CA2622725A1

CA2622725A1 - 5-oxo-5,8-dihydro-pyrido-pyrimidines comme inhibiteurs de kinase c-fms

5-oxo-5,8-dihydro-pyrido-pyrimidines comme inhibiteurs de kinase c-fms Download PDF

Info

Publication number: CA2622725A1
Authority: CA; Canada
Prior art keywords: oxo; dihydro; pyrido; pyrimidine; carboxylic acid
Prior art date: 2005-09-14
Legal status : Abandoned

Application number

CA002622725A

Other languages

English (en)

Inventor

Mark R. Player

Hui Huang

Daniel Hutta

Current Assignee

Janssen Pharmaceutica NV

Original Assignee

Individual

Priority date

2005-09-14

Filing date

2006-09-13

Publication date

2007-03-22

2006-09-13 Application filed by Individual filed Critical Individual

2007-03-22 Publication of CA2622725A1 publication Critical patent/CA2622725A1/fr

Status Abandoned legal-status Critical Current

Links

108010058398 Macrophage Colony-Stimulating Factor Receptor Proteins 0.000 title claims abstract description 25
239000003112 inhibitor Substances 0.000 title abstract description 8
150000001875 compounds Chemical class 0.000 claims abstract description 229
125000000217 alkyl group Chemical group 0.000 claims description 130
-1 oxazolidinonyl Chemical group 0.000 claims description 117
238000000034 method Methods 0.000 claims description 100
229910052739 hydrogen Inorganic materials 0.000 claims description 84
239000001257 hydrogen Substances 0.000 claims description 83
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 63
150000002431 hydrogen Chemical class 0.000 claims description 41
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
125000004193 piperazinyl group Chemical group 0.000 claims description 28
125000000753 cycloalkyl group Chemical group 0.000 claims description 26
JLLYLQLDYORLBB-UHFFFAOYSA-N 5-bromo-n-methylthiophene-2-sulfonamide Chemical compound CNS(=O)(=O)C1=CC=C(Br)S1 JLLYLQLDYORLBB-UHFFFAOYSA-N 0.000 claims description 22
125000003545 alkoxy group Chemical group 0.000 claims description 22
229910052736 halogen Inorganic materials 0.000 claims description 22
150000002367 halogens Chemical class 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
125000003118 aryl group Chemical group 0.000 claims description 17
125000004663 dialkyl amino group Chemical group 0.000 claims description 17
125000001072 heteroaryl group Chemical group 0.000 claims description 17
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
241000124008 Mammalia Species 0.000 claims description 13
238000011282 treatment Methods 0.000 claims description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 11
102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 11
125000004350 aryl cycloalkyl group Chemical group 0.000 claims description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 11
125000003386 piperidinyl group Chemical group 0.000 claims description 10
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
206010028980 Neoplasm Diseases 0.000 claims description 8
125000002877 alkyl aryl group Chemical group 0.000 claims description 8
150000001602 bicycloalkyls Chemical group 0.000 claims description 8
125000004367 cycloalkylaryl group Chemical group 0.000 claims description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
230000002401 inhibitory effect Effects 0.000 claims description 8
206010039073 rheumatoid arthritis Diseases 0.000 claims description 8
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 7
XCJIUNJTUIGAPW-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 XCJIUNJTUIGAPW-UHFFFAOYSA-N 0.000 claims description 7
VGHHBKAKIRKWTD-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-[(dimethylamino)methyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)CC1=CC=CC(NC=2N=C3C(C(C(C(N)=O)=CN3C=3C=C4CCCC4=CC=3)=O)=CN=2)=C1 VGHHBKAKIRKWTD-UHFFFAOYSA-N 0.000 claims description 6
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
125000002757 morpholinyl group Chemical group 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
RZASZBXSWIEAKW-UHFFFAOYSA-N 1-(2,3-dihydro-1h-inden-5-yl)-7-[4-(4-methylpiperazin-1-yl)anilino]-4-oxo-1,6-naphthyridine-3-carboxamide Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC(N=C1)=CC2=C1C(=O)C(C(N)=O)=CN2C1=CC=C(CCC2)C2=C1 RZASZBXSWIEAKW-UHFFFAOYSA-N 0.000 claims description 5
SIQHZHFJFLIILX-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(3,5-dimethylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1C(C)NC(C)CN1C1=CC=CC(NC=2N=C3C(C(C(C(N)=O)=CN3C=3C=C4CCCC4=CC=3)=O)=CN=2)=C1 SIQHZHFJFLIILX-UHFFFAOYSA-N 0.000 claims description 5
WWRZVYXXKXIHBB-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(dimethylcarbamoyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C(=O)C1=CC=CC(NC=2N=C3C(C(C(C(N)=O)=CN3C=3C=C4CCCC4=CC=3)=O)=CN=2)=C1 WWRZVYXXKXIHBB-UHFFFAOYSA-N 0.000 claims description 5
RBTDSACAVFNZRD-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(dimethylcarbamoyl)anilino]-n-methyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=CC(C(=O)N(C)C)=C1 RBTDSACAVFNZRD-UHFFFAOYSA-N 0.000 claims description 5
REGDCIVYHAGXML-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(morpholin-4-ylmethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1CN1CCOCC1 REGDCIVYHAGXML-UHFFFAOYSA-N 0.000 claims description 5
HRPMKCIOVYRLPE-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-[(4-methylpiperazin-1-yl)methyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1CC1=CC=CC(NC=2N=C3C(C(C(C(N)=O)=CN3C=3C=C4CCCC4=CC=3)=O)=CN=2)=C1 HRPMKCIOVYRLPE-UHFFFAOYSA-N 0.000 claims description 5
OQVRIQHCXNVULE-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-[(dimethylamino)methyl]anilino]-n-methyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=CC(CN(C)C)=C1 OQVRIQHCXNVULE-UHFFFAOYSA-N 0.000 claims description 5
ATFIPDDKYWSEQD-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(2-morpholin-4-ylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCN1CCOCC1 ATFIPDDKYWSEQD-UHFFFAOYSA-N 0.000 claims description 5
JYURXLFYRONLAX-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(3,5-dimethylpiperazin-1-yl)anilino]-n-methyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CC(C)NC(C)C1 JYURXLFYRONLAX-UHFFFAOYSA-N 0.000 claims description 5
SHCFJIXSPWRTLY-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 SHCFJIXSPWRTLY-UHFFFAOYSA-N 0.000 claims description 5
AETAVEWUKKQITB-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(dimethylamino)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC(N(C)C)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 AETAVEWUKKQITB-UHFFFAOYSA-N 0.000 claims description 5
UHYNYWMDYRMSHH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(morpholin-4-ylmethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CN1CCOCC1 UHYNYWMDYRMSHH-UHFFFAOYSA-N 0.000 claims description 5
JVEIRUGXUUBLRS-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-(4-piperidin-4-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C1CCNCC1 JVEIRUGXUUBLRS-UHFFFAOYSA-N 0.000 claims description 5
SAGRWAKYPQJNMH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-5-oxo-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCNCC1 SAGRWAKYPQJNMH-UHFFFAOYSA-N 0.000 claims description 5
SNYPHRBZHRBBDZ-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 SNYPHRBZHRBBDZ-UHFFFAOYSA-N 0.000 claims description 5
AIARRPKAXFYSNP-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-5-oxo-2-[4-[2-(propan-2-ylsulfamoyl)ethyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(CCS(=O)(=O)NC(C)C)C=C1 AIARRPKAXFYSNP-UHFFFAOYSA-N 0.000 claims description 5
XHYOTOWYDSHSMF-UHFFFAOYSA-N 8-cyclohexyl-2-[3-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC(NC=2N=C3C(C(C(C(N)=O)=CN3C3CCCCC3)=O)=CN=2)=C1 XHYOTOWYDSHSMF-UHFFFAOYSA-N 0.000 claims description 5
MFLKWQNWTMHISF-UHFFFAOYSA-N 8-cyclohexyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C3CCCCC3)C2=N1 MFLKWQNWTMHISF-UHFFFAOYSA-N 0.000 claims description 5
108091000080 Phosphotransferase Proteins 0.000 claims description 5
125000003282 alkyl amino group Chemical group 0.000 claims description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
WFBYKPZOXWZWDH-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-(4-fluoroanilino)-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(F)C=C1 WFBYKPZOXWZWDH-UHFFFAOYSA-N 0.000 claims description 5
ITGKWZKYKMYMCE-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-(4-morpholin-4-ylanilino)-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCOCC1 ITGKWZKYKMYMCE-UHFFFAOYSA-N 0.000 claims description 5
KBWQDMYXLQAPSU-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(dimethylamino)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(N(C)C)C=C1 KBWQDMYXLQAPSU-UHFFFAOYSA-N 0.000 claims description 5
RKOGSOHQQAODSM-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCN(C)CC3)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 RKOGSOHQQAODSM-UHFFFAOYSA-N 0.000 claims description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
102000020233 phosphotransferase Human genes 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
RJKWGSGVGBDVKE-UHFFFAOYSA-N 2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxo-8-phenylpyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=CC=CC=3)C2=N1 RJKWGSGVGBDVKE-UHFFFAOYSA-N 0.000 claims description 4
SMCZPZKZVMUPAH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(3,5-dimethylpiperazin-1-yl)anilino]-n-methyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CC(C)NC(C)C1 SMCZPZKZVMUPAH-UHFFFAOYSA-N 0.000 claims description 4
QKVQYFBPYPVUJZ-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(dimethylamino)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound CN(C)C1=CC=CC(NC=2N=C3C(C(C(C(N)=O)=CN3C=3C=C4CCCC4=CC=3)=O)=CN=2)=C1 QKVQYFBPYPVUJZ-UHFFFAOYSA-N 0.000 claims description 4
SKFYHVMWDPZGFP-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C(=O)CN(C)C)CCC1C1=CC=CC(NC=2N=C3C(C(C(C(N)=O)=CN3C=3C=C4CCCC4=CC=3)=O)=CN=2)=C1 SKFYHVMWDPZGFP-UHFFFAOYSA-N 0.000 claims description 4
AHBSXTVFKVCNCE-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(3,5-dimethylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1C(C)NC(C)CN1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 AHBSXTVFKVCNCE-UHFFFAOYSA-N 0.000 claims description 4
HFAGIUAHTBLSBD-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(3,5-dimethylpiperazin-1-yl)anilino]-n-ethyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CC(C)NC(C)C1 HFAGIUAHTBLSBD-UHFFFAOYSA-N 0.000 claims description 4
JRYPTUMSBBTJMS-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(O)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 JRYPTUMSBBTJMS-UHFFFAOYSA-N 0.000 claims description 4
IWPVUHHCWGVPNJ-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[(4-methylpiperazin-1-yl)methyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1CC(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 IWPVUHHCWGVPNJ-UHFFFAOYSA-N 0.000 claims description 4
ARAIYZSXPMUTPV-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[3-(dimethylamino)-2-hydroxypropoxy]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC(OCC(O)CN(C)C)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 ARAIYZSXPMUTPV-UHFFFAOYSA-N 0.000 claims description 4
AQRGYZFIHTVAAL-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[3-(dimethylamino)-2-hydroxypropoxy]anilino]-n-ethyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(OCC(O)CN(C)C)C=C1 AQRGYZFIHTVAAL-UHFFFAOYSA-N 0.000 claims description 4
ZDSBDOSRUAGKIO-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-(3-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CCNCC1 ZDSBDOSRUAGKIO-UHFFFAOYSA-N 0.000 claims description 4
KQKRVYHUGXKQRH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCNCC1 KQKRVYHUGXKQRH-UHFFFAOYSA-N 0.000 claims description 4
DIRBIECYJJFHJQ-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-2-[4-(2-morpholin-4-ylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCN1CCOCC1 DIRBIECYJJFHJQ-UHFFFAOYSA-N 0.000 claims description 4
NKVOKKOMBNOQAR-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 NKVOKKOMBNOQAR-UHFFFAOYSA-N 0.000 claims description 4
VETWSCYIJAHHGR-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-5-oxo-2-(4-piperidin-4-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C1CCNCC1 VETWSCYIJAHHGR-UHFFFAOYSA-N 0.000 claims description 4
UDESKBQLSTXTBP-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-2-[4-(2-morpholin-4-ylsulfonylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCS(=O)(=O)N1CCOCC1 UDESKBQLSTXTBP-UHFFFAOYSA-N 0.000 claims description 4
NBKLIVZCUPZPQK-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-5-oxo-2-(3-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CCNCC1 NBKLIVZCUPZPQK-UHFFFAOYSA-N 0.000 claims description 4
DJYMIBUSNWTGTQ-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-5-oxo-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCNCC1 DJYMIBUSNWTGTQ-UHFFFAOYSA-N 0.000 claims description 4
RZUCEFAFHFOZJN-UHFFFAOYSA-N 8-(3-bicyclo[2.2.1]heptanyl)-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C3C4CCC(C4)C3)C2=N1 RZUCEFAFHFOZJN-UHFFFAOYSA-N 0.000 claims description 4
FLQZGCAMRQBGSK-UHFFFAOYSA-N 8-cyclohexyl-2-[4-(2-morpholin-4-ylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=CC(CCN4CCOCC4)=CC=3)=NC=C2C(=O)C(C(=O)N)=CN1C1CCCCC1 FLQZGCAMRQBGSK-UHFFFAOYSA-N 0.000 claims description 4
VDDADWSSSIOZGY-UHFFFAOYSA-N 8-cyclohexyl-2-[4-(2-morpholin-4-ylsulfonylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=CC(CCS(=O)(=O)N4CCOCC4)=CC=3)=NC=C2C(=O)C(C(=O)N)=CN1C1CCCCC1 VDDADWSSSIOZGY-UHFFFAOYSA-N 0.000 claims description 4
SPGYUVDBYSZXFR-UHFFFAOYSA-N 8-cyclohexyl-5-oxo-2-[4-[2-(propan-2-ylsulfamoyl)ethyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC(CCS(=O)(=O)NC(C)C)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C3CCCCC3)C2=N1 SPGYUVDBYSZXFR-UHFFFAOYSA-N 0.000 claims description 4
WHBVVZPDEFKMLP-UHFFFAOYSA-N 8-cyclopentyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C3CCCC3)C2=N1 WHBVVZPDEFKMLP-UHFFFAOYSA-N 0.000 claims description 4
206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
206010007572 Cardiac hypertrophy Diseases 0.000 claims description 4
208000006029 Cardiomegaly Diseases 0.000 claims description 4
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
230000000694 effects Effects 0.000 claims description 4
YZROMTIEYINDOE-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(dimethylamino)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=CC(N(C)C)=C1 YZROMTIEYINDOE-UHFFFAOYSA-N 0.000 claims description 4
WYVYXWFVQWEMDO-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-(4-morpholin-4-ylanilino)-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCOCC1 WYVYXWFVQWEMDO-UHFFFAOYSA-N 0.000 claims description 3
BWFZLXWRZDSPHK-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[2-hydroxy-4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1C(C=C1O)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 BWFZLXWRZDSPHK-UHFFFAOYSA-N 0.000 claims description 3
QYLZFFVSZPHIMA-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1C1=CC=CC(NC=2N=C3C(C(C(C(N)=O)=CN3C=3C=C4CCCC4=CC=3)=O)=CN=2)=C1 QYLZFFVSZPHIMA-UHFFFAOYSA-N 0.000 claims description 3
TXOCGJLQJJWNPH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(dimethylcarbamoyl)anilino]-n-ethyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=CC(C(=O)N(C)C)=C1 TXOCGJLQJJWNPH-UHFFFAOYSA-N 0.000 claims description 3
WHMDFEPAUJEUHG-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(hydroxymethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=CC(CO)=C1 WHMDFEPAUJEUHG-UHFFFAOYSA-N 0.000 claims description 3
KGBTXYSTHPOTKV-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-[1-[2-(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1CC(=O)N1CCC(C=2C=C(NC=3N=C4C(C(C(C(N)=O)=CN4C=4C=C5CCCC5=CC=4)=O)=CN=3)C=CC=2)CC1 KGBTXYSTHPOTKV-UHFFFAOYSA-N 0.000 claims description 3
WQGUJEFNLUBLCH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[(dimethylamino)methyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=CC(CN(C)C)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 WQGUJEFNLUBLCH-UHFFFAOYSA-N 0.000 claims description 3
HTKSYAZYYJWSEF-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C(=O)CN(C)C)CCC1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 HTKSYAZYYJWSEF-UHFFFAOYSA-N 0.000 claims description 3
MOYHXRQYKQAYCL-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[3-(dimethylamino)-2-hydroxypropoxy]anilino]-n-methyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(OCC(O)CN(C)C)C=C1 MOYHXRQYKQAYCL-UHFFFAOYSA-N 0.000 claims description 3
ZCNMCRNFQSNOPD-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-(4-pyrazol-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1C=CC=N1 ZCNMCRNFQSNOPD-UHFFFAOYSA-N 0.000 claims description 3
BEDUDWXZVLGZTN-IBGZPJMESA-N 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-[4-[[(4s)-2-oxo-1,3-oxazolidin-4-yl]methyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)N)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C[C@H]1COC(=O)N1 BEDUDWXZVLGZTN-IBGZPJMESA-N 0.000 claims description 3
OXBFRVOGASXKBH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-2-[3-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CCN(C)CC1 OXBFRVOGASXKBH-UHFFFAOYSA-N 0.000 claims description 3
IXHJCUXDKKXMGP-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-2-[4-[(4-methylpiperazin-1-yl)methyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CN1CCN(C)CC1 IXHJCUXDKKXMGP-UHFFFAOYSA-N 0.000 claims description 3
XNGDGDIHSVOJPB-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-2-[4-[2-(4-methylpiperazin-1-yl)ethyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCN1CCN(C)CC1 XNGDGDIHSVOJPB-UHFFFAOYSA-N 0.000 claims description 3
BEVVJWZPWXBPBH-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-5-oxo-2-(3-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CCNCC1 BEVVJWZPWXBPBH-UHFFFAOYSA-N 0.000 claims description 3
DNZCSZPFEKXOKV-NRFANRHFSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-5-oxo-2-[4-[[(4s)-2-oxo-1,3-oxazolidin-4-yl]methyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C[C@H]1COC(=O)N1 DNZCSZPFEKXOKV-NRFANRHFSA-N 0.000 claims description 3
NUEBFASKVIDNSK-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-2-[4-(2-morpholin-4-ylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCN1CCOCC1 NUEBFASKVIDNSK-UHFFFAOYSA-N 0.000 claims description 3
WSGGTOJSAKUDAJ-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-2-[4-[2-(4-methylpiperazin-1-yl)ethyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCN1CCN(C)CC1 WSGGTOJSAKUDAJ-UHFFFAOYSA-N 0.000 claims description 3
DPGIUCCJRKDYBK-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-5-oxo-2-(4-piperidin-4-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C1CCNCC1 DPGIUCCJRKDYBK-UHFFFAOYSA-N 0.000 claims description 3
GRYAXXJVCVQDLT-UHFFFAOYSA-N 8-benzyl-n-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCN(C)CC3)=NC=C2C(=O)C(C(=O)NC)=CN1CC1=CC=CC=C1 GRYAXXJVCVQDLT-UHFFFAOYSA-N 0.000 claims description 3
HZXHFRYFFYOZNP-UHFFFAOYSA-N 8-cyclohexyl-n-ethyl-2-[3-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=C(C=CC=3)N3CCN(C)CC3)=NC=C2C(=O)C(C(=O)NCC)=CN1C1CCCCC1 HZXHFRYFFYOZNP-UHFFFAOYSA-N 0.000 claims description 3
RYQHDZYCYMYIQT-UHFFFAOYSA-N 8-cyclohexyl-n-ethyl-2-[4-(2-morpholin-4-ylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=CC(CCN4CCOCC4)=CC=3)=NC=C2C(=O)C(C(=O)NCC)=CN1C1CCCCC1 RYQHDZYCYMYIQT-UHFFFAOYSA-N 0.000 claims description 3
ZOPIDYBVSLYDFA-UHFFFAOYSA-N 8-cyclohexyl-n-methyl-2-[3-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=C(C=CC=3)N3CCN(C)CC3)=NC=C2C(=O)C(C(=O)NC)=CN1C1CCCCC1 ZOPIDYBVSLYDFA-UHFFFAOYSA-N 0.000 claims description 3
201000001320 Atherosclerosis Diseases 0.000 claims description 3
208000007342 Diabetic Nephropathies Diseases 0.000 claims description 3
206010052779 Transplant rejections Diseases 0.000 claims description 3
208000033679 diabetic kidney disease Diseases 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
PRWYMOXZYHGMEJ-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[3-(dimethylamino)-2-hydroxypropoxy]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(OCC(O)CN(C)C)C=C1 PRWYMOXZYHGMEJ-UHFFFAOYSA-N 0.000 claims description 3
YORXTXBUWZXFEU-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-[4-(dimethylamino)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(NC=3C=CC(=CC=3)N(C)C)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 YORXTXBUWZXFEU-UHFFFAOYSA-N 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 3
CPBJKZGBWWZSFE-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-[(dimethylamino)methyl]anilino]-n-ethyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=CC(CN(C)C)=C1 CPBJKZGBWWZSFE-UHFFFAOYSA-N 0.000 claims description 2
UQIYZJHTIADSJK-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[1-[2-(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1CC(=O)N1CCC(C=2C=CC(NC=3N=C4C(C(C(C(N)=O)=CN4C=4C=C5CCCC5=CC=4)=O)=CN=3)=CC=2)CC1 UQIYZJHTIADSJK-UHFFFAOYSA-N 0.000 claims description 2
XTXKMZAHFLAVMY-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-2-[4-(2-morpholin-4-ylsulfonylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCS(=O)(=O)N1CCOCC1 XTXKMZAHFLAVMY-UHFFFAOYSA-N 0.000 claims description 2
PUXCKMVWJDGFFB-UHFFFAOYSA-N 8-(3-bicyclo[2.2.1]heptanyl)-n-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C3C4CCC(C4)C3)C2=NC=1NC(C=C1)=CC=C1N1CCN(C)CC1 PUXCKMVWJDGFFB-UHFFFAOYSA-N 0.000 claims description 2
KZRFMJRVJJHWAS-UHFFFAOYSA-N 8-cyclohexyl-2-[4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C(=O)CN(C)C)CCC1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C3CCCCC3)C2=N1 KZRFMJRVJJHWAS-UHFFFAOYSA-N 0.000 claims description 2
VGSUOFPXIAUMPW-UHFFFAOYSA-N 8-cyclohexyl-n-ethyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCN(C)CC3)=NC=C2C(=O)C(C(=O)NCC)=CN1C1CCCCC1 VGSUOFPXIAUMPW-UHFFFAOYSA-N 0.000 claims description 2
JBCNXFAGMUTEPX-UHFFFAOYSA-N 8-cyclohexyl-n-methyl-2-[4-(2-morpholin-4-ylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=CC(CCN4CCOCC4)=CC=3)=NC=C2C(=O)C(C(=O)NC)=CN1C1CCCCC1 JBCNXFAGMUTEPX-UHFFFAOYSA-N 0.000 claims description 2
SXIAGAZLVCKMTF-UHFFFAOYSA-N 8-cyclohexyl-n-methyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCN(C)CC3)=NC=C2C(=O)C(C(=O)NC)=CN1C1CCCCC1 SXIAGAZLVCKMTF-UHFFFAOYSA-N 0.000 claims description 2
208000024827 Alzheimer disease Diseases 0.000 claims description 2
208000024172 Cardiovascular disease Diseases 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
206010018364 Glomerulonephritis Diseases 0.000 claims description 2
206010061218 Inflammation Diseases 0.000 claims description 2
201000004681 Psoriasis Diseases 0.000 claims description 2
125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 claims description 2
230000033115 angiogenesis Effects 0.000 claims description 2
201000011510 cancer Diseases 0.000 claims description 2
206010012601 diabetes mellitus Diseases 0.000 claims description 2
229910052731 fluorine Inorganic materials 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
230000004054 inflammatory process Effects 0.000 claims description 2
208000037803 restenosis Diseases 0.000 claims description 2
201000000980 schizophrenia Diseases 0.000 claims description 2
KLHJDCUHOKZNOP-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[2-(4-methylpiperazin-1-yl)ethyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1CN(C)CCN1CCC(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(N)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 KLHJDCUHOKZNOP-UHFFFAOYSA-N 0.000 claims 2
LJCIQUXUHLPCNB-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-2-[3-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CCN(C)CC1 LJCIQUXUHLPCNB-UHFFFAOYSA-N 0.000 claims 2
239000002552 dosage form Substances 0.000 claims 2
IIDYFWVPVOGKFA-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-ethyl-5-oxo-2-[4-[2-(propan-2-ylsulfamoyl)ethyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(CCS(=O)(=O)NC(C)C)C=C1 IIDYFWVPVOGKFA-UHFFFAOYSA-N 0.000 claims 1
RQCZGCSYUKSJOG-FQEVSTJZSA-N 8-(2,3-dihydro-1h-inden-5-yl)-n-methyl-5-oxo-2-[4-[[(4s)-2-oxo-1,3-oxazolidin-4-yl]methyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N=1C=C2C(=O)C(C(=O)NC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C[C@H]1COC(=O)N1 RQCZGCSYUKSJOG-FQEVSTJZSA-N 0.000 claims 1
208000037408 Device failure Diseases 0.000 claims 1
208000031886 HIV Infections Diseases 0.000 claims 1
208000037357 HIV infectious disease Diseases 0.000 claims 1
208000022559 Inflammatory bowel disease Diseases 0.000 claims 1
208000011623 Obstructive Lung disease Diseases 0.000 claims 1
206010033645 Pancreatitis Diseases 0.000 claims 1
208000037099 Prosthesis Failure Diseases 0.000 claims 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims 1
201000000306 sarcoidosis Diseases 0.000 claims 1
150000003839 salts Chemical class 0.000 abstract description 17
230000003389 potentiating effect Effects 0.000 abstract description 5
239000012453 solvate Substances 0.000 abstract description 5
239000005483 tyrosine kinase inhibitor Substances 0.000 abstract description 5
239000000243 solution Substances 0.000 description 155
101150041968 CDC13 gene Proteins 0.000 description 127
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 127
239000007787 solid Substances 0.000 description 112
229910001868 water Inorganic materials 0.000 description 104
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 103
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 98
238000004895 liquid chromatography mass spectrometry Methods 0.000 description 91
238000001819 mass spectrum Methods 0.000 description 88
239000000203 mixture Substances 0.000 description 84
238000005160 1H NMR spectroscopy Methods 0.000 description 80
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 72
238000002953 preparative HPLC Methods 0.000 description 66
238000005481 NMR spectroscopy Methods 0.000 description 58
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 53
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 53
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 51
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
238000000746 purification Methods 0.000 description 44
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 42
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 34
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
239000002904 solvent Substances 0.000 description 32
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 31
239000011541 reaction mixture Substances 0.000 description 31
239000012044 organic layer Substances 0.000 description 28
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
MGJXBDMLVWIYOQ-UHFFFAOYSA-N methylazanide Chemical compound [NH-]C MGJXBDMLVWIYOQ-UHFFFAOYSA-N 0.000 description 26
SMQGGKGHDMQKKG-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-methylsulfonyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(S(C)(=O)=O)=NC=C2C(=O)C(C(=O)OCC)=CN1C1=CC=C(CCC2)C2=C1 SMQGGKGHDMQKKG-UHFFFAOYSA-N 0.000 description 24
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 21
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 20
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 19
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
229910052938 sodium sulfate Inorganic materials 0.000 description 18
235000011152 sodium sulphate Nutrition 0.000 description 18
229910052757 nitrogen Inorganic materials 0.000 description 17
DWZJQILNXRNMEZ-UHFFFAOYSA-N 5,8-dihydropyrido[2,3-d]pyrimidine-6-carboxylic acid Chemical compound N1=CN=CC2=C1NC=C(C2)C(=O)O DWZJQILNXRNMEZ-UHFFFAOYSA-N 0.000 description 16
229910052943 magnesium sulfate Inorganic materials 0.000 description 16
235000019341 magnesium sulphate Nutrition 0.000 description 16
239000000047 product Substances 0.000 description 16
239000000377 silicon dioxide Substances 0.000 description 16
QNTJNRVUVPHJST-UHFFFAOYSA-N 5-oxo-8h-pyrido[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1=NC=C2C(=O)C(C(=O)O)=CNC2=N1 QNTJNRVUVPHJST-UHFFFAOYSA-N 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
238000004587 chromatography analysis Methods 0.000 description 15
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 14
229910021529 ammonia Inorganic materials 0.000 description 14
239000012267 brine Substances 0.000 description 14
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 14
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
238000005984 hydrogenation reaction Methods 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 12
102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 11
108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 11
239000007832 Na2SO4 Substances 0.000 description 11
229910000027 potassium carbonate Inorganic materials 0.000 description 11
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 10
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
239000012131 assay buffer Substances 0.000 description 9
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 9
125000001424 substituent group Chemical group 0.000 description 9
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
150000001412 amines Chemical class 0.000 description 8
238000001816 cooling Methods 0.000 description 8
ZDFBTSUPBGYGEE-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-methylsulfonyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(S(C)(=O)=O)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 ZDFBTSUPBGYGEE-UHFFFAOYSA-N 0.000 description 8
125000005842 heteroatom Chemical group 0.000 description 8
210000002540 macrophage Anatomy 0.000 description 8
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 7
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 7
239000002253 acid Substances 0.000 description 7
235000011114 ammonium hydroxide Nutrition 0.000 description 7
150000001448 anilines Chemical class 0.000 description 7
YMWUJEATGCHHMB-DICFDUPASA-N dichloromethane-d2 Chemical compound [2H]C([2H])(Cl)Cl YMWUJEATGCHHMB-DICFDUPASA-N 0.000 description 7
DWRWSNAREGLUHZ-UHFFFAOYSA-N ethyl pyrimidine-4-carboxylate Chemical compound CCOC(=O)C1=CC=NC=N1 DWRWSNAREGLUHZ-UHFFFAOYSA-N 0.000 description 7
238000002875 fluorescence polarization Methods 0.000 description 7
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 7
239000013641 positive control Substances 0.000 description 7
MOZNZNKHRXRLLF-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=C(N)C=C1 MOZNZNKHRXRLLF-UHFFFAOYSA-N 0.000 description 6
102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
125000004429 atom Chemical group 0.000 description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
125000004432 carbon atom Chemical group C* 0.000 description 6
125000004122 cyclic group Chemical group 0.000 description 6
229960001484 edetic acid Drugs 0.000 description 6
150000002148 esters Chemical group 0.000 description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 6
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 5
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
108060008682 Tumor Necrosis Factor Proteins 0.000 description 5
125000003277 amino group Chemical group 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
238000003556 assay Methods 0.000 description 5
239000002585 base Substances 0.000 description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
230000003197 catalytic effect Effects 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
229940079593 drug Drugs 0.000 description 5
SNNHLSHDDGJVDM-UHFFFAOYSA-N ethyl 4-chloro-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1Cl SNNHLSHDDGJVDM-UHFFFAOYSA-N 0.000 description 5
230000005764 inhibitory process Effects 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
150000003254 radicals Chemical class 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
239000011734 sodium Substances 0.000 description 5
238000003756 stirring Methods 0.000 description 5
229910052717 sulfur Inorganic materials 0.000 description 5
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
102000003390 tumor necrosis factor Human genes 0.000 description 5
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
102000000589 Interleukin-1 Human genes 0.000 description 4
108010002352 Interleukin-1 Proteins 0.000 description 4
101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
150000001721 carbon Chemical group 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
201000010099 disease Diseases 0.000 description 4
ZCLGVXACCAZJOX-UHFFFAOYSA-N ethyl 3-chloropropanoate Chemical compound CCOC(=O)CCCl ZCLGVXACCAZJOX-UHFFFAOYSA-N 0.000 description 4
KUDNVLHRMLGRIL-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(3,5-dimethylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CC(C)NC(C)C1 KUDNVLHRMLGRIL-UHFFFAOYSA-N 0.000 description 4
HEZCGTYFHGPFKI-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C1CCN(C(=O)CN(C)C)CC1 HEZCGTYFHGPFKI-UHFFFAOYSA-N 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 4
239000013642 negative control Substances 0.000 description 4
239000012188 paraffin wax Substances 0.000 description 4
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
125000004434 sulfur atom Chemical group 0.000 description 4
239000000725 suspension Substances 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 4
WMASLRCNNKMRFP-UHFFFAOYSA-N 1-fluoro-3-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC(F)=C1 WMASLRCNNKMRFP-UHFFFAOYSA-N 0.000 description 3
WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 3
RJGHJWKQCJAJEP-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)aniline Chemical compound C1CN(C)CCN1C1=CC=CC(N)=C1 RJGHJWKQCJAJEP-UHFFFAOYSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
WYKQFHIPSPVIGN-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-methylsulfonyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound C1=C2CCCC2=CC(N2C=3C(C(C(C(N)=O)=C2)=O)=CN=C(N=3)S(=O)(=O)C)=C1 WYKQFHIPSPVIGN-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
239000007995 HEPES buffer Substances 0.000 description 3
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 3
101100221809 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cpd-7 gene Proteins 0.000 description 3
229920001213 Polysorbate 20 Polymers 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
230000035578 autophosphorylation Effects 0.000 description 3
125000002619 bicyclic group Chemical group 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
229910052791 calcium Inorganic materials 0.000 description 3
239000011575 calcium Substances 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
230000000875 corresponding effect Effects 0.000 description 3
150000002085 enols Chemical class 0.000 description 3
SCALPGTZZLHKLH-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CCN(C)CC1 SCALPGTZZLHKLH-UHFFFAOYSA-N 0.000 description 3
SFZQPYHVQDWFOE-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(dimethylcarbamoyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=CC(C(=O)N(C)C)=C1 SFZQPYHVQDWFOE-UHFFFAOYSA-N 0.000 description 3
PTWBBNQZQJZXPW-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[(4-methylpiperazin-1-yl)methyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CN1CCN(C)CC1 PTWBBNQZQJZXPW-UHFFFAOYSA-N 0.000 description 3
RZEBOULQTMMMRA-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-(3-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CCNCC1 RZEBOULQTMMMRA-UHFFFAOYSA-N 0.000 description 3
IZKZTGCZLUPGOL-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-[3-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(NC=3C=C(C=CC=3)N3CCN(C)CC3)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 IZKZTGCZLUPGOL-UHFFFAOYSA-N 0.000 description 3
125000000468 ketone group Chemical group 0.000 description 3
125000005647 linker group Chemical group 0.000 description 3
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
125000004433 nitrogen atom Chemical group N* 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
108090000765 processed proteins & peptides Proteins 0.000 description 3
239000000651 prodrug Chemical group 0.000 description 3
229940002612 prodrug Drugs 0.000 description 3
KLDGHPMEPAPPFX-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine-6-carboxamide Chemical compound N1=CN=CC2=CC(C(=O)N)=CN=C21 KLDGHPMEPAPPFX-UHFFFAOYSA-N 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 3
235000010265 sodium sulphite Nutrition 0.000 description 3
241000894007 species Species 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
239000000126 substance Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
XYHFIZFIVZIEBS-UHFFFAOYSA-N tert-butyl n-(3-piperidin-4-ylphenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CC(C2CCNCC2)=C1 XYHFIZFIVZIEBS-UHFFFAOYSA-N 0.000 description 3
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 2
YJXVSUZCKDNHCV-UHFFFAOYSA-N 1-[4-(4-aminophenyl)piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C1CN(C(=O)CN(C)C)CCC1C1=CC=C(N)C=C1 YJXVSUZCKDNHCV-UHFFFAOYSA-N 0.000 description 2
JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 description 2
IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical compound CC1CNCC(C)N1 IFNWESYYDINUHV-UHFFFAOYSA-N 0.000 description 2
FKWXDMXNNHJGRP-UHFFFAOYSA-N 2-(4-aminophenyl)-n-propan-2-ylethanesulfonamide Chemical compound CC(C)NS(=O)(=O)CCC1=CC=C(N)C=C1 FKWXDMXNNHJGRP-UHFFFAOYSA-N 0.000 description 2
MDYDGUOQFUQOGE-UHFFFAOYSA-N 2-methylpropanethioic acid S-[7-oxo-7-[(4-phenyl-2-thiazolyl)amino]heptyl] ester Chemical compound S1C(NC(=O)CCCCCCSC(=O)C(C)C)=NC(C=2C=CC=CC=2)=C1 MDYDGUOQFUQOGE-UHFFFAOYSA-N 0.000 description 2
YFDOOCHJXUBKOU-UHFFFAOYSA-N 2-methylsulfanyl-5-oxo-8-phenyl-6,7-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile Chemical compound C12=NC(SC)=NC=C2C(=O)C(C#N)CN1C1=CC=CC=C1 YFDOOCHJXUBKOU-UHFFFAOYSA-N 0.000 description 2
BUTSJLQVLQWKQW-UHFFFAOYSA-N 2-methylsulfanyl-5-oxo-8-phenylpyrido[2,3-d]pyrimidine-6-carbonitrile Chemical compound N=1C(SC)=NC=C(C(C(C#N)=C2)=O)C=1N2C1=CC=CC=C1 BUTSJLQVLQWKQW-UHFFFAOYSA-N 0.000 description 2
CNQZPDKTCNNPRA-UHFFFAOYSA-N 2-methylsulfonyl-5-oxo-8-phenylpyrido[2,3-d]pyrimidine-6-carbonitrile Chemical compound N=1C(S(=O)(=O)C)=NC=C(C(C(C#N)=C2)=O)C=1N2C1=CC=CC=C1 CNQZPDKTCNNPRA-UHFFFAOYSA-N 0.000 description 2
MINISYQOVCONSD-UHFFFAOYSA-N 4-(2-morpholin-4-ylsulfonylethyl)aniline Chemical compound C1=CC(N)=CC=C1CCS(=O)(=O)N1CCOCC1 MINISYQOVCONSD-UHFFFAOYSA-N 0.000 description 2
FPBFBURPCHKEKH-UHFFFAOYSA-N 4-(3,5-dimethylpiperazin-1-yl)aniline Chemical compound C1C(C)NC(C)CN1C1=CC=C(N)C=C1 FPBFBURPCHKEKH-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical group OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
101000916644 Homo sapiens Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
229910002651 NO3 Inorganic materials 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
MKNSDBXBVYGQOY-UHFFFAOYSA-N OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1N(C(=O)CN(C)C)CCCC1C1=CC=C(N)C=C1 Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1N(C(=O)CN(C)C)CCCC1C1=CC=C(N)C=C1 MKNSDBXBVYGQOY-UHFFFAOYSA-N 0.000 description 2
208000008589 Obesity Diseases 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
238000006069 Suzuki reaction reaction Methods 0.000 description 2
YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
235000011054 acetic acid Nutrition 0.000 description 2
229910052783 alkali metal Inorganic materials 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
125000003710 aryl alkyl group Chemical group 0.000 description 2
229940077388 benzenesulfonate Drugs 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
ZSANYRMTSBBUCA-UHFFFAOYSA-N diethyl 3-oxopentanedioate Chemical compound CCOC(=O)CC(=O)CC(=O)OCC ZSANYRMTSBBUCA-UHFFFAOYSA-N 0.000 description 2
239000013024 dilution buffer Substances 0.000 description 2
229960001760 dimethyl sulfoxide Drugs 0.000 description 2
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 description 2
JBQWMZMMLLZXDG-UHFFFAOYSA-N ethyl 3-(2,3-dihydro-1h-inden-5-ylamino)propanoate Chemical compound CCOC(=O)CCNC1=CC=C2CCCC2=C1 JBQWMZMMLLZXDG-UHFFFAOYSA-N 0.000 description 2
AAUBVINEXCCXOK-UHFFFAOYSA-N ethyl 4,6-dichloropyridine-3-carboxylate Chemical compound CCOC(=O)C1=CN=C(Cl)C=C1Cl AAUBVINEXCCXOK-UHFFFAOYSA-N 0.000 description 2
ABWZVMMLJAFQTL-UHFFFAOYSA-N ethyl 4-[benzyl-(3-ethoxy-3-oxopropyl)amino]-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound N=1C(SC)=NC=C(C(=O)OCC)C=1N(CCC(=O)OCC)CC1=CC=CC=C1 ABWZVMMLJAFQTL-UHFFFAOYSA-N 0.000 description 2
OKLKCLDQBBCNAY-UHFFFAOYSA-N ethyl 4-[n-(2-cyanoethyl)anilino]-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=CN=C(SC)N=C1N(CCC#N)C1=CC=CC=C1 OKLKCLDQBBCNAY-UHFFFAOYSA-N 0.000 description 2
KEIYBNKRWZOZOD-UHFFFAOYSA-N ethyl 6-chloro-4-[2,3-dihydro-1h-inden-5-yl-(3-ethoxy-3-oxopropyl)amino]pyridine-3-carboxylate Chemical compound C=1C=C2CCCC2=CC=1N(CCC(=O)OCC)C1=CC(Cl)=NC=C1C(=O)OCC KEIYBNKRWZOZOD-UHFFFAOYSA-N 0.000 description 2
YIOCMDQNCVDCNG-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-(3,5-dimethylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=1)=CC=CC=1N1CC(C)NC(C)C1 YIOCMDQNCVDCNG-UHFFFAOYSA-N 0.000 description 2
OWCZJNHOMAMEPQ-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(2-morpholin-4-ylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCN1CCOCC1 OWCZJNHOMAMEPQ-UHFFFAOYSA-N 0.000 description 2
OJVXKJDGCCKOMG-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[(dimethylamino)methyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(CN(C)C)C=C1 OJVXKJDGCCKOMG-UHFFFAOYSA-N 0.000 description 2
SJIWMSFEFGFDBB-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[2-(4-methylpiperazin-1-yl)ethyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCN1CCN(C)CC1 SJIWMSFEFGFDBB-UHFFFAOYSA-N 0.000 description 2
CJXGUMUKIJNPID-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-(4-piperazin-1-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1N1CCNCC1 CJXGUMUKIJNPID-UHFFFAOYSA-N 0.000 description 2
DKZXFOWWBBHIJS-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-[4-[2-(propan-2-ylsulfamoyl)ethyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=C(CCS(=O)(=O)NC(C)C)C=C1 DKZXFOWWBBHIJS-UHFFFAOYSA-N 0.000 description 2
FYHSAZCXKANNFR-UHFFFAOYSA-N ethyl 8-benzyl-2-methylsulfanyl-5-oxo-6,7-dihydropyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(SC)=NC=C2C(=O)C(C(=O)OCC)CN1CC1=CC=CC=C1 FYHSAZCXKANNFR-UHFFFAOYSA-N 0.000 description 2
YVTDXTMQGGUDCP-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-[4-(2-morpholin-4-ylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(NC=3C=CC(CCN4CCOCC4)=CC=3)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 YVTDXTMQGGUDCP-UHFFFAOYSA-N 0.000 description 2
LLVGJUIIGUANQZ-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-[4-(2-morpholin-4-ylsulfonylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(NC=3C=CC(CCS(=O)(=O)N4CCOCC4)=CC=3)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 LLVGJUIIGUANQZ-UHFFFAOYSA-N 0.000 description 2
ZFXNTVYRPUVTCI-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-[4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(NC=3C=CC(=CC=3)C3CCN(CC3)C(=O)CN(C)C)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 ZFXNTVYRPUVTCI-UHFFFAOYSA-N 0.000 description 2
QGNWECUOLPNEBK-UHFFFAOYSA-N ethyl 8-cyclohexyl-5-oxo-2-[4-[2-(propan-2-ylsulfamoyl)ethyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(NC=3C=CC(CCS(=O)(=O)NC(C)C)=CC=3)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 QGNWECUOLPNEBK-UHFFFAOYSA-N 0.000 description 2
125000004494 ethyl ester group Chemical group 0.000 description 2
230000005284 excitation Effects 0.000 description 2
239000000284 extract Substances 0.000 description 2
230000014509 gene expression Effects 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
238000003018 immunoassay Methods 0.000 description 2
238000011534 incubation Methods 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
229910001629 magnesium chloride Inorganic materials 0.000 description 2
159000000003 magnesium salts Chemical class 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
125000000896 monocarboxylic acid group Chemical group 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
230000000269 nucleophilic effect Effects 0.000 description 2
238000010534 nucleophilic substitution reaction Methods 0.000 description 2
235000020824 obesity Nutrition 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
159000000001 potassium salts Chemical class 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
150000003140 primary amides Chemical class 0.000 description 2
230000035755 proliferation Effects 0.000 description 2
FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
125000000719 pyrrolidinyl group Chemical group 0.000 description 2
150000003242 quaternary ammonium salts Chemical class 0.000 description 2
238000010791 quenching Methods 0.000 description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
239000000700 radioactive tracer Substances 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000007363 ring formation reaction Methods 0.000 description 2
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 2
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
235000019345 sodium thiosulphate Nutrition 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 2
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
GCSOXUVISUKQBS-UHFFFAOYSA-N tert-butyl 4-(3-aminophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=CC(N)=C1 GCSOXUVISUKQBS-UHFFFAOYSA-N 0.000 description 2
CNCSOOBVWRVUSB-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C=CC(N)=CC=2)=C1 CNCSOOBVWRVUSB-UHFFFAOYSA-N 0.000 description 2
RXFHRKPNLPBDGE-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C(N)C=C1 RXFHRKPNLPBDGE-UHFFFAOYSA-N 0.000 description 2
YRLQFRXDWBFGMK-UHFFFAOYSA-N tert-butyl 4-(4-aminophenyl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CC=C(N)C=C1 YRLQFRXDWBFGMK-UHFFFAOYSA-N 0.000 description 2
FXVKGMPRRHBJNX-UHFFFAOYSA-N tert-butyl n-(4-piperidin-4-ylphenyl)carbamate Chemical compound C1=CC(NC(=O)OC(C)(C)C)=CC=C1C1CCNCC1 FXVKGMPRRHBJNX-UHFFFAOYSA-N 0.000 description 2
YCQZYTQAORCNFZ-UHFFFAOYSA-N tert-butyl n-[4-[1-[2-(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl]phenyl]carbamate Chemical compound C1CN(C)CCN1CC(=O)N1CCC(C=2C=CC(NC(=O)OC(C)(C)C)=CC=2)CC1 YCQZYTQAORCNFZ-UHFFFAOYSA-N 0.000 description 2
CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 2
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
229910052722 tritium Inorganic materials 0.000 description 2
LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 description 1
OJZQOQNSUZLSMV-UHFFFAOYSA-N (3-aminophenyl)methanol Chemical compound NC1=CC=CC(CO)=C1 OJZQOQNSUZLSMV-UHFFFAOYSA-N 0.000 description 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 description 1
FPIGOBKNDYAZTP-UHFFFAOYSA-N 1,2-epoxy-3-(4-nitrophenoxy)propane Chemical compound C1=CC([N+](=O)[O-])=CC=C1OCC1OC1 FPIGOBKNDYAZTP-UHFFFAOYSA-N 0.000 description 1
125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 description 1
VHJLVAABSRFDPM-UHFFFAOYSA-N 1,4-dithiothreitol Chemical compound SCC(O)C(O)CS VHJLVAABSRFDPM-UHFFFAOYSA-N 0.000 description 1
CGXLVFZJJOXEDF-UHFFFAOYSA-N 1,8-naphthyridine-3-carboxylic acid Chemical compound N1=CC=CC2=CC(C(=O)O)=CN=C21 CGXLVFZJJOXEDF-UHFFFAOYSA-N 0.000 description 1
NTURQZFFJDCTMZ-UHFFFAOYSA-N 1-(2-bromoethyl)-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(CCBr)C=C1 NTURQZFFJDCTMZ-UHFFFAOYSA-N 0.000 description 1
AREIVWPTLISUNC-UHFFFAOYSA-N 1-(2-bromoethyl)-4-nitrobenzene;2-(4-nitrophenyl)ethanesulfonyl chloride Chemical compound [O-][N+](=O)C1=CC=C(CCBr)C=C1.[O-][N+](=O)C1=CC=C(CCS(Cl)(=O)=O)C=C1 AREIVWPTLISUNC-UHFFFAOYSA-N 0.000 description 1
BOYVZXJHUROLHZ-UHFFFAOYSA-N 1-(4-aminophenoxy)-3-(dimethylamino)propan-2-ol Chemical compound CN(C)CC(O)COC1=CC=C(N)C=C1 BOYVZXJHUROLHZ-UHFFFAOYSA-N 0.000 description 1
OPCMVVKRCLOEDQ-UHFFFAOYSA-N 1-(4-chlorophenyl)-2-(methylamino)pentan-1-one Chemical compound ClC1=CC=C(C=C1)C(C(CCC)NC)=O OPCMVVKRCLOEDQ-UHFFFAOYSA-N 0.000 description 1
SZUMSSKNCAFFQI-UHFFFAOYSA-N 1-[4-(3-aminophenyl)piperidin-1-yl]-2-(4-methylpiperazin-1-yl)ethanone Chemical compound C1CN(C)CCN1CC(=O)N1CCC(C=2C=C(N)C=CC=2)CC1 SZUMSSKNCAFFQI-UHFFFAOYSA-N 0.000 description 1
LEWASJFTWUNRCE-UHFFFAOYSA-N 1-[4-(3-aminophenyl)piperidin-1-yl]-2-(dimethylamino)ethanone Chemical compound C1CN(C(=O)CN(C)C)CCC1C1=CC=CC(N)=C1 LEWASJFTWUNRCE-UHFFFAOYSA-N 0.000 description 1
WYAQOCMPDMVCSC-UHFFFAOYSA-N 1-[4-(4-aminophenyl)piperidin-1-yl]-2-(4-methylpiperazin-1-yl)ethanone Chemical compound C1CN(C)CCN1CC(=O)N1CCC(C=2C=CC(N)=CC=2)CC1 WYAQOCMPDMVCSC-UHFFFAOYSA-N 0.000 description 1
KJVRUNVRLJMFGT-UHFFFAOYSA-N 1-[4-(4-aminophenyl)piperidin-1-yl]-2-(4-methylpiperazin-1-yl)ethanone 2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.OC(=O)C(F)(F)F.C1CN(C)CCN1CC(=O)N1CCC(C=2C=CC(N)=CC=2)CC1 KJVRUNVRLJMFGT-UHFFFAOYSA-N 0.000 description 1
IGCOVGNTLNDGRL-UHFFFAOYSA-N 1-[4-(4-aminophenyl)piperidin-1-yl]-2-(dimethylamino)ethanone tert-butyl N-[4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]carbamate Chemical compound C(C)(C)(C)OC(NC1=CC=C(C=C1)C1CCN(CC1)C(CN(C)C)=O)=O.NC1=CC=C(C=C1)C1CCN(CC1)C(CN(C)C)=O IGCOVGNTLNDGRL-UHFFFAOYSA-N 0.000 description 1
IIRKKCDXJIXWHI-UHFFFAOYSA-N 1-methyl-4-(3-nitrophenyl)piperazine Chemical compound C1CN(C)CCN1C1=CC=CC([N+]([O-])=O)=C1 IIRKKCDXJIXWHI-UHFFFAOYSA-N 0.000 description 1
QXWROCIDLCOGKL-UHFFFAOYSA-N 1-methyl-4-[(3-nitrophenyl)methyl]piperazine Chemical compound C1CN(C)CCN1CC1=CC=CC([N+]([O-])=O)=C1 QXWROCIDLCOGKL-UHFFFAOYSA-N 0.000 description 1
LEWZOBYWGWKNCK-UHFFFAOYSA-N 2,3-dihydro-1h-inden-5-amine Chemical compound NC1=CC=C2CCCC2=C1 LEWZOBYWGWKNCK-UHFFFAOYSA-N 0.000 description 1
BCWJOSZAVSHQAP-UHFFFAOYSA-N 2-(4-aminophenyl)-N-propan-2-ylethanesulfonamide 2-(4-nitrophenyl)ethanesulfonyl chloride Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)CCS(=O)(=O)Cl.C(C)(C)NS(=O)(=O)CCC1=CC=C(C=C1)N BCWJOSZAVSHQAP-UHFFFAOYSA-N 0.000 description 1
VTYRPALGSNDUQQ-UHFFFAOYSA-N 2-(dimethylamino)acetyl chloride Chemical compound CN(C)CC(Cl)=O VTYRPALGSNDUQQ-UHFFFAOYSA-N 0.000 description 1
SKYDYYQUTLAYMB-UHFFFAOYSA-N 2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxo-8-phenylpyrido[2,3-d]pyrimidine-6-carbonitrile Chemical compound C1CN(C)CCN1C(C=C1)=CC=C1NC1=NC=C2C(=O)C(C#N)=CN(C=3C=CC=CC=3)C2=N1 SKYDYYQUTLAYMB-UHFFFAOYSA-N 0.000 description 1
CUNQCKLRNYHINB-UHFFFAOYSA-N 2-amino-5-(4-methylpiperazin-1-yl)phenol Chemical compound C1CN(C)CCN1C1=CC=C(N)C(O)=C1 CUNQCKLRNYHINB-UHFFFAOYSA-N 0.000 description 1
WFRLFZAMCVAQLN-UHFFFAOYSA-N 2-fluoro-5-nitrophenol Chemical compound OC1=CC([N+]([O-])=O)=CC=C1F WFRLFZAMCVAQLN-UHFFFAOYSA-N 0.000 description 1
SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 description 1
BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 description 1
JZIBVTUXIVIFGC-UHFFFAOYSA-N 2H-pyrrole Chemical compound C1C=CC=N1 JZIBVTUXIVIFGC-UHFFFAOYSA-N 0.000 description 1
UBLZWKCJZSDBGQ-UHFFFAOYSA-N 3,5-dimethyl-1-(4-nitrophenyl)piperazine Chemical compound C1C(C)NC(C)CN1C1=CC=C([N+]([O-])=O)C=C1 UBLZWKCJZSDBGQ-UHFFFAOYSA-N 0.000 description 1
RJKFRTYBLBYVAF-UHFFFAOYSA-N 3-(3,5-dimethylpiperazin-1-yl)aniline Chemical compound C1C(C)NC(C)CN1C1=CC=CC(N)=C1 RJKFRTYBLBYVAF-UHFFFAOYSA-N 0.000 description 1
IHHKTIKNEDOMIK-UHFFFAOYSA-N 3-(morpholin-4-ylmethyl)aniline Chemical compound NC1=CC=CC(CN2CCOCC2)=C1 IHHKTIKNEDOMIK-UHFFFAOYSA-N 0.000 description 1
ZGPHZHCPWKOKDX-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]aniline Chemical compound C1CN(C)CCN1CC1=CC=CC(N)=C1 ZGPHZHCPWKOKDX-UHFFFAOYSA-N 0.000 description 1
LZPLRAXAVPPVSX-UHFFFAOYSA-N 3-amino-n,n-dimethylbenzamide Chemical compound CN(C)C(=O)C1=CC=CC(N)=C1 LZPLRAXAVPPVSX-UHFFFAOYSA-N 0.000 description 1
FENJKTQEFUPECW-UHFFFAOYSA-N 3-anilinopropanenitrile Chemical compound N#CCCNC1=CC=CC=C1 FENJKTQEFUPECW-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
BZJPIQKDEGXVFG-UHFFFAOYSA-N 3-n,3-n-dimethylbenzene-1,3-diamine;hydron;dichloride Chemical compound Cl.Cl.CN(C)C1=CC=CC(N)=C1 BZJPIQKDEGXVFG-UHFFFAOYSA-N 0.000 description 1
LLPIMIMXCXEFER-UHFFFAOYSA-N 4-(2-morpholin-4-ylethyl)aniline Chemical compound C1=CC(N)=CC=C1CCN1CCOCC1 LLPIMIMXCXEFER-UHFFFAOYSA-N 0.000 description 1
ZANPJXNYBVVNSD-UHFFFAOYSA-N 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline Chemical compound O1C(C)(C)C(C)(C)OB1C1=CC=C(N)C=C1 ZANPJXNYBVVNSD-UHFFFAOYSA-N 0.000 description 1
WNYFVEFUHMDIRQ-UHFFFAOYSA-N 4-(morpholin-4-ylmethyl)aniline Chemical compound C1=CC(N)=CC=C1CN1CCOCC1 WNYFVEFUHMDIRQ-UHFFFAOYSA-N 0.000 description 1
NIXCVBFXLJWUTC-UHFFFAOYSA-N 4-[(4-methylpiperazin-1-yl)methyl]aniline Chemical compound C1CN(C)CCN1CC1=CC=C(N)C=C1 NIXCVBFXLJWUTC-UHFFFAOYSA-N 0.000 description 1
NNCCQALFJIMRKB-UHFFFAOYSA-N 4-[(dimethylamino)methyl]aniline Chemical compound CN(C)CC1=CC=C(N)C=C1 NNCCQALFJIMRKB-UHFFFAOYSA-N 0.000 description 1
BKUWHZDNFSRARB-UHFFFAOYSA-N 4-[2-(4-methylpiperazin-1-yl)ethyl]aniline Chemical compound C1CN(C)CCN1CCC1=CC=C(N)C=C1 BKUWHZDNFSRARB-UHFFFAOYSA-N 0.000 description 1
GFFZFWAUXAFCSY-UHFFFAOYSA-N 4-[2-(4-nitrophenyl)ethyl]morpholine Chemical compound C1=CC([N+](=O)[O-])=CC=C1CCN1CCOCC1 GFFZFWAUXAFCSY-UHFFFAOYSA-N 0.000 description 1
KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 description 1
XLLVCULLOGKYOO-UHFFFAOYSA-N 4-methoxy-n-[4-[(4-methoxyphenyl)sulfonylamino]naphthalen-1-yl]benzenesulfonamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)NC(C1=CC=CC=C11)=CC=C1NS(=O)(=O)C1=CC=C(OC)C=C1 XLLVCULLOGKYOO-UHFFFAOYSA-N 0.000 description 1
PHNDZBFLOPIMSM-UHFFFAOYSA-N 4-morpholin-4-ylaniline Chemical compound C1=CC(N)=CC=C1N1CCOCC1 PHNDZBFLOPIMSM-UHFFFAOYSA-N 0.000 description 1
BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 1
CSFIQHZIFKIQNO-UHFFFAOYSA-N 4-pyrazol-1-ylaniline Chemical compound C1=CC(N)=CC=C1N1N=CC=C1 CSFIQHZIFKIQNO-UHFFFAOYSA-N 0.000 description 1
125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
LDPAPROZMMWLHL-UHFFFAOYSA-N 5,8-dihydropyrido[2,3-d]pyrimidine Chemical class C1=NC=C2CC=CNC2=N1 LDPAPROZMMWLHL-UHFFFAOYSA-N 0.000 description 1
PRSNOUWBYUJTEK-UHFFFAOYSA-N 5,8-dihydropyrido[2,3-d]pyrimidine-6-carbonitrile Chemical compound N1=CN=CC2=C1NC=C(C2)C#N PRSNOUWBYUJTEK-UHFFFAOYSA-N 0.000 description 1
UIMITVXKLSQWEI-UHFFFAOYSA-N 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[2-(4-methylpiperazin-1-yl)ethyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1CN(C)CCN1CCC(C=C1)=CC=C1NC1=NC=C2C(=O)C(C(O)=O)=CN(C=3C=C4CCCC4=CC=3)C2=N1 UIMITVXKLSQWEI-UHFFFAOYSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
SZZLQTFOECJTOL-UHFFFAOYSA-N BrCCC1=CC=C(C=C1)[N+](=O)[O-].N1(CCOCC1)CCC1=CC=C(C=C1)N Chemical compound BrCCC1=CC=C(C=C1)[N+](=O)[O-].N1(CCOCC1)CCC1=CC=C(C=C1)N SZZLQTFOECJTOL-UHFFFAOYSA-N 0.000 description 1
YETKGPWCKZRJLT-UHFFFAOYSA-L C([O-])([O-])=O.[K+].[N+](=O)([O-])C1=CC=C(OCC2OC2)C=C1.[K+] Chemical compound C([O-])([O-])=O.[K+].[N+](=O)([O-])C1=CC=C(OCC2OC2)C=C1.[K+] YETKGPWCKZRJLT-UHFFFAOYSA-L 0.000 description 1
RZGOSGVWEYYHPC-UHFFFAOYSA-N C1(CCCC1)N.C(C)OC(CCNC1CCCC1)=O Chemical compound C1(CCCC1)N.C(C)OC(CCNC1CCCC1)=O RZGOSGVWEYYHPC-UHFFFAOYSA-N 0.000 description 1
FCWRPXYQFJGDCR-UHFFFAOYSA-N C1(CCCCC1)N.C(C)OC(CCNC1CCCCC1)=O Chemical compound C1(CCCCC1)N.C(C)OC(CCNC1CCCCC1)=O FCWRPXYQFJGDCR-UHFFFAOYSA-N 0.000 description 1
SJRIMDKWEDPNCY-UHFFFAOYSA-N C12C(CC(CC1)C2)N.C(C)OC(CCNC2C1CCC(C2)C1)=O Chemical compound C12C(CC(CC1)C2)N.C(C)OC(CCNC2C1CCC(C2)C1)=O SJRIMDKWEDPNCY-UHFFFAOYSA-N 0.000 description 1
SCQSSVSMDHGKRG-UHFFFAOYSA-N CN(C(=O)C=1C=C(C=CC1)NC=1N=CC2=C(N1)N(C=C(C2=O)C(=O)O)C=2C=C1CCCC1=CC2)C Chemical compound CN(C(=O)C=1C=C(C=CC1)NC=1N=CC2=C(N1)N(C=C(C2=O)C(=O)O)C=2C=C1CCCC1=CC2)C SCQSSVSMDHGKRG-UHFFFAOYSA-N 0.000 description 1
XDJHBVWAYUADAK-UHFFFAOYSA-N CN(C)CC(=O)Cl.NC1=CC=C(C=C1)C1CN(CCC1)C(CN(C)C)=O Chemical compound CN(C)CC(=O)Cl.NC1=CC=C(C=C1)C1CN(CCC1)C(CN(C)C)=O XDJHBVWAYUADAK-UHFFFAOYSA-N 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
206010009944 Colon cancer Diseases 0.000 description 1
229920000858 Cyclodextrin Polymers 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
208000009386 Experimental Arthritis Diseases 0.000 description 1
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
206010023203 Joint destruction Diseases 0.000 description 1
229930194542 Keto Natural products 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
206010058467 Lung neoplasm malignant Diseases 0.000 description 1
108010006035 Metalloproteases Proteins 0.000 description 1
102000005741 Metalloproteases Human genes 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
206010033128 Ovarian cancer Diseases 0.000 description 1
206010061535 Ovarian neoplasm Diseases 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
241001111421 Pannus Species 0.000 description 1
102000001938 Plasminogen Activators Human genes 0.000 description 1
108010001014 Plasminogen Activators Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
241000219061 Rheum Species 0.000 description 1
208000005718 Stomach Neoplasms Diseases 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
WFWLQNSHRPWKFK-UHFFFAOYSA-N Tegafur Chemical group O=C1NC(=O)C(F)=CN1C1OCCC1 WFWLQNSHRPWKFK-UHFFFAOYSA-N 0.000 description 1
108010009583 Transforming Growth Factors Proteins 0.000 description 1
102000009618 Transforming Growth Factors Human genes 0.000 description 1
208000002495 Uterine Neoplasms Diseases 0.000 description 1
108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 1
102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 1
108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 1
OGZMWAPSXBIOMS-UHFFFAOYSA-M [Br-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)OC(CCNC=1C=C2CCCC2=CC1)=O Chemical compound [Br-].C(CCC)[N+](CCCC)(CCCC)CCCC.C(C)OC(CCNC=1C=C2CCCC2=CC1)=O OGZMWAPSXBIOMS-UHFFFAOYSA-M 0.000 description 1
JLDBVFFKQALHDN-UHFFFAOYSA-N [Br].C(C)OC(=O)C=1C(C2=C(N=C(N=C2)SC)N(C1)C1CCCCC1)=O Chemical compound [Br].C(C)OC(=O)C=1C(C2=C(N=C(N=C2)SC)N(C1)C1CCCCC1)=O JLDBVFFKQALHDN-UHFFFAOYSA-N 0.000 description 1
RXZSBKIOEXNWPX-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C(C=C1)CCS(=O)(=O)Cl.N1(CCOCC1)S(=O)(=O)CCC1=CC=C(C=C1)N Chemical compound [N+](=O)([O-])C1=CC=C(C=C1)CCS(=O)(=O)Cl.N1(CCOCC1)S(=O)(=O)CCC1=CC=C(C=C1)N RXZSBKIOEXNWPX-UHFFFAOYSA-N 0.000 description 1
JKWTZLLGEGBRCV-UHFFFAOYSA-N [Na].C(C)OC(=O)C1C(C2=C(N=C(N=C2)SC)N(C1)C1CCCCC1)=O Chemical compound [Na].C(C)OC(=O)C1C(C2=C(N=C(N=C2)SC)N(C1)C1CCCCC1)=O JKWTZLLGEGBRCV-UHFFFAOYSA-N 0.000 description 1
JLFVIEQMRKMAIT-UHFFFAOYSA-N ac1l9mnz Chemical group O.O.O JLFVIEQMRKMAIT-UHFFFAOYSA-N 0.000 description 1
125000004062 acenaphthenyl group Chemical group C1(CC2=CC=CC3=CC=CC1=C23)* 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
230000006978 adaptation Effects 0.000 description 1
WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
210000000577 adipose tissue Anatomy 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
239000012670 alkaline solution Substances 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
150000003973 alkyl amines Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000010640 amide synthesis reaction Methods 0.000 description 1
150000008362 aminopropionitriles Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
229940121375 antifungal agent Drugs 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
150000005840 aryl radicals Chemical class 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 description 1
125000003725 azepanyl group Chemical group 0.000 description 1
125000002393 azetidinyl group Chemical group 0.000 description 1
125000003828 azulenyl group Chemical group 0.000 description 1
230000008901 benefit Effects 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000004305 biphenyl Substances 0.000 description 1
235000010290 biphenyl Nutrition 0.000 description 1
ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical class OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
125000005620 boronic acid group Chemical class 0.000 description 1
238000006795 borylation reaction Methods 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
235000013877 carbamide Nutrition 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
150000001733 carboxylic acid esters Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
125000002091 cationic group Chemical group 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
230000036755 cellular response Effects 0.000 description 1
KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
208000037976 chronic inflammation Diseases 0.000 description 1
230000006020 chronic inflammation Effects 0.000 description 1
125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
229940090805 clavulanate Drugs 0.000 description 1
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
238000000576 coating method Methods 0.000 description 1
208000029742 colonic neoplasm Diseases 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
230000001086 cytosolic effect Effects 0.000 description 1
229940127089 cytotoxic agent Drugs 0.000 description 1
125000005508 decahydronaphthalenyl group Chemical group 0.000 description 1
238000006114 decarboxylation reaction Methods 0.000 description 1
238000006704 dehydrohalogenation reaction Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
230000001066 destructive effect Effects 0.000 description 1
229910052805 deuterium Inorganic materials 0.000 description 1
150000005690 diesters Chemical class 0.000 description 1
125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
238000006471 dimerization reaction Methods 0.000 description 1
SPCNPOWOBZQWJK-UHFFFAOYSA-N dimethoxy-(2-propan-2-ylsulfanylethylsulfanyl)-sulfanylidene-$l^{5}-phosphane Chemical compound COP(=S)(OC)SCCSC(C)C SPCNPOWOBZQWJK-UHFFFAOYSA-N 0.000 description 1
239000001177 diphosphate Substances 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
HPLBNSXFSQMHKV-UHFFFAOYSA-L dipotassium 4-(4-methylpiperazin-1-yl)aniline carbonate Chemical compound C([O-])([O-])=O.[K+].CN1CCN(CC1)C1=CC=C(C=C1)N.[K+] HPLBNSXFSQMHKV-UHFFFAOYSA-L 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
239000002612 dispersion medium Substances 0.000 description 1
MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 1
229940043264 dodecyl sulfate Drugs 0.000 description 1
229940009662 edetate Drugs 0.000 description 1
230000002526 effect on cardiovascular system Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
GKIPXFAANLTWBM-UHFFFAOYSA-N epibromohydrin Chemical compound BrCC1CO1 GKIPXFAANLTWBM-UHFFFAOYSA-N 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
NPPUUYOFPPPOCX-UHFFFAOYSA-N ethyl 3-(3-bicyclo[2.2.1]heptanylamino)propanoate Chemical compound C1CC2C(NCCC(=O)OCC)CC1C2 NPPUUYOFPPPOCX-UHFFFAOYSA-N 0.000 description 1
KPOUXRWDVDBJSQ-UHFFFAOYSA-N ethyl 3-(benzylamino)propanoate ethyl 4-[benzyl-(3-ethoxy-3-oxopropyl)amino]-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound C(C)OC(CCNCC1=CC=CC=C1)=O.C(C)OC(=O)C=1C(=NC(=NC1)SC)N(CCC(=O)OCC)CC1=CC=CC=C1 KPOUXRWDVDBJSQ-UHFFFAOYSA-N 0.000 description 1
MKGGIUMRJNGHRE-UHFFFAOYSA-N ethyl 3-(cyclohexylamino)propanoate;ethyl 4-[cyclohexyl-(3-ethoxy-3-oxopropyl)amino]-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound CCOC(=O)CCNC1CCCCC1.N=1C(SC)=NC=C(C(=O)OCC)C=1N(CCC(=O)OCC)C1CCCCC1 MKGGIUMRJNGHRE-UHFFFAOYSA-N 0.000 description 1
PGGWSUSDGRDUFX-UHFFFAOYSA-N ethyl 3-(cyclopentylamino)propanoate Chemical compound CCOC(=O)CCNC1CCCC1 PGGWSUSDGRDUFX-UHFFFAOYSA-N 0.000 description 1
LCZURJBQGZDFMZ-UHFFFAOYSA-N ethyl 4-[2,3-dihydro-1h-inden-5-yl-(3-ethoxy-3-oxopropyl)amino]-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound C=1C=C2CCCC2=CC=1N(CCC(=O)OCC)C1=NC(SC)=NC=C1C(=O)OCC LCZURJBQGZDFMZ-UHFFFAOYSA-N 0.000 description 1
FVJBFRAJVMLUIW-UHFFFAOYSA-N ethyl 4-[3-bicyclo[2.2.1]heptanyl-(3-ethoxy-3-oxopropyl)amino]-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound C1C(C2)CCC2C1N(CCC(=O)OCC)C1=NC(SC)=NC=C1C(=O)OCC FVJBFRAJVMLUIW-UHFFFAOYSA-N 0.000 description 1
LUYPTNXKKZDUHQ-UHFFFAOYSA-N ethyl 4-[cyclohexyl-(3-ethoxy-3-oxopropyl)amino]-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound N=1C(SC)=NC=C(C(=O)OCC)C=1N(CCC(=O)OCC)C1CCCCC1 LUYPTNXKKZDUHQ-UHFFFAOYSA-N 0.000 description 1
BBUKIVAIRPTLEV-UHFFFAOYSA-N ethyl 4-[cyclopentyl-(3-ethoxy-3-oxopropyl)amino]-2-methylsulfanylpyrimidine-5-carboxylate Chemical compound N=1C(SC)=NC=C(C(=O)OCC)C=1N(CCC(=O)OCC)C1CCCC1 BBUKIVAIRPTLEV-UHFFFAOYSA-N 0.000 description 1
QDHHLXABEXNRJX-UHFFFAOYSA-N ethyl 4-hydroxy-6-oxo-1h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CNC(O)=CC1=O QDHHLXABEXNRJX-UHFFFAOYSA-N 0.000 description 1
OOOULHOQJDXVFO-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[3-[(dimethylamino)methyl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC1=CC=CC(CN(C)C)=C1 OOOULHOQJDXVFO-UHFFFAOYSA-N 0.000 description 1
YSENUZVVFFFQDH-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(2-morpholin-4-ylsulfonylethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CCS(=O)(=O)N1CCOCC1 YSENUZVVFFFQDH-UHFFFAOYSA-N 0.000 description 1
KMOBNLFAGFFBRG-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-(morpholin-4-ylmethyl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1CN1CCOCC1 KMOBNLFAGFFBRG-UHFFFAOYSA-N 0.000 description 1
MGCPDXGSUQWATN-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-[4-[1-[2-(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl]anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C(CC1)CCN1C(=O)CN1CCN(C)CC1 MGCPDXGSUQWATN-UHFFFAOYSA-N 0.000 description 1
CEKAKZVNGSUFFY-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-2-methylsulfanyl-5-oxo-6,7-dihydropyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(SC)=NC=C2C(=O)C(C(=O)OCC)CN1C1=CC=C(CCC2)C2=C1 CEKAKZVNGSUFFY-UHFFFAOYSA-N 0.000 description 1
PPGHTKCZIUTGNE-UHFFFAOYSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-(4-piperidin-4-ylanilino)pyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C1CCNCC1 PPGHTKCZIUTGNE-UHFFFAOYSA-N 0.000 description 1
YTSWKFHTHUFBJF-NRFANRHFSA-N ethyl 8-(2,3-dihydro-1h-inden-5-yl)-5-oxo-2-[4-[[(4s)-2-oxo-1,3-oxazolidin-4-yl]methyl]anilino]pyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound N=1C=C2C(=O)C(C(=O)OCC)=CN(C=3C=C4CCCC4=CC=3)C2=NC=1NC(C=C1)=CC=C1C[C@H]1COC(=O)N1 YTSWKFHTHUFBJF-NRFANRHFSA-N 0.000 description 1
SZFXFEIAMLISBW-UHFFFAOYSA-N ethyl 8-(3-bicyclo[2.2.1]heptanyl)-2-methylsulfanyl-5-oxo-6,7-dihydropyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(SC)=NC=C2C(=O)C(C(=O)OCC)CN1C1C(C2)CCC2C1 SZFXFEIAMLISBW-UHFFFAOYSA-N 0.000 description 1
UIPPBRAXLVAUKD-UHFFFAOYSA-N ethyl 8-benzyl-2-[4-(4-methylpiperazin-1-yl)anilino]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(NC=3C=CC(=CC=3)N3CCN(C)CC3)=NC=C2C(=O)C(C(=O)OCC)=CN1CC1=CC=CC=C1 UIPPBRAXLVAUKD-UHFFFAOYSA-N 0.000 description 1
HNPLLRSCVABZOB-UHFFFAOYSA-N ethyl 8-benzyl-2-methylsulfanyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(SC)=NC=C2C(=O)C(C(=O)OCC)=CN1CC1=CC=CC=C1 HNPLLRSCVABZOB-UHFFFAOYSA-N 0.000 description 1
LQAOPVDMQMIBNP-UHFFFAOYSA-N ethyl 8-benzyl-2-methylsulfonyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(S(C)(=O)=O)=NC=C2C(=O)C(C(=O)OCC)=CN1CC1=CC=CC=C1 LQAOPVDMQMIBNP-UHFFFAOYSA-N 0.000 description 1
BNFFYWGBKUMGHS-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-methylsulfanyl-5-oxo-6,7-dihydropyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(SC)=NC=C2C(=O)C(C(=O)OCC)CN1C1CCCCC1 BNFFYWGBKUMGHS-UHFFFAOYSA-N 0.000 description 1
LDPQTMPWDSXTDF-UHFFFAOYSA-N ethyl 8-cyclohexyl-2-methylsulfanyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(SC)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCCC1 LDPQTMPWDSXTDF-UHFFFAOYSA-N 0.000 description 1
JRKUDJGMPOLVGK-UHFFFAOYSA-N ethyl 8-cyclopentyl-2-methylsulfanyl-5-oxo-6,7-dihydropyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(SC)=NC=C2C(=O)C(C(=O)OCC)CN1C1CCCC1 JRKUDJGMPOLVGK-UHFFFAOYSA-N 0.000 description 1
QBNBJHUVMLBUGO-UHFFFAOYSA-N ethyl 8-cyclopentyl-2-methylsulfanyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(SC)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCC1 QBNBJHUVMLBUGO-UHFFFAOYSA-N 0.000 description 1
XXRHPFJHQATHAE-UHFFFAOYSA-N ethyl 8-cyclopentyl-2-methylsulfonyl-5-oxopyrido[2,3-d]pyrimidine-6-carboxylate Chemical compound C12=NC(S(C)(=O)=O)=NC=C2C(=O)C(C(=O)OCC)=CN1C1CCCC1 XXRHPFJHQATHAE-UHFFFAOYSA-N 0.000 description 1
239000000945 filler Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
238000009472 formulation Methods 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
206010017758 gastric cancer Diseases 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
229930195712 glutamate Natural products 0.000 description 1
229940049906 glutamate Drugs 0.000 description 1
230000003394 haemopoietic effect Effects 0.000 description 1
201000009277 hairy cell leukemia Diseases 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
230000026030 halogenation Effects 0.000 description 1
238000005658 halogenation reaction Methods 0.000 description 1
230000036541 health Effects 0.000 description 1
IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 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
XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
125000002632 imidazolidinyl group Chemical group 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
238000011835 investigation Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 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
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
239000007951 isotonicity adjuster Substances 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
201000005296 lung carcinoma Diseases 0.000 description 1
229940049920 malate Drugs 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
239000003550 marker Substances 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
238000005259 measurement Methods 0.000 description 1
239000002207 metabolite Chemical group 0.000 description 1
MJMZBXYBWMBFNY-UHFFFAOYSA-N methyl 4-(4-nitrophenoxy)butanoate Chemical compound COC(=O)CCCOC1=CC=C([N+]([O-])=O)C=C1 MJMZBXYBWMBFNY-UHFFFAOYSA-N 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
210000001616 monocyte Anatomy 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
201000008383 nephritis Diseases 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
229910000069 nitrogen hydride Inorganic materials 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
150000002895 organic esters Chemical class 0.000 description 1
239000013110 organic ligand Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
125000004430 oxygen atom Chemical group O* 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
230000026731 phosphorylation Effects 0.000 description 1
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
229950010765 pivalate Drugs 0.000 description 1
IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
229940127126 plasminogen activator Drugs 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003072 pyrazolidinyl 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
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
102000027426 receptor tyrosine kinases Human genes 0.000 description 1
108091008598 receptor tyrosine kinases Proteins 0.000 description 1
238000010992 reflux Methods 0.000 description 1
125000006413 ring segment Chemical group 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-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
230000011664 signaling Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
150000003384 small molecules Chemical class 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
239000007858 starting material Substances 0.000 description 1
201000011549 stomach cancer Diseases 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
229940124530 sulfonamide Drugs 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
MGYCIJUTYLUYJM-UHFFFAOYSA-N tert-butyl 4-(4-nitrophenyl)piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1C1=CC=C([N+]([O-])=O)C=C1 MGYCIJUTYLUYJM-UHFFFAOYSA-N 0.000 description 1
WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
ZEUKXBJMTZOQLK-UHFFFAOYSA-N tert-butyl n-[3-[1-[2-(4-methylpiperazin-1-yl)acetyl]piperidin-4-yl]phenyl]carbamate Chemical compound C1CN(C)CCN1CC(=O)N1CCC(C=2C=C(NC(=O)OC(C)(C)C)C=CC=2)CC1 ZEUKXBJMTZOQLK-UHFFFAOYSA-N 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
DUYAAUVXQSMXQP-UHFFFAOYSA-M thioacetate Chemical compound CC([S-])=O DUYAAUVXQSMXQP-UHFFFAOYSA-M 0.000 description 1
125000005505 thiomorpholino group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
230000007838 tissue remodeling Effects 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
150000003672 ureas Chemical class 0.000 description 1
206010046766 uterine cancer Diseases 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
239000001993 wax Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1