CA2260061A1 - Bicyclic heteroaromatic compounds as protein tyrosine kinase inhibitors - Google Patents

Info

Publication number

CA2260061A1

CA2260061A1 CA002260061A CA2260061A CA2260061A1 CA 2260061 A1 CA2260061 A1 CA 2260061A1 CA 002260061 A CA002260061 A CA 002260061A CA 2260061 A CA2260061 A CA 2260061A CA 2260061 A1 CA2260061 A1 CA 2260061A1

Authority

CA

Canada

Prior art keywords

group

compound

alkyl

pyrido

benzyl

Prior art date

1996-07-13

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• -1 Bicyclic heteroaromatic compounds Chemical class 0.000 title claims abstract description 259
• 239000005483 tyrosine kinase inhibitor Substances 0.000 title abstract 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 228
• 238000000034 method Methods 0.000 claims abstract description 80
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 34
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 30
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 29
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 29
• 238000011282 treatment Methods 0.000 claims abstract description 27
• 238000002360 preparation method Methods 0.000 claims abstract description 24
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 21
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
• 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims abstract description 18
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 17
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 9
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 8
• 201000004681 Psoriasis Diseases 0.000 claims abstract description 8
• 125000004429 atom Chemical group 0.000 claims abstract description 8
• 201000011510 cancer Diseases 0.000 claims abstract description 8
• 239000003814 drug Substances 0.000 claims abstract description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 8
• 125000000217 alkyl group Chemical group 0.000 claims description 114
• 229910052739 hydrogen Inorganic materials 0.000 claims description 90
• 239000001257 hydrogen Substances 0.000 claims description 77
• 125000003282 alkyl amino group Chemical group 0.000 claims description 55
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 44
• 125000003545 alkoxy group Chemical group 0.000 claims description 43
• 238000006243 chemical reaction Methods 0.000 claims description 43
• 150000003839 salts Chemical class 0.000 claims description 39
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 36
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 34
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
• 229910052757 nitrogen Inorganic materials 0.000 claims description 29
• 239000003153 chemical reaction reagent Substances 0.000 claims description 28
• 239000012453 solvate Substances 0.000 claims description 28
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
• 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 26
• 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 26
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 24
• 230000000694 effects Effects 0.000 claims description 24
• 125000005843 halogen group Chemical group 0.000 claims description 23
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 20
• 230000008569 process Effects 0.000 claims description 19
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
• 125000001424 substituent group Chemical group 0.000 claims description 17
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 15
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14
• 229910052736 halogen Inorganic materials 0.000 claims description 14
• 150000002367 halogens Chemical class 0.000 claims description 14
• 125000001041 indolyl group Chemical group 0.000 claims description 14
• 208000035475 disorder Diseases 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 12
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
• 125000003118 aryl group Chemical group 0.000 claims description 12
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• 125000004175 fluorobenzyl group Chemical group 0.000 claims description 12
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 11
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 11
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 11
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 10
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 10
• 125000005879 dioxolanyl group Chemical group 0.000 claims description 10
• WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 10
• QCEPAUUUYZXMGD-UHFFFAOYSA-N 4-chloro-n,n-dimethylpyrido[3,4-d]pyrimidin-6-amine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1Cl QCEPAUUUYZXMGD-UHFFFAOYSA-N 0.000 claims description 9
• 125000004414 alkyl thio group Chemical group 0.000 claims description 9
• 150000003852 triazoles Chemical class 0.000 claims description 9
• 230000001594 aberrant effect Effects 0.000 claims description 8
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 8
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 8
• 230000001404 mediated effect Effects 0.000 claims description 8
• QNDFCSITSCMNGP-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 QNDFCSITSCMNGP-UHFFFAOYSA-N 0.000 claims description 8
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
• CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 7
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
• 150000004702 methyl esters Chemical class 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 150000003536 tetrazoles Chemical class 0.000 claims description 7
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 6
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 6
• 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 6
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 5
• 241001465754 Metazoa Species 0.000 claims description 5
• PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 5
• CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 5
• 229930192474 thiophene Natural products 0.000 claims description 5
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
• BMIOWXJYLRLVHA-UHFFFAOYSA-N 4-n-(1-benzylindazol-5-yl)-6-n-methylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(NC)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 BMIOWXJYLRLVHA-UHFFFAOYSA-N 0.000 claims description 4
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 4
• DYYZXRCFCVDSKD-UHFFFAOYSA-N N6,N6-dimethyl-N4-[1-(phenylmethyl)-5-indazolyl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 DYYZXRCFCVDSKD-UHFFFAOYSA-N 0.000 claims description 4
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
• 150000001408 amides Chemical class 0.000 claims description 4
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
• 125000004989 dicarbonyl group Chemical group 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
• 125000004193 piperazinyl group Chemical group 0.000 claims description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• BWESROVQGZSBRX-UHFFFAOYSA-N pyrido[3,2-d]pyrimidine Chemical group C1=NC=NC2=CC=CN=C21 BWESROVQGZSBRX-UHFFFAOYSA-N 0.000 claims description 4
• 229920006395 saturated elastomer Polymers 0.000 claims description 4
• BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 claims description 4
• 125000001544 thienyl group Chemical group 0.000 claims description 4
• 229910052721 tungsten Inorganic materials 0.000 claims description 4
• JFXFEXXASOCJBR-UHFFFAOYSA-N 4-n-(1-benzylindazol-5-yl)-6-n-ethyl-6-n-methylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)CC)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 JFXFEXXASOCJBR-UHFFFAOYSA-N 0.000 claims description 3
• HKNPEKHQRROZPD-UHFFFAOYSA-N 4-n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC(F)=C1 HKNPEKHQRROZPD-UHFFFAOYSA-N 0.000 claims description 3
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 3
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
• 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 3
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 3
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 3
• GIZAHSJRRRUFEE-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(1,3-dioxolan-2-yl)furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)C=3OC(=CC=3)C3OCCO3)=CC=C2N1CC1=CC=CC=C1 GIZAHSJRRRUFEE-UHFFFAOYSA-N 0.000 claims description 3
• DUNKZQKFWZSBHG-UHFFFAOYSA-N n-(1-benzylindol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1C=C2)=CC=C1N2CC1=CC=CC=C1 DUNKZQKFWZSBHG-UHFFFAOYSA-N 0.000 claims description 3
• 239000001301 oxygen Substances 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 238000002560 therapeutic procedure Methods 0.000 claims description 3
• 125000005955 1H-indazolyl group Chemical group 0.000 claims description 2
• UMFFMOFETJMRSZ-UHFFFAOYSA-N 2-[4-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]piperazin-1-yl]-1-morpholin-4-ylethanone Chemical compound C1COCCN1C(=O)CN(CC1)CCN1C(N=CC1=NC=N2)=CC1=C2NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 UMFFMOFETJMRSZ-UHFFFAOYSA-N 0.000 claims description 2
• YZZIGXZRNAEFCP-UHFFFAOYSA-N 4-n-(1-benzylindol-5-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=C2)=CC=C1N2CC1=CC=CC=C1 YZZIGXZRNAEFCP-UHFFFAOYSA-N 0.000 claims description 2
• RCDUEGIHNAMABT-UHFFFAOYSA-N 4-n-(2-benzyl-3h-benzimidazol-5-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1N2)=CC=C1N=C2CC1=CC=CC=C1 RCDUEGIHNAMABT-UHFFFAOYSA-N 0.000 claims description 2
• BIQOFKWYWPJGNB-UHFFFAOYSA-N 4-n-[1-(benzenesulfonyl)indol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=C2)=CC=C1N2S(=O)(=O)C1=CC=CC=C1 BIQOFKWYWPJGNB-UHFFFAOYSA-N 0.000 claims description 2
• HBOLGDVBJIQIQE-UHFFFAOYSA-N 4-n-[1-[(2-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1F HBOLGDVBJIQIQE-UHFFFAOYSA-N 0.000 claims description 2
• OLTKCLCQFKBLKU-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]-n-(2-methylsulfonylethyl)furan-2-carboxamide Chemical compound O1C(C(=O)NCCS(=O)(=O)C)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 OLTKCLCQFKBLKU-UHFFFAOYSA-N 0.000 claims description 2
• JCMRKIPIHJRILY-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 JCMRKIPIHJRILY-UHFFFAOYSA-N 0.000 claims description 2
• FOXGCSWJHNGAHI-UHFFFAOYSA-N 6-(dimethylamino)-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound N1=CNC(=O)C2=C1C=NC(N(C)C)=C2 FOXGCSWJHNGAHI-UHFFFAOYSA-N 0.000 claims description 2
• VKPHMHJHCQWKKV-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-[1-(pyridin-2-ylmethyl)indazol-5-yl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=N1 VKPHMHJHCQWKKV-UHFFFAOYSA-N 0.000 claims description 2
• USTNKMJFNDVPLS-UHFFFAOYSA-N 6-n,6-n-dimethyl-4-n-[1-(pyridin-3-ylmethyl)indazol-5-yl]pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=CN=C1 USTNKMJFNDVPLS-UHFFFAOYSA-N 0.000 claims description 2
• 239000004471 Glycine Substances 0.000 claims description 2
• 229910052770 Uranium Inorganic materials 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 claims description 2
• BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 2
• KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical group COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims description 2
• FRHWAVXLZREEEK-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(C)=NN=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 FRHWAVXLZREEEK-UHFFFAOYSA-N 0.000 claims description 2
• NEHINJYPPQYUQH-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-imidazol-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3C=NC=C3)=CC=C2N1CC1=CC=CC=C1 NEHINJYPPQYUQH-UHFFFAOYSA-N 0.000 claims description 2
• WVIYDZAMWSNDDO-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-pyrrolidin-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC(=NC=C4N=CN=3)N3CCCC3)=CC=C2N1CC1=CC=CC=C1 WVIYDZAMWSNDDO-UHFFFAOYSA-N 0.000 claims description 2
• COGNCPVOUZUOSK-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CC2=CC(NC=3C4=CC=NC=C4N=CN=3)=CC=C2N1CC1=CC=CC=C1 COGNCPVOUZUOSK-UHFFFAOYSA-N 0.000 claims description 2
• YCPVGYFQXXTANI-UHFFFAOYSA-N n-(2-benzyl-3h-benzimidazol-5-yl)-6-chloropyrido[3,4-d]pyrimidin-4-amine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1NC(C=C1N=2)=CC=C1NC=2CC1=CC=CC=C1 YCPVGYFQXXTANI-UHFFFAOYSA-N 0.000 claims description 2
• QLNPJNIYZWVSMB-UHFFFAOYSA-N n-[1-[(3-fluorophenyl)methyl]indazol-5-yl]-6-(5-methyl-1,3,4-oxadiazol-2-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1C(C)=NN=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=C(F)C=CC=2)N=C2)C2=C1 QLNPJNIYZWVSMB-UHFFFAOYSA-N 0.000 claims description 2
• 125000005554 pyridyloxy group Chemical group 0.000 claims description 2
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
• 229910052727 yttrium Inorganic materials 0.000 claims description 2
• 150000002431 hydrogen Chemical class 0.000 claims 7
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 2
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 1
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
• MAAXBKQABSWUKL-UHFFFAOYSA-N 2-[4-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]piperazin-1-yl]-n-propan-2-ylacetamide Chemical compound C1CN(CC(=O)NC(C)C)CCN1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 MAAXBKQABSWUKL-UHFFFAOYSA-N 0.000 claims 1
• NQRIHPCAOWTVBX-UHFFFAOYSA-N 2-[[2-(methanesulfonamido)ethylamino]-[(2-methylsulfinylethylamino)-(3-methylsulfinylpropylamino)-(3-methylsulfonylpropylamino)methyl]amino]-2-(2-methylsulfonylethylamino)acetamide Chemical compound CS(=O)CCCNC(NCCCS(C)(=O)=O)(NCCS(C)=O)N(NCCNS(C)(=O)=O)C(NCCS(C)(=O)=O)C(N)=O NQRIHPCAOWTVBX-UHFFFAOYSA-N 0.000 claims 1
• XKGUJMPYDBMSDA-UHFFFAOYSA-N 4-n-(1-benzyl-3-methylindazol-5-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C(C)=N2)=CC=C1N2CC1=CC=CC=C1 XKGUJMPYDBMSDA-UHFFFAOYSA-N 0.000 claims 1
• MQNRGKYCHYKEMO-UHFFFAOYSA-N 4-n-[1-[(4-fluorophenyl)methyl]indazol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1C=N2)=CC=C1N2CC1=CC=C(F)C=C1 MQNRGKYCHYKEMO-UHFFFAOYSA-N 0.000 claims 1
• OCCGRAZNBVMQAO-UHFFFAOYSA-N 4-n-[3-(benzenesulfonyl)-1h-indol-5-yl]-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C12)=CC=C1NC=C2S(=O)(=O)C1=CC=CC=C1 OCCGRAZNBVMQAO-UHFFFAOYSA-N 0.000 claims 1
• RLCKHNKPUUYNQD-UHFFFAOYSA-N 5-[4-[(1-benzylindazol-5-yl)amino]pyrido[3,4-d]pyrimidin-6-yl]furan-2-carbaldehyde Chemical compound O1C(C=O)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 RLCKHNKPUUYNQD-UHFFFAOYSA-N 0.000 claims 1
• 239000002552 dosage form Substances 0.000 claims 1
• UZXVIZOKQMXWKF-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(3-methylimidazol-4-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound CN1C=NC=C1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 UZXVIZOKQMXWKF-UHFFFAOYSA-N 0.000 claims 1
• WWAHWFCQESJGIU-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-(4-methylpiperazin-1-yl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(N(CC=2C=CC=CC=2)N=C2)C2=C1 WWAHWFCQESJGIU-UHFFFAOYSA-N 0.000 claims 1
• 125000004122 cyclic group Chemical group 0.000 abstract description 6
• 125000004432 carbon atom Chemical group C* 0.000 abstract description 5
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 abstract description 4
• 125000002950 monocyclic group Chemical group 0.000 abstract description 4
• 125000000714 pyrimidinyl group Chemical group 0.000 abstract description 3
• 125000003341 7 membered heterocyclic group Chemical group 0.000 abstract description 2
• 150000002390 heteroarenes Chemical class 0.000 abstract description 2
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 137
• 239000000203 mixture Substances 0.000 description 58
• 239000007787 solid Substances 0.000 description 41
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 38
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 33
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 32
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• 239000000243 solution Substances 0.000 description 27
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
• 101710100968 Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 17
• 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 17
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
• 239000000047 product Substances 0.000 description 14
• 125000005236 alkanoylamino group Chemical group 0.000 description 13
• 210000004027 cell Anatomy 0.000 description 13
• 235000019439 ethyl acetate Nutrition 0.000 description 13
• 238000010992 reflux Methods 0.000 description 13
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
• 229940093499 ethyl acetate Drugs 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• 150000001412 amines Chemical class 0.000 description 11
• 239000000377 silicon dioxide Substances 0.000 description 11
• 108060006698 EGF receptor Proteins 0.000 description 10
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
• 238000009472 formulation Methods 0.000 description 10
• 239000003112 inhibitor Substances 0.000 description 10
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
• 239000002253 acid Substances 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 8
• 238000004587 chromatography analysis Methods 0.000 description 8
• 230000005764 inhibitory process Effects 0.000 description 8
• 239000002904 solvent Substances 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• 239000004480 active ingredient Substances 0.000 description 7
• 125000002837 carbocyclic group Chemical group 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• 239000000543 intermediate Substances 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 102000027426 receptor tyrosine kinases Human genes 0.000 description 6
• 108091008598 receptor tyrosine kinases Proteins 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• UYDNPZLYDODKKA-UHFFFAOYSA-N 1-benzylindol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1 UYDNPZLYDODKKA-UHFFFAOYSA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
• 239000012298 atmosphere Substances 0.000 description 5
• 125000001309 chloro group Chemical group Cl* 0.000 description 5
• 239000006071 cream Substances 0.000 description 5
• 239000000706 filtrate Substances 0.000 description 5
• 238000004128 high performance liquid chromatography Methods 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 229910052763 palladium Inorganic materials 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 150000003246 quinazolines Chemical class 0.000 description 5
• CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
• 238000003786 synthesis reaction Methods 0.000 description 5
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 4
• BQUSMTPKYUILPD-UHFFFAOYSA-N 1-benzylindazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1 BQUSMTPKYUILPD-UHFFFAOYSA-N 0.000 description 4
• BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 4
• 206010006187 Breast cancer Diseases 0.000 description 4
• 208000026310 Breast neoplasm Diseases 0.000 description 4
• CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
• 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 4
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
• 101150093908 PDGFRB gene Proteins 0.000 description 4
• 102000001332 SRC Human genes 0.000 description 4
• 108060006706 SRC Proteins 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 229960004132 diethyl ether Drugs 0.000 description 4
• 201000010099 disease Diseases 0.000 description 4
• 230000012010 growth Effects 0.000 description 4
• 125000001072 heteroaryl group Chemical group 0.000 description 4
• 230000036210 malignancy Effects 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 125000001624 naphthyl group Chemical group 0.000 description 4
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
• 229960005141 piperazine Drugs 0.000 description 4
• 125000006239 protecting group Chemical group 0.000 description 4
• 239000011541 reaction mixture Substances 0.000 description 4
• 238000006467 substitution reaction Methods 0.000 description 4
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Chemical compound C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 3
• CKPNVNAKQGYUSK-UHFFFAOYSA-N 4,6-dichloropyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1Cl CKPNVNAKQGYUSK-UHFFFAOYSA-N 0.000 description 3
• QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
• 101100481408 Danio rerio tie2 gene Proteins 0.000 description 3
• 102000004190 Enzymes Human genes 0.000 description 3
• 108090000790 Enzymes Proteins 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 101100481410 Mus musculus Tek gene Proteins 0.000 description 3
• KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 3
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
• 239000013543 active substance Substances 0.000 description 3
• 125000004423 acyloxy group Chemical group 0.000 description 3
• 239000008346 aqueous phase Substances 0.000 description 3
• 239000011324 bead Substances 0.000 description 3
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
• 229910052796 boron Inorganic materials 0.000 description 3
• 210000000481 breast Anatomy 0.000 description 3
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
• 239000003054 catalyst Substances 0.000 description 3
• 238000005859 coupling reaction Methods 0.000 description 3
• 125000000000 cycloalkoxy group Chemical group 0.000 description 3
• 150000004985 diamines Chemical class 0.000 description 3
• 239000006260 foam Substances 0.000 description 3
• 239000012458 free base Substances 0.000 description 3
• 239000001963 growth medium Substances 0.000 description 3
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• 239000012299 nitrogen atmosphere Substances 0.000 description 3
• 239000012071 phase Substances 0.000 description 3
• 229910000027 potassium carbonate Inorganic materials 0.000 description 3
• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 3
• 102000004169 proteins and genes Human genes 0.000 description 3
• 108090000623 proteins and genes Proteins 0.000 description 3
• 229910000029 sodium carbonate Inorganic materials 0.000 description 3
• KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical class [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
• 230000001225 therapeutic effect Effects 0.000 description 3
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
• 238000011200 topical administration Methods 0.000 description 3
• 238000001665 trituration Methods 0.000 description 3
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical group C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 2
• LXFNLRHJSUSBFL-UHFFFAOYSA-N 1-(pyridin-2-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=N1 LXFNLRHJSUSBFL-UHFFFAOYSA-N 0.000 description 2
• BTNPJMNKYNWUPD-UHFFFAOYSA-N 1-[(3-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC(F)=C1 BTNPJMNKYNWUPD-UHFFFAOYSA-N 0.000 description 2
• VHWVWFPJTDRKIK-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=C(F)C=C1 VHWVWFPJTDRKIK-UHFFFAOYSA-N 0.000 description 2
• MACVPLPBEJHWHK-UHFFFAOYSA-N 1-benzyl-3-methyl-5-nitroindazole Chemical compound C12=CC=C([N+]([O-])=O)C=C2C(C)=NN1CC1=CC=CC=C1 MACVPLPBEJHWHK-UHFFFAOYSA-N 0.000 description 2
• LONPVIGEVNTHTN-UHFFFAOYSA-N 1-benzyl-5-nitroindole Chemical compound C1=CC2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 LONPVIGEVNTHTN-UHFFFAOYSA-N 0.000 description 2
• MXUBFGQYIZXEOV-UHFFFAOYSA-N 1-benzylindazol-5-amine;1-benzyl-5-nitroindazole Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1.N1=CC2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 MXUBFGQYIZXEOV-UHFFFAOYSA-N 0.000 description 2
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 2
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 2
• XZNGFDIIMTUDLO-UHFFFAOYSA-N 2-(4-chloropyrido[3,4-d]pyrimidin-6-yl)-5-methyl-1,3,4-oxadiazole Chemical compound O1C(C)=NN=C1C1=CC2=C(Cl)N=CN=C2C=N1 XZNGFDIIMTUDLO-UHFFFAOYSA-N 0.000 description 2
• AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 2
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
• MQTBODNTRQAUSK-UHFFFAOYSA-N 2-benzyl-3h-benzimidazol-5-amine Chemical compound N1C2=CC(N)=CC=C2N=C1CC1=CC=CC=C1 MQTBODNTRQAUSK-UHFFFAOYSA-N 0.000 description 2
• UMWIVOZCYNITGG-UHFFFAOYSA-N 2-benzyl-6-nitro-1h-benzimidazole Chemical compound N1C2=CC([N+](=O)[O-])=CC=C2N=C1CC1=CC=CC=C1 UMWIVOZCYNITGG-UHFFFAOYSA-N 0.000 description 2
• SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 2
• AMYYUKGKCJKCBI-UHFFFAOYSA-N 2-methylsulfonylethanamine;hydrochloride Chemical compound Cl.CS(=O)(=O)CCN AMYYUKGKCJKCBI-UHFFFAOYSA-N 0.000 description 2
• 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
• OZFPSOBLQZPIAV-UHFFFAOYSA-N 5-nitro-1h-indole Chemical compound [O-][N+](=O)C1=CC=C2NC=CC2=C1 OZFPSOBLQZPIAV-UHFFFAOYSA-N 0.000 description 2
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
• 239000005695 Ammonium acetate Substances 0.000 description 2
• 208000023275 Autoimmune disease Diseases 0.000 description 2
• KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
• 101150041968 CDC13 gene Proteins 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 101150008206 Cilk1 gene Proteins 0.000 description 2
• 101100503636 Danio rerio fyna gene Proteins 0.000 description 2
• 102000001301 EGF receptor Human genes 0.000 description 2
• 101150018272 FYN gene Proteins 0.000 description 2
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
• 206010020751 Hypersensitivity Diseases 0.000 description 2
• 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 2
• SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 2
• HDJLSECJEQSPKW-UHFFFAOYSA-N Methyl 2-Furancarboxylate Chemical compound COC(=O)C1=CC=CO1 HDJLSECJEQSPKW-UHFFFAOYSA-N 0.000 description 2
• OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 2
• UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
• 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 2
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 description 2
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• 150000007513 acids Chemical class 0.000 description 2
• 239000000443 aerosol Substances 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 208000026935 allergic disease Diseases 0.000 description 2
• 230000007815 allergy Effects 0.000 description 2
• 235000019257 ammonium acetate Nutrition 0.000 description 2
• 229940043376 ammonium acetate Drugs 0.000 description 2
• 230000001093 anti-cancer Effects 0.000 description 2
• 239000007864 aqueous solution Substances 0.000 description 2
• 208000006673 asthma Diseases 0.000 description 2
• 125000005605 benzo group Chemical group 0.000 description 2
• 239000008280 blood Substances 0.000 description 2
• 210000004369 blood Anatomy 0.000 description 2
• 230000037396 body weight Effects 0.000 description 2
• 125000001246 bromo group Chemical group Br* 0.000 description 2
• 125000001589 carboacyl group Chemical group 0.000 description 2
• 150000001721 carbon Chemical group 0.000 description 2
• 239000001569 carbon dioxide Substances 0.000 description 2
• 229910002092 carbon dioxide Inorganic materials 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
• 238000001516 cell proliferation assay Methods 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 238000002425 crystallisation Methods 0.000 description 2
• 125000000753 cycloalkyl group Chemical group 0.000 description 2
• NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
• 230000001419 dependent effect Effects 0.000 description 2
• SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
• IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 2
• 239000006196 drop Substances 0.000 description 2
• 239000000839 emulsion Substances 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 238000003818 flash chromatography Methods 0.000 description 2
• 235000019256 formaldehyde Nutrition 0.000 description 2
• 230000002496 gastric effect Effects 0.000 description 2
• 239000000499 gel Substances 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 201000010536 head and neck cancer Diseases 0.000 description 2
• 208000014829 head and neck neoplasm Diseases 0.000 description 2
• 150000004678 hydrides Chemical class 0.000 description 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 2
• 150000002460 imidazoles Chemical class 0.000 description 2
• 238000011534 incubation Methods 0.000 description 2
• 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 125000000842 isoxazolyl group Chemical group 0.000 description 2
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
• 244000005700 microbiome Species 0.000 description 2
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 2
• 239000002674 ointment Substances 0.000 description 2
• 239000012074 organic phase Substances 0.000 description 2
• 230000002611 ovarian Effects 0.000 description 2
• 230000002018 overexpression Effects 0.000 description 2
• QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 2
• 239000006072 paste Substances 0.000 description 2
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
• 238000003566 phosphorylation assay Methods 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
• 108090000765 processed proteins & peptides Proteins 0.000 description 2
• PZURVUQVDFSJJO-UHFFFAOYSA-N pyrimidine-4,6-diamine Chemical compound NC1=CC(N)=N[C]=N1 PZURVUQVDFSJJO-UHFFFAOYSA-N 0.000 description 2
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
• 102000005962 receptors Human genes 0.000 description 2
• 108020003175 receptors Proteins 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 238000006722 reduction reaction Methods 0.000 description 2
• 238000006268 reductive amination reaction Methods 0.000 description 2
• 230000002829 reductive effect Effects 0.000 description 2
• 230000021014 regulation of cell growth Effects 0.000 description 2
• 238000011160 research Methods 0.000 description 2
• 208000037803 restenosis Diseases 0.000 description 2
• 206010039073 rheumatoid arthritis Diseases 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 238000010898 silica gel chromatography Methods 0.000 description 2
• NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 2
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
• 235000017557 sodium bicarbonate Nutrition 0.000 description 2
• 239000012312 sodium hydride Substances 0.000 description 2
• 229910000104 sodium hydride Inorganic materials 0.000 description 2
• 239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
• 241000894007 species Species 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 238000010561 standard procedure Methods 0.000 description 2
• 229910000080 stannane Inorganic materials 0.000 description 2
• 239000012258 stirred mixture Substances 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 239000000758 substrate Substances 0.000 description 2
• 239000003826 tablet Substances 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• 125000003396 thiol group Chemical class [H]S* 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 2
• 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 2
• XSQUKJJJFZCRTK-UHFFFAOYSA-N urea group Chemical group NC(=O)N XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
• 229910052720 vanadium Inorganic materials 0.000 description 2
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
• NLQMSBJFLQPLIJ-UHFFFAOYSA-N (3-methyloxetan-3-yl)methanol Chemical compound OCC1(C)COC1 NLQMSBJFLQPLIJ-UHFFFAOYSA-N 0.000 description 1
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
• 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
• 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 description 1
• IMLSAISZLJGWPP-UHFFFAOYSA-N 1,3-dithiolane Chemical compound C1CSCS1 IMLSAISZLJGWPP-UHFFFAOYSA-N 0.000 description 1
• BCXOSCQTHVTUET-UHFFFAOYSA-N 1-(2-fluoro-5-nitrophenyl)ethanone Chemical compound CC(=O)C1=CC([N+]([O-])=O)=CC=C1F BCXOSCQTHVTUET-UHFFFAOYSA-N 0.000 description 1
• BHOSCKKNURHTND-UHFFFAOYSA-N 1-(benzenesulfonyl)indol-5-amine Chemical compound C1=CC2=CC(N)=CC=C2N1S(=O)(=O)C1=CC=CC=C1 BHOSCKKNURHTND-UHFFFAOYSA-N 0.000 description 1
• ZSFTXNIYPDDDSG-UHFFFAOYSA-N 1-(pyridin-3-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CN=C1 ZSFTXNIYPDDDSG-UHFFFAOYSA-N 0.000 description 1
• JXYVDGXOCFQXTF-UHFFFAOYSA-N 1-(pyridin-4-ylmethyl)indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=NC=C1 JXYVDGXOCFQXTF-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• DDCMQWDHBVDKHH-UHFFFAOYSA-N 1-[(2,3-difluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC(F)=C1F DDCMQWDHBVDKHH-UHFFFAOYSA-N 0.000 description 1
• HNAXFSKDGWBXFI-UHFFFAOYSA-N 1-[(2-fluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC=CC=C1F HNAXFSKDGWBXFI-UHFFFAOYSA-N 0.000 description 1
• DRTQHJPVMGBUCF-UCVXFZOQSA-N 1-[(2s,3s,4s,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@H]1[C@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UCVXFZOQSA-N 0.000 description 1
• ZEGHCBNPNZAANE-UHFFFAOYSA-N 1-[(3,5-difluorophenyl)methyl]indazol-5-amine Chemical compound N1=CC2=CC(N)=CC=C2N1CC1=CC(F)=CC(F)=C1 ZEGHCBNPNZAANE-UHFFFAOYSA-N 0.000 description 1
• 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 description 1
• NCALXEWOPBPBQR-UHFFFAOYSA-N 1-benzyl-3-methylindazol-5-amine Chemical compound C12=CC=C(N)C=C2C(C)=NN1CC1=CC=CC=C1 NCALXEWOPBPBQR-UHFFFAOYSA-N 0.000 description 1
• QRBOICRSKLIRGU-UHFFFAOYSA-N 1-benzyl-3-methylindazol-5-amine;1-benzyl-3-methyl-5-nitroindazole Chemical compound C12=CC=C(N)C=C2C(C)=NN1CC1=CC=CC=C1.C12=CC=C([N+]([O-])=O)C=C2C(C)=NN1CC1=CC=CC=C1 QRBOICRSKLIRGU-UHFFFAOYSA-N 0.000 description 1
• KACWEIWGSHNESJ-UHFFFAOYSA-N 1-benzyl-5-nitroindazole Chemical compound N1=CC2=CC([N+](=O)[O-])=CC=C2N1CC1=CC=CC=C1 KACWEIWGSHNESJ-UHFFFAOYSA-N 0.000 description 1
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• YDTDKKULPWTHRV-UHFFFAOYSA-N 1H-indazol-3-amine Chemical compound C1=CC=C2C(N)=NNC2=C1 YDTDKKULPWTHRV-UHFFFAOYSA-N 0.000 description 1
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
• GPWNWKWQOLEVEQ-UHFFFAOYSA-N 2,4-diaminopyrimidine-5-carbaldehyde Chemical compound NC1=NC=C(C=O)C(N)=N1 GPWNWKWQOLEVEQ-UHFFFAOYSA-N 0.000 description 1
• SRLUJNCPQPGUKZ-UHFFFAOYSA-N 2-(dimethylamino)-5-(2,2-dimethylpropanoylamino)pyridine-4-carboxylic acid Chemical compound CN(C)C1=CC(C(O)=O)=C(NC(=O)C(C)(C)C)C=N1 SRLUJNCPQPGUKZ-UHFFFAOYSA-N 0.000 description 1
• IMSODMZESSGVBE-UHFFFAOYSA-N 2-Oxazoline Chemical compound C1CN=CO1 IMSODMZESSGVBE-UHFFFAOYSA-N 0.000 description 1
• 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 1
• KNDAEDDIIQYRHY-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-(piperazin-1-ylmethyl)pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)CN1CCNCC1 KNDAEDDIIQYRHY-UHFFFAOYSA-N 0.000 description 1
• LUKTXELAICAZNV-UHFFFAOYSA-N 2-[[2-(methanesulfonamido)ethylamino]-[(3-methylsulfinylpropylamino)methyl]amino]acetamide Chemical compound CS(=O)CCCNCN(CC(N)=O)NCCNS(C)(=O)=O LUKTXELAICAZNV-UHFFFAOYSA-N 0.000 description 1
• WOBMUXLADQPSBY-UHFFFAOYSA-N 2-benzyl-5-nitro-1,3-dihydroindazole Chemical compound C1C2=CC([N+](=O)[O-])=CC=C2NN1CC1=CC=CC=C1 WOBMUXLADQPSBY-UHFFFAOYSA-N 0.000 description 1
• LIEPVGBDUYKPLC-UHFFFAOYSA-N 2-chloro-4-nitropyridine Chemical compound [O-][N+](=O)C1=CC=NC(Cl)=C1 LIEPVGBDUYKPLC-UHFFFAOYSA-N 0.000 description 1
• VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 1
• MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
• 125000001698 2H-pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical compound O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 0.000 description 1
• RNUNUPZAHSFZPH-UHFFFAOYSA-N 3-(benzenesulfonyl)-1h-indol-6-amine Chemical compound C=1NC2=CC(N)=CC=C2C=1S(=O)(=O)C1=CC=CC=C1 RNUNUPZAHSFZPH-UHFFFAOYSA-N 0.000 description 1
• KQAODTJBTYIOOT-UHFFFAOYSA-N 3-(benzenesulfonyl)-6-nitro-1h-indole Chemical compound C=1NC2=CC([N+](=O)[O-])=CC=C2C=1S(=O)(=O)C1=CC=CC=C1 KQAODTJBTYIOOT-UHFFFAOYSA-N 0.000 description 1
• OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
• PQVHMOLNSYFXIJ-UHFFFAOYSA-N 4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]pyrazole-3-carboxylic acid Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(N1CC2=C(CC1)NN=N2)=O)C(=O)O PQVHMOLNSYFXIJ-UHFFFAOYSA-N 0.000 description 1
• FNYGYUJHUMLFKN-UHFFFAOYSA-N 4-chloro-6-phenylmethoxypyrido[3,4-d]pyrimidine hydrochloride Chemical compound C1=CC=C(C=C1)COC2=NC=C3C(=C2)C(=NC=N3)Cl.Cl FNYGYUJHUMLFKN-UHFFFAOYSA-N 0.000 description 1
• DBPKMSBWOKAKLA-UHFFFAOYSA-N 4-chloropyrimidine Chemical compound ClC1=CC=NC=N1 DBPKMSBWOKAKLA-UHFFFAOYSA-N 0.000 description 1
• HGWZRWMSONEISS-UHFFFAOYSA-N 4-n-(3-benzyl-2h-indazol-6-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1NN=2)=CC=C1C=2CC1=CC=CC=C1 HGWZRWMSONEISS-UHFFFAOYSA-N 0.000 description 1
• MXZQLVOKPYMZSH-UHFFFAOYSA-N 4-n-(3-benzylsulfonyl-2h-indazol-6-yl)-6-n,6-n-dimethylpyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N(C)C)=CC2=C1NC(C=C1NN=2)=CC=C1C=2S(=O)(=O)CC1=CC=CC=C1 MXZQLVOKPYMZSH-UHFFFAOYSA-N 0.000 description 1
• RAUWPNXIALNKQM-UHFFFAOYSA-N 4-nitro-1,2-phenylenediamine Chemical compound NC1=CC=C([N+]([O-])=O)C=C1N RAUWPNXIALNKQM-UHFFFAOYSA-N 0.000 description 1
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
• PEXVJBCQKQZYOI-UHFFFAOYSA-N 5-amino-2-(dimethylamino)pyridine-4-carboxylic acid Chemical compound CN(C)C1=CC(C(O)=O)=C(N)C=N1 PEXVJBCQKQZYOI-UHFFFAOYSA-N 0.000 description 1
• IJIBRSFAXRFPPN-UHFFFAOYSA-N 5-bromo-2-methoxybenzaldehyde Chemical compound COC1=CC=C(Br)C=C1C=O IJIBRSFAXRFPPN-UHFFFAOYSA-N 0.000 description 1
• NEGMMKYAVYNLCG-UHFFFAOYSA-N 5-ethyl-1-methyl-5-phenylimidazolidine-2,4-dione Chemical compound C=1C=CC=CC=1C1(CC)N(C)C(=O)NC1=O NEGMMKYAVYNLCG-UHFFFAOYSA-N 0.000 description 1
• WSGURAYTCUVDQL-UHFFFAOYSA-N 5-nitro-1h-indazole Chemical compound [O-][N+](=O)C1=CC=C2NN=CC2=C1 WSGURAYTCUVDQL-UHFFFAOYSA-N 0.000 description 1
• UAWMVMPAYRWUFX-UHFFFAOYSA-N 6-Chloronicotinic acid Chemical compound OC(=O)C1=CC=C(Cl)N=C1 UAWMVMPAYRWUFX-UHFFFAOYSA-N 0.000 description 1
• NUTUPYCNXAFILA-UHFFFAOYSA-N 6-chloro-1h-pyrido[3,4-d]pyrimidin-2-one Chemical compound C1=NC(=O)NC2=C1C=C(Cl)N=C2 NUTUPYCNXAFILA-UHFFFAOYSA-N 0.000 description 1
• BBPUOYYUBFLNML-UHFFFAOYSA-N 6-chloro-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound N1=CNC(=O)C2=C1C=NC(Cl)=C2 BBPUOYYUBFLNML-UHFFFAOYSA-N 0.000 description 1
• OGOPAVRSPJYRLS-UHFFFAOYSA-N 6-chloropyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC(Cl)=CC2=C1 OGOPAVRSPJYRLS-UHFFFAOYSA-N 0.000 description 1
• IMVBSHGHRSHNOT-UHFFFAOYSA-N 6-phenylmethoxy-1h-pyrido[3,4-d]pyrimidin-4-one Chemical compound C1=C2C(=O)NC=NC2=CN=C1OCC1=CC=CC=C1 IMVBSHGHRSHNOT-UHFFFAOYSA-N 0.000 description 1
• 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 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 239000004342 Benzoyl peroxide Substances 0.000 description 1
• OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 description 1
• UBTWOTPEXONAKG-UHFFFAOYSA-N CS(CCN)(=O)=O.OC(C1=CC=C(C(N=C2)=CC3=C2N=CN=C3NC2=CC=C3N(CC4=CC=CC=C4)N=CC3=C2)O1)=O.Cl.Cl Chemical compound CS(CCN)(=O)=O.OC(C1=CC=C(C(N=C2)=CC3=C2N=CN=C3NC2=CC=C3N(CC4=CC=CC=C4)N=CC3=C2)O1)=O.Cl.Cl UBTWOTPEXONAKG-UHFFFAOYSA-N 0.000 description 1
• 206010009944 Colon cancer Diseases 0.000 description 1
• 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
• 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 1
• 241000792859 Enema Species 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 239000007995 HEPES buffer Substances 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 239000007836 KH2PO4 Substances 0.000 description 1
• 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
• 102100028123 Macrophage colony-stimulating factor 1 Human genes 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
• 108091008606 PDGF receptors Proteins 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 241000282320 Panthera leo Species 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 102000001253 Protein Kinase Human genes 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 239000007868 Raney catalyst Substances 0.000 description 1
• NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 1
• 229910000564 Raney nickel Inorganic materials 0.000 description 1
• 108091005682 Receptor kinases Proteins 0.000 description 1
• 241000320554 Streptomyces rimosus subsp. paromomycinus Species 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 206010052779 Transplant rejections Diseases 0.000 description 1
• GCTFWCDSFPMHHS-UHFFFAOYSA-M Tributyltin chloride Chemical compound CCCC[Sn](Cl)(CCCC)CCCC GCTFWCDSFPMHHS-UHFFFAOYSA-M 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 238000002835 absorbance Methods 0.000 description 1
• 229960000583 acetic acid Drugs 0.000 description 1
• XPOLVIIHTDKJRY-UHFFFAOYSA-N acetic acid;methanimidamide Chemical compound NC=N.CC(O)=O XPOLVIIHTDKJRY-UHFFFAOYSA-N 0.000 description 1
• 238000005903 acid hydrolysis reaction Methods 0.000 description 1
• 230000002378 acidificating effect Effects 0.000 description 1
• 230000009471 action Effects 0.000 description 1
• 230000004913 activation Effects 0.000 description 1
• 238000007259 addition reaction Methods 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 150000001299 aldehydes Chemical group 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000002355 alkine group Chemical group 0.000 description 1
• 125000000033 alkoxyamino group Chemical group 0.000 description 1
• 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 description 1
• 125000003368 amide group Chemical group 0.000 description 1
• 125000000320 amidine group Chemical group 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 150000008064 anhydrides Chemical class 0.000 description 1
• 125000003705 anilinocarbonyl group Chemical group O=C([*])N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• 238000011319 anticancer therapy Methods 0.000 description 1
• 239000003963 antioxidant agent Substances 0.000 description 1
• 235000006708 antioxidants Nutrition 0.000 description 1
• 239000000010 aprotic solvent Substances 0.000 description 1
• 239000006286 aqueous extract Substances 0.000 description 1
• 239000003125 aqueous solvent Substances 0.000 description 1
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
• 125000003710 aryl alkyl group Chemical group 0.000 description 1
• 125000005418 aryl aryl group Chemical group 0.000 description 1
• 150000001502 aryl halides Chemical class 0.000 description 1
• 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
• 125000005110 aryl thio group Chemical group 0.000 description 1
• 125000004104 aryloxy group Chemical group 0.000 description 1
• 150000001540 azides Chemical class 0.000 description 1
• 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• 235000019400 benzoyl peroxide Nutrition 0.000 description 1
• 235000019445 benzyl alcohol Nutrition 0.000 description 1
• MSJHOJKVMMEMNX-UHFFFAOYSA-N benzylhydrazine;hydron;dichloride Chemical compound Cl.Cl.NNCC1=CC=CC=C1 MSJHOJKVMMEMNX-UHFFFAOYSA-N 0.000 description 1
• 230000005540 biological transmission Effects 0.000 description 1
• 201000011263 bladder neck cancer Diseases 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 201000008275 breast carcinoma Diseases 0.000 description 1
• 210000000069 breast epithelial cell Anatomy 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 239000006227 byproduct Substances 0.000 description 1
• 229940041514 candida albicans extract Drugs 0.000 description 1
• 239000002775 capsule Substances 0.000 description 1
• 239000004202 carbamide Substances 0.000 description 1
• XEVRDFDBXJMZFG-UHFFFAOYSA-N carbonyl dihydrazine Chemical compound NNC(=O)NN XEVRDFDBXJMZFG-UHFFFAOYSA-N 0.000 description 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
• 150000007942 carboxylates Chemical class 0.000 description 1
• 125000002843 carboxylic acid group Chemical group 0.000 description 1
• 230000010261 cell growth Effects 0.000 description 1
• 210000000170 cell membrane Anatomy 0.000 description 1
• 238000012512 characterization method Methods 0.000 description 1
• SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical group C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 1
• 239000003638 chemical reducing agent Substances 0.000 description 1
• 230000000973 chemotherapeutic effect Effects 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 210000001072 colon Anatomy 0.000 description 1
• 238000004440 column chromatography Methods 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
• LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
• 230000002338 cryopreservative effect Effects 0.000 description 1
• 239000013078 crystal Substances 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
• 125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000006317 cyclopropyl amino group Chemical group 0.000 description 1
• 230000001627 detrimental effect Effects 0.000 description 1
• 239000002027 dichloromethane extract Substances 0.000 description 1
• 125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• 238000004821 distillation Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000003480 eluent Substances 0.000 description 1
• 239000007920 enema Substances 0.000 description 1
• 229940079360 enema for constipation Drugs 0.000 description 1
• 210000002615 epidermis Anatomy 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 1
• LIWAQLJGPBVORC-UHFFFAOYSA-N ethylmethylamine Chemical compound CCNC LIWAQLJGPBVORC-UHFFFAOYSA-N 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 239000003889 eye drop Substances 0.000 description 1
• 229940012356 eye drops Drugs 0.000 description 1
• 229960004979 fampridine Drugs 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000010419 fine particle Substances 0.000 description 1
• 239000000796 flavoring agent Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000013355 food flavoring agent Nutrition 0.000 description 1
• 235000019253 formic acid Nutrition 0.000 description 1
• LAULFZIZDHINAX-UHFFFAOYSA-N furan-2-carboxylic acid Chemical compound OC(=O)C1=CC=CO1.OC(=O)C1=CC=CO1 LAULFZIZDHINAX-UHFFFAOYSA-N 0.000 description 1
• 125000002541 furyl group Chemical group 0.000 description 1
• 230000008570 general process Effects 0.000 description 1
• 239000012362 glacial acetic acid Substances 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 239000003102 growth factor Substances 0.000 description 1
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
• 229940093915 gynecological organic acid Drugs 0.000 description 1
• 125000001188 haloalkyl group Chemical group 0.000 description 1
• 150000008282 halocarbons Chemical class 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 150000002391 heterocyclic compounds Chemical class 0.000 description 1
• 230000003054 hormonal effect Effects 0.000 description 1
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• 150000003840 hydrochlorides Chemical class 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 239000008309 hydrophilic cream Substances 0.000 description 1
• 125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
• JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 239000012442 inert solvent Substances 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 230000002401 inhibitory effect Effects 0.000 description 1
• 230000000977 initiatory effect Effects 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 238000007918 intramuscular administration Methods 0.000 description 1
• 238000001990 intravenous administration Methods 0.000 description 1
• 125000002346 iodo group Chemical group I* 0.000 description 1
• 238000005040 ion trap Methods 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 150000002576 ketones Chemical class 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
• 239000006210 lotion Substances 0.000 description 1
• 239000007937 lozenge Substances 0.000 description 1
• 210000004072 lung Anatomy 0.000 description 1
• 230000014759 maintenance of location Effects 0.000 description 1
• 238000001819 mass spectrum Methods 0.000 description 1
• 238000013160 medical therapy Methods 0.000 description 1
• HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 description 1
• 125000006178 methyl benzyl group Chemical group 0.000 description 1
• CXKWCBBOMKCUKX-UHFFFAOYSA-M methylene blue Chemical compound [Cl-].C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 CXKWCBBOMKCUKX-UHFFFAOYSA-M 0.000 description 1
• 229960000907 methylthioninium chloride Drugs 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
• 235000019796 monopotassium phosphate Nutrition 0.000 description 1
• 230000000877 morphologic effect Effects 0.000 description 1
• 239000002324 mouth wash Substances 0.000 description 1
• 230000035772 mutation Effects 0.000 description 1
• RNCGDMXTBBJFEB-UHFFFAOYSA-N n-(1-benzylindazol-5-yl)-6-[5-(1-methyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)furan-2-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound O1CC(C)(CO2)COC12C(O1)=CC=C1C(N=CC1=NC=N2)=CC1=C2NC(C=C1C=N2)=CC=C1N2CC1=CC=CC=C1 RNCGDMXTBBJFEB-UHFFFAOYSA-N 0.000 description 1
• PDUSWJORWQPNRP-UHFFFAOYSA-N n-propan-2-ylacetamide Chemical compound CC(C)NC(C)=O PDUSWJORWQPNRP-UHFFFAOYSA-N 0.000 description 1
• 150000005054 naphthyridines Chemical class 0.000 description 1
• 239000007923 nasal drop Substances 0.000 description 1
• 229940100662 nasal drops Drugs 0.000 description 1
• 229940097496 nasal spray Drugs 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 238000006386 neutralization reaction Methods 0.000 description 1
• 150000002825 nitriles Chemical class 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• 238000011369 optimal treatment Methods 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 210000001672 ovary Anatomy 0.000 description 1
• 125000003585 oxepinyl group Chemical group 0.000 description 1
• 239000007800 oxidant agent Substances 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• 230000001590 oxidative effect Effects 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 230000036961 partial effect Effects 0.000 description 1
• 239000002245 particle Substances 0.000 description 1
• 235000010603 pastilles Nutrition 0.000 description 1
• 239000008188 pellet Substances 0.000 description 1
• 150000002978 peroxides Chemical class 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 229960003424 phenylacetic acid Drugs 0.000 description 1
• 239000003279 phenylacetic acid 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
• 239000010452 phosphate Substances 0.000 description 1
• RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
• 230000026731 phosphorylation Effects 0.000 description 1
• 238000006366 phosphorylation reaction Methods 0.000 description 1
• 102000020233 phosphotransferase Human genes 0.000 description 1
• DCWXELXMIBXGTH-UHFFFAOYSA-N phosphotyrosine Chemical compound OC(=O)C(N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-UHFFFAOYSA-N 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 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
• 239000004810 polytetrafluoroethylene Substances 0.000 description 1
• 229920001343 polytetrafluoroethylene Polymers 0.000 description 1
• GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 238000002953 preparative HPLC Methods 0.000 description 1
• 230000002035 prolonged effect Effects 0.000 description 1
• 230000000069 prophylactic effect Effects 0.000 description 1
• 108060006633 protein kinase Proteins 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 1
• PAQYIEZTLSDLQO-UHFFFAOYSA-N pyrido[3,4-d]pyrimidine Chemical compound N1=CN=C2C=NC=CC2=C1 PAQYIEZTLSDLQO-UHFFFAOYSA-N 0.000 description 1
• 150000008518 pyridopyrimidines Chemical class 0.000 description 1
• 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
• 150000003230 pyrimidines Chemical class 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• 230000009703 regulation of cell differentiation Effects 0.000 description 1
• 230000010076 replication Effects 0.000 description 1
• 210000002966 serum Anatomy 0.000 description 1
• 229910001923 silver oxide Inorganic materials 0.000 description 1
• 210000003491 skin Anatomy 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
• 229910052938 sodium sulfate Inorganic materials 0.000 description 1
• 235000011152 sodium sulphate Nutrition 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 125000005415 substituted alkoxy group Chemical group 0.000 description 1
• 125000000547 substituted alkyl group Chemical group 0.000 description 1
• FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 239000006228 supernatant Substances 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 239000000375 suspending agent Substances 0.000 description 1
• IXXMVXXFAJGOQO-YFKPBYRVSA-N tert-butyl (2s)-2-hydroxypropanoate Chemical compound C[C@H](O)C(=O)OC(C)(C)C IXXMVXXFAJGOQO-YFKPBYRVSA-N 0.000 description 1
• 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
• 125000005306 thianaphthenyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 125000003777 thiepinyl group Chemical group 0.000 description 1
• 238000004809 thin layer chromatography Methods 0.000 description 1
• 229940100611 topical cream Drugs 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 229940100615 topical ointment Drugs 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 238000012546 transfer Methods 0.000 description 1
• 238000002054 transplantation Methods 0.000 description 1
• SANWDQJIWZEKOD-UHFFFAOYSA-N tributyl(furan-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=CO1 SANWDQJIWZEKOD-UHFFFAOYSA-N 0.000 description 1
• ROQMYQHKJMRTPC-UHFFFAOYSA-N tributyl-[5-(1,3-dioxolan-2-ylmethyl)furan-2-yl]stannane Chemical compound O1C([Sn](CCCC)(CCCC)CCCC)=CC=C1CC1OCCO1 ROQMYQHKJMRTPC-UHFFFAOYSA-N 0.000 description 1
• DMOYILRVNNYQTM-UHFFFAOYSA-N tributyl-[5-(1-methyl-3,5,8-trioxabicyclo[2.2.2]octan-4-yl)furan-2-yl]stannane Chemical compound O1C([Sn](CCCC)(CCCC)CCCC)=CC=C1C1(OC2)OCC2(C)CO1 DMOYILRVNNYQTM-UHFFFAOYSA-N 0.000 description 1
• UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
• 210000004881 tumor cell Anatomy 0.000 description 1
• 230000000381 tumorigenic effect Effects 0.000 description 1
• 241000701447 unidentified baculovirus Species 0.000 description 1
• PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
• 238000005406 washing Methods 0.000 description 1
• 239000008215 water for injection Substances 0.000 description 1
• 239000012138 yeast extract Substances 0.000 description 1