority (6)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3212896P | 1996-12-05 | 1996-12-05 | |
US60/032,128 | 1996-12-05 | ||
US5095097P | 1997-06-13 | 1997-06-13 | |
US60/050,950 | 1997-06-13 | ||
US97605397A | 1997-11-21 | 1997-11-21 | |
US08/976,053 | 1997-11-21 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN1246857A CN1246857A (zh) | 2000-03-08 |
CN1328277C true CN1328277C (zh) | 2007-07-25 |
Family
ID=27364029
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNB971815585A Expired - Fee Related CN1328277C (zh) | 1996-12-05 | 1997-12-04 | 取代的嘧啶酮和吡啶酮化合物和它们的应用 |
Country Status (13)
Country | Link |
---|---|
EP (1) | EP0948496A2 (pt) |
JP (1) | JP2002514196A (pt) |
KR (1) | KR100476586B1 (pt) |
CN (1) | CN1328277C (pt) |
AU (1) | AU735901C (pt) |
BG (1) | BG65129B1 (pt) |
BR (1) | BR9713863A (pt) |
CA (1) | CA2274093C (pt) |
CZ (1) | CZ9902016A3 (pt) |
HU (1) | HUP0001140A3 (pt) |
IL (1) | IL130181A0 (pt) |
NZ (1) | NZ335992A (pt) |
WO (1) | WO1998024780A2 (pt) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110078674A (zh) * | 2019-04-10 | 2019-08-02 | 昆明理工大学 | 一种2-烃基胺基嘧啶酮的制备方法 |
Families Citing this family (93)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6410729B1 (en) * | 1996-12-05 | 2002-06-25 | Amgen Inc. | Substituted pyrimidine compounds and methods of use |
US6613942B1 (en) | 1997-07-01 | 2003-09-02 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
WO1999032121A1 (en) | 1997-12-19 | 1999-07-01 | Smithkline Beecham Corporation | Compounds of heteroaryl substituted imidazole, their pharmaceutical compositions and uses |
US6858617B2 (en) | 1998-05-26 | 2005-02-22 | Smithkline Beecham Corporation | Substituted imidazole compounds |
TWI241298B (en) * | 1998-09-25 | 2005-10-11 | Mitsubishi Chem Corp | Pyrimidone derivatives |
AU1909200A (en) | 1998-11-04 | 2000-05-22 | Smithkline Beecham Corporation | Pyridin-4-yl or pyrimidin-4-yl substituted pyrazines |
GB9910378D0 (en) * | 1999-05-05 | 1999-06-30 | Smithkline Beecham Plc | Novel compounds |
US6503949B1 (en) | 1999-05-17 | 2003-01-07 | Noro Nordisk A/S | Glucagon antagonists/inverse agonists |
US6403596B1 (en) | 1999-06-28 | 2002-06-11 | Merck & Co., Inc. | Substituted pyridones having cytokine inhibitory activity |
DE60020595T2 (de) | 1999-11-23 | 2006-03-16 | Smithkline Beecham Corp. | 3,4-dihydro-(1h)chinazolin-2-on-verbindungen als csbp/p38-kinase-inhibitoren |
US6759410B1 (en) | 1999-11-23 | 2004-07-06 | Smithline Beecham Corporation | 3,4-dihydro-(1H)-quinazolin-2-ones and their use as CSBP/p38 kinase inhibitors |
ATE305787T1 (de) | 1999-11-23 | 2005-10-15 | Smithkline Beecham Corp | 3,4-dihydro-(1h)chinazolin-2-on-verbindungen als csbp/p39-kinase-inhibitoren |
EP1136482A1 (en) | 2000-03-23 | 2001-09-26 | Sanofi-Synthelabo | 2-Amino-3-(alkyl)-pyrimidone derivatives as GSK3beta inhibitors |
JP2005289808A (ja) * | 2000-03-23 | 2005-10-20 | Sanofi-Aventis | 3−置換−4−ピリミドン誘導体 |
EP1136099A1 (en) * | 2000-03-23 | 2001-09-26 | Sanofi-Synthelabo | 2-(Indolylalkylamino)pyrimidone derivatives as GSK3beta inhibitors |
EP1136493A1 (en) * | 2000-03-23 | 2001-09-26 | Sanofi-Synthelabo | 2-(Thienopyridinyl)pyrimidone, 2-(furopyridinyl)pyrimidone 2-(isoquinolinyl)pyrimidone, 2-(pyridoindolyl)pyrimidone and 2-(benzofuropyridinyl)pyrimidone derivatives |
US7189717B2 (en) | 2000-04-26 | 2007-03-13 | Eisai Co., Ltd. | Medicinal compositions promoting bowel movement |
NZ522773A (en) | 2000-06-12 | 2005-06-24 | Eisai Co Ltd | 1,2-dihydropyridine compounds, manufacturing method thereof and use thereof |
US7115608B2 (en) * | 2000-09-19 | 2006-10-03 | Centre National De La Recherche Schentifique | Pyridinone and pyridinethione derivatives having HIV inhibiting properties |
GB0024808D0 (en) * | 2000-10-10 | 2000-11-22 | Smithkline Beecham Plc | Novel compounds |
AU2002223500A1 (en) | 2000-11-17 | 2002-05-27 | Novo-Nordisk A/S | Glucagon antagonists/inverse agonists |
US6706744B2 (en) | 2000-11-17 | 2004-03-16 | Novo Nordisk A/S | Glucagon antagonists/inverse agonists |
US6821960B2 (en) | 2000-11-17 | 2004-11-23 | Noyo Nordisk Pharmaceuticals, Inc. | Glucagon antagonists/inverse agonists |
PT1674456E (pt) | 2001-09-21 | 2008-09-11 | Sanofi Aventis | Utilização de 2-fluoro-3-cetoésteres para preparar 3-fluoro- 6,7,8,9-tetra-hidro-4-h-pirimido[1,2-a]pirimidin-4-onas |
EP1295885A1 (en) * | 2001-09-21 | 2003-03-26 | Sanofi-Synthelabo | Substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido(1,2-a)pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo(1,2-a)pyrimidin-5(1H)one derivatives |
EP1295884A1 (en) * | 2001-09-21 | 2003-03-26 | Sanofi-Synthelabo | 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]Pyrimidin-4-one and 7-Pyrimidinyl-2,3-Dihydroimidazo[1,2-a]Pyrimidin-5(1H)one derivatives |
AU2002337498B2 (en) | 2001-09-21 | 2006-08-10 | Mitsubishi Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
EP1430056B1 (en) | 2001-09-21 | 2005-10-26 | Sanofi-Aventis | Substituted 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1h)one derivatives for neurodegenerative disorders |
TWI301834B (en) * | 2001-10-22 | 2008-10-11 | Eisai R&D Man Co Ltd | Pyrimidone compound and pharmaceutical composition including the same |
TWI330183B (pt) * | 2001-10-22 | 2010-09-11 | Eisai R&D Man Co Ltd | |
US6921762B2 (en) | 2001-11-16 | 2005-07-26 | Amgen Inc. | Substituted indolizine-like compounds and methods of use |
US6881746B2 (en) | 2001-12-03 | 2005-04-19 | Novo Nordick A/S | Glucagon antagonists/inverse agonists |
US6762318B2 (en) | 2001-12-03 | 2004-07-13 | Novo Nordisk A/S | Glucagon antagonists |
EP1458717B1 (en) * | 2001-12-21 | 2005-09-07 | Bayer HealthCare AG | Aroyl pyridinones |
AU2003216591A1 (en) * | 2002-04-10 | 2003-10-20 | Orichid Chemicals And Pharmaceuticals Limited | Amino substituted pyrimidinone derivatives useful in the treatment of inflammation and immunological |
CA2485166A1 (en) | 2002-05-21 | 2003-12-04 | Amgen Inc. | Substituted pyrimidinone and pyridinone compounds |
WO2004004725A2 (en) | 2002-07-09 | 2004-01-15 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Pharmaceutical compositions of anticholinergics and p38 kinase inhibitors in the treatment of respiratory diseases |
US7683069B2 (en) | 2002-12-16 | 2010-03-23 | Mitsubishi Tanabe Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
TWI357408B (en) | 2003-03-26 | 2012-02-01 | Mitsubishi Tanabe Pharma Corp | 3-substituted-4-pyrimidone derivatives |
US20070167621A1 (en) | 2003-04-03 | 2007-07-19 | Pharmacia Corporation | Substituted pyrimidinones |
US7183287B2 (en) * | 2003-04-03 | 2007-02-27 | Pharmacia Corporation | Substituted pyrimidinones |
CA2533684A1 (en) * | 2003-07-25 | 2005-02-10 | Amgen Inc. | Substituted pyridones and pyrimidinones with antiinflammatory properties |
RU2006107553A (ru) * | 2003-08-13 | 2007-09-20 | Такеда Фармасьютикал Компани Лимитед (Jp) | Производные 4-пиримидона и их применение в качестве ингибиторов пептидилпептидаз |
US7429594B2 (en) | 2003-08-20 | 2008-09-30 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
SE0302486D0 (sv) | 2003-09-18 | 2003-09-18 | Astrazeneca Ab | Novel compounds |
EP1557417B1 (en) * | 2003-12-19 | 2007-03-07 | Sanofi-Aventis | Substituted 8'-pyri(mi)dinyl-dihydrospiro-[cycloalkylamine]-pyrimido[1,2-a] pyrimidin-6-one derivatives |
US20060035893A1 (en) | 2004-08-07 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders |
GB0420722D0 (en) | 2004-09-17 | 2004-10-20 | Addex Pharmaceuticals Sa | Novel allosteric modulators |
EP2708531A1 (en) | 2004-10-13 | 2014-03-19 | Pharmacia & Upjohn Company LLC | Crystalline Forms Of 3-[5-Chloro-4-[(2,4-difluorobenzyl) oxy]-6-oxopyrimidin-1(6H)-yl]-N-(2-hydroxyethyl)-4-methylbenzamide |
MX2007007330A (es) | 2004-12-16 | 2007-10-04 | Vertex Pharma | Piridonas de utilidad como inhibidores de quinasas . |
PE20060777A1 (es) | 2004-12-24 | 2006-10-06 | Boehringer Ingelheim Int | Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas |
NZ566799A (en) | 2005-09-14 | 2011-04-29 | Takeda Pharmaceutical | Dipeptidyl peptidase inhibitors for treating diabetes |
CN101360723A (zh) | 2005-09-16 | 2009-02-04 | 武田药品工业株式会社 | 制备嘧啶二酮衍生物的方法 |
AR059898A1 (es) | 2006-03-15 | 2008-05-07 | Janssen Pharmaceutica Nv | Derivados de 3-ciano-piridona 1,4-disustituida y su uso como moduladores alostericos de los receptores mglur2 |
TW200808763A (en) | 2006-05-08 | 2008-02-16 | Astrazeneca Ab | Novel compounds I |
TW200808771A (en) | 2006-05-08 | 2008-02-16 | Astrazeneca Ab | Novel compounds II |
TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
WO2008104752A1 (en) * | 2007-02-26 | 2008-09-04 | Astrazeneca Ab | Dihydropyridones as elastase inhibitors |
TW200845978A (en) | 2007-03-07 | 2008-12-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-tetrahydropyran-phenyl)-pyridin-2-one derivatives |
TW200900065A (en) | 2007-03-07 | 2009-01-01 | Janssen Pharmaceutica Nv | 3-cyano-4-(4-pyridinyloxy-phenyl)-pyridin-2-one derivatives |
EP1992344A1 (en) | 2007-05-18 | 2008-11-19 | Institut Curie | P38 alpha as a therapeutic target in pathologies linked to FGFR3 mutation |
KR20100065191A (ko) | 2007-09-14 | 2010-06-15 | 오르토-맥닐-얀센 파마슈티칼스 인코포레이티드 | 1,3-이치환된 4-(아릴-x-페닐)-1h-피리딘-2-온 |
CN101801951B (zh) | 2007-09-14 | 2013-11-13 | 杨森制药有限公司 | 1’,3’-二取代的-4-苯基-3,4,5,6-四氢-2h,1’h-[1,4’]二吡啶-2’-酮 |
CL2008003301A1 (es) | 2007-11-06 | 2009-10-16 | Astrazeneca Ab | Compuestos derivados de 3,4-dihidropirazina-2-carboxamida, inhibidores de la elastasa de neutrofilos humanos; composiciones farmacéuticas; procesos de preparación de compuestos y composición farmacéutica; y uso en el tratamiento de síndrome de dificultad respiratoria de los adultos, fibrosis quística, cáncer, entre otras. |
RU2510396C2 (ru) | 2008-09-02 | 2014-03-27 | Янссен Фармасьютикалз, Инк. | 3-азабицикло[3.1.0]гексильные производные в качестве модуляторов метаботропных глутаматных рецепторов |
CA2741666C (en) * | 2008-10-31 | 2017-04-11 | Merck Sharp & Dohme Corp. | P2x3, receptor antagonists for treatment of pain |
AU2009319387B2 (en) | 2008-11-28 | 2012-05-10 | Addex Pharma S.A. | Indole and benzoxazine derivatives as modulators of metabotropic glutamate receptors |
TW201036957A (en) | 2009-02-20 | 2010-10-16 | Astrazeneca Ab | Novel salt 628 |
JP5707390B2 (ja) | 2009-05-12 | 2015-04-30 | ジャンセン ファーマシューティカルズ, インコーポレイテッド | 1,2,4−トリアゾロ[4,3−a]ピリジン誘導体およびmGluR2受容体の正のアロステリック調節因子としてのその使用 |
RS53075B (en) | 2009-05-12 | 2014-04-30 | Janssen Pharmaceuticals Inc. | 1,2,4-TRIAZOLO [4,3-A] PYRIDINE DERIVATIVES AND THEIR USE IN THE TREATMENT OR PREVENTION OF NEUROLOGICAL AND PSYCHIATRIC DISORDERS |
MY153913A (en) | 2009-05-12 | 2015-04-15 | Janssen Pharmaceuticals Inc | 7-aryl-1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mglur2 receptors |
WO2011039528A1 (en) | 2009-10-02 | 2011-04-07 | Astrazeneca Ab | 2-pyridone compounds used as inhibitors of neutrophil elastase |
EP2643320B1 (en) | 2010-11-08 | 2015-03-04 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
EP2649069B1 (en) | 2010-11-08 | 2015-08-26 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
EP2661435B1 (en) | 2010-11-08 | 2015-08-19 | Janssen Pharmaceuticals, Inc. | 1,2,4-TRIAZOLO[4,3-a]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS |
BR112013016033A2 (pt) | 2010-12-23 | 2018-06-05 | Pfizer | moduladores do receptor de glucagon |
IL227559A (en) | 2011-02-08 | 2016-04-21 | Pfizer | Glucagon receptor modulator |
ES2543050T3 (es) | 2011-02-28 | 2015-08-14 | Array Biopharma, Inc. | Inhibidores de serina/treonina quinasa |
WO2013014569A1 (en) | 2011-07-22 | 2013-01-31 | Pfizer Inc. | Quinolinyl glucagon receptor modulators |
US9187462B2 (en) | 2011-08-04 | 2015-11-17 | Array Biopharma Inc. | Substituted quinazolines as serine/threonine kinase inhibitors |
CA2853024C (en) | 2011-11-11 | 2017-08-22 | Pfizer Inc. | 2-thiopyrimidinones |
CN103130787B (zh) * | 2011-11-24 | 2015-06-10 | 南开大学 | 嘧啶酮酰胺类化合物及其制备方法、抗hiv活性和抗tmv活性 |
SI2820009T1 (en) | 2012-03-01 | 2018-05-31 | Array Biopharma, Inc. | Serine / Threonine kinase inhibitors |
BR112015004548A2 (pt) | 2012-08-27 | 2017-08-08 | Array Biopharma Inc | inibidores de serina/treonina para tratamento de doenças hiperproliferativas |
JO3368B1 (ar) | 2013-06-04 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 6، 7- ثاني هيدرو بيرازولو [5،1-a] بيرازين- 4 (5 يد)- اون واستخدامها بصفة منظمات تفارغية سلبية لمستقبلات ميجلور 2 |
JO3367B1 (ar) | 2013-09-06 | 2019-03-13 | Janssen Pharmaceutica Nv | مركبات 2،1، 4- ثلاثي زولو [3،4-a] بيريدين واستخدامها بصفة منظمات تفارغية موجبة لمستقبلات ميجلور 2 |
ES2860298T3 (es) | 2014-01-21 | 2021-10-04 | Janssen Pharmaceutica Nv | Combinaciones que comprenden moduladores alostéricos positivos del receptor glutamatérgico metabotrópico de subtipo 2 y su uso |
DK3431106T3 (da) | 2014-01-21 | 2021-03-15 | Janssen Pharmaceutica Nv | Kombinationer omfattende positive allosteriske modulatorer eller orthosteriske agonister af metabotrop glutamaterg subtype 2-receptor og anvendelse af disse |
KR101693781B1 (ko) * | 2014-10-06 | 2017-01-09 | 한양대학교 에리카산학협력단 | 다이플루오로알킬기가 도입된 방향족 화합물의 제조 방법 |
EP3292109A1 (en) | 2015-05-05 | 2018-03-14 | Pfizer Inc | 2-thiopyrimidinones |
CN107200731B (zh) * | 2017-06-11 | 2020-10-23 | 湖南科技大学 | 一种含噻唑环吡啶酮衍生物及其制备方法和应用 |
JOP20220125A1 (ar) | 2019-11-25 | 2023-01-30 | Amgen Inc | مركبات حلقية غير متجانسة على هيئة مثبطات دلتا-5 ديساتوراز وطرق لاستخدامها |
CN115650906A (zh) * | 2022-11-04 | 2023-01-31 | 苏州艾缇克药物化学有限公司 | 一种2-氨基异烟酸的制备方法 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5620999A (en) * | 1994-07-28 | 1997-04-15 | Weier; Richard M. | Benzenesulfonamide subtituted imidazolyl compounds for the treatment of inflammation |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1271116B (de) * | 1965-05-04 | 1968-06-27 | Bayer Ag | Verfahren zur Herstellung von 4-Hydroxypyrimidinen |
JPS6163680A (ja) * | 1984-09-05 | 1986-04-01 | Kanto Ishi Pharma Co Ltd | ピリミド〔1,2−a〕ベンズイミダゾ−ル誘導体及びその製造方法 |
IL123950A (en) * | 1995-10-06 | 2001-04-30 | Merck & Co Inc | Transformed imidazoles with anti-cancer and cytokine-inhibiting activity and pharmaceutical preparations containing them |
WO1997016442A1 (en) * | 1995-10-31 | 1997-05-09 | Merck & Co., Inc. | Substituted pyridyl pyrroles, compositions containing such compounds and methods of use |
-
1997
- 1997-12-04 EP EP97951678A patent/EP0948496A2/en not_active Withdrawn
- 1997-12-04 KR KR10-1999-7005022A patent/KR100476586B1/ko not_active IP Right Cessation
- 1997-12-04 WO PCT/US1997/022949 patent/WO1998024780A2/en not_active Application Discontinuation
- 1997-12-04 JP JP52590298A patent/JP2002514196A/ja active Pending
- 1997-12-04 CZ CZ992016A patent/CZ9902016A3/cs unknown
- 1997-12-04 AU AU55254/98A patent/AU735901C/en not_active Ceased
- 1997-12-04 IL IL13018197A patent/IL130181A0/xx unknown
- 1997-12-04 CN CNB971815585A patent/CN1328277C/zh not_active Expired - Fee Related
- 1997-12-04 BR BR9713863-0A patent/BR9713863A/pt not_active Application Discontinuation
- 1997-12-04 CA CA002274093A patent/CA2274093C/en not_active Expired - Fee Related
- 1997-12-04 HU HU0001140A patent/HUP0001140A3/hu unknown
- 1997-12-04 NZ NZ335992A patent/NZ335992A/xx unknown
-
1999
- 1999-06-23 BG BG103521A patent/BG65129B1/bg unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5620999A (en) * | 1994-07-28 | 1997-04-15 | Weier; Richard M. | Benzenesulfonamide subtituted imidazolyl compounds for the treatment of inflammation |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110078674A (zh) * | 2019-04-10 | 2019-08-02 | 昆明理工大学 | 一种2-烃基胺基嘧啶酮的制备方法 |
CN110078674B (zh) * | 2019-04-10 | 2022-11-01 | 昆明理工大学 | 一种2-烃基胺基嘧啶酮的制备方法 |
Also Published As
Publication number | Publication date |
---|---|
AU5525498A (en) | 1998-06-29 |
IL130181A0 (en) | 2000-06-01 |
KR20000069329A (ko) | 2000-11-25 |
EP0948496A2 (en) | 1999-10-13 |
WO1998024780A3 (en) | 1998-07-30 |
HUP0001140A3 (en) | 2002-05-28 |
CZ9902016A3 (cs) | 1999-11-17 |
CN1246857A (zh) | 2000-03-08 |
KR100476586B1 (ko) | 2005-03-18 |
WO1998024780A2 (en) | 1998-06-11 |
AU735901B2 (en) | 2001-07-19 |
CA2274093A1 (en) | 1998-06-11 |
BG103521A (en) | 2000-07-31 |
NZ335992A (en) | 2001-09-28 |
BG65129B1 (bg) | 2007-03-30 |
JP2002514196A (ja) | 2002-05-14 |
HUP0001140A2 (hu) | 2001-04-28 |
BR9713863A (pt) | 2000-03-14 |
CA2274093C (en) | 2006-11-07 |
AU735901C (en) | 2004-02-12 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN1328277C (zh) | 取代的嘧啶酮和吡啶酮化合物和它们的应用 | |
US6420385B1 (en) | Substituted pyrimidinone and pyridone compounds and methods of use | |
JP5627574B2 (ja) | 炎症性および線維性疾患を治療するための化合物および方法 | |
JP6553236B2 (ja) | Cc9アンタゴニストとしてのピラゾール−1−イルベンゼンスルホンアミド | |
CN106467541B (zh) | 取代喹诺酮类衍生物或其药学上可接受的盐或立体异构体及其药用组合物和应用 | |
JP4533534B2 (ja) | グリコーゲンシンターゼキナーゼ3のインヒビター | |
RU2264403C2 (ru) | Замещенные 2-арил-3-(гетероарил) имидазо [1,2-а] пиримидины, содержащие их фармацевтические композиции и связанные с ними способы | |
US6610698B2 (en) | Substituted pyrimidine compounds and methods of use | |
CN112601750A (zh) | 用于治疗癌症的作为ptpn11(shp2)抑制剂的6-(4-氨基-3-甲基-2-氧杂-8-氮杂螺[4.5]癸烷-8-基)-3-(2,3-二氯苯基)-2-甲基嘧啶-4(3h)-酮衍生物及相关化合物 | |
KR20000057137A (ko) | 아릴 및 헤테로아릴로 치환된 융합 피롤 항염증제 | |
KR20020063934A (ko) | 코르티코트로핀 방출 인자 길항제 | |
PT1042293E (pt) | Compostos de piridazina e piridina substituídos e as suas utilizações farmacêuticas | |
EA010485B1 (ru) | Производное n,n'-дифенилмочевины, фармацевтическая композиция (варианты) и способ лечения и предупреждения заболеваний и состояний с его использованием (варианты) | |
CA2825367A1 (en) | Diarylacetylene hydrazide containing tyrosine kinase inhibitors | |
WO2008025526A1 (en) | Indole derivatives, their manufacture and use as pharmaceutical agents | |
US20050043301A1 (en) | Substituted heterocyclic compounds and methods of use | |
BG65128B1 (bg) | Заместени пирамидинови съединения и тяхното използване | |
SI21096A1 (sl) | Derivati karboksilne kisline, ki inhibirajo vezavo integrinov na njihove receptorje | |
AU8142901A (en) | Substituted pyrimidinone and pyridone compounds and methods of use | |
KR20000069328A (ko) | 치환된 피리미딘 화합물과 그것의 용도 | |
CA2234701A1 (en) | Substituted pyridyl pyrroles, compositions containing such compounds and methods of use | |
MXPA00006070A (en) | Substituted pyridine and pyridazine compounds and their pharmaceutical use |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
C19 | Lapse of patent right due to non-payment of the annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |