PT2486039T - Derivados de purina úteis como inibidores de hsp90 - Google Patents
Derivados de purina úteis como inibidores de hsp90 Download PDFInfo
- Publication number
- PT2486039T PT2486039T PT108227182T PT10822718T PT2486039T PT 2486039 T PT2486039 T PT 2486039T PT 108227182 T PT108227182 T PT 108227182T PT 10822718 T PT10822718 T PT 10822718T PT 2486039 T PT2486039 T PT 2486039T
- Authority
- PT
- Portugal
- Prior art keywords
- purin
- dioxol
- benzo
- amine
- methyl
- Prior art date
Links
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 title description 7
- 229940083251 peripheral vasodilators purine derivative Drugs 0.000 title description 2
- 125000000561 purinyl group Chemical class N1=C(N=C2N=CNC2=C1)* 0.000 title description 2
- -1 3- (tert-butylamino) propyl Chemical group 0.000 claims description 175
- 150000001875 compounds Chemical class 0.000 claims description 94
- 239000000203 mixture Substances 0.000 claims description 73
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 44
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 40
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 claims description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 101001016865 Homo sapiens Heat shock protein HSP 90-alpha Proteins 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 28
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 22
- 125000000304 alkynyl group Chemical group 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 10
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 201000011510 cancer Diseases 0.000 claims description 9
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 7
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 6
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
- 230000004770 neurodegeneration Effects 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 150000002460 imidazoles Chemical class 0.000 claims description 5
- 230000005764 inhibitory process Effects 0.000 claims description 5
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000004122 cyclic group Chemical group 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- DIWAIIDRGJLSBT-UHFFFAOYSA-N 8-[(6-ethynyl-1,3-benzodioxol-5-yl)methyl]-2-fluoro-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N1=C(F)N=C2N(CCNCC(C)C)C(CC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N DIWAIIDRGJLSBT-UHFFFAOYSA-N 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 3
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052736 halogen Chemical group 0.000 claims description 3
- 150000002367 halogens Chemical group 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 229930192474 thiophene Natural products 0.000 claims description 3
- QOQNHOOIAFSZLG-UHFFFAOYSA-N 2-fluoro-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]methyl]-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=CC=C(C)O1 QOQNHOOIAFSZLG-UHFFFAOYSA-N 0.000 claims description 2
- JURPISZPXRJBKA-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(1h-pyrazol-5-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C=1C=CNN=1 JURPISZPXRJBKA-UHFFFAOYSA-N 0.000 claims description 2
- PVPHAJFAIFBQCT-UHFFFAOYSA-N 8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N1=CN=C2N(CCNCC(C)C)C(SC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N PVPHAJFAIFBQCT-UHFFFAOYSA-N 0.000 claims description 2
- GLEFJNSPLRHGFO-UHFFFAOYSA-N 8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N GLEFJNSPLRHGFO-UHFFFAOYSA-N 0.000 claims description 2
- NTVCUEPZZNXKEB-UHFFFAOYSA-N 8-[[6-(1,3-oxazol-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=NC=CO1 NTVCUEPZZNXKEB-UHFFFAOYSA-N 0.000 claims description 2
- QLJRQRPCWLJSFE-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCNCC(C)(C)C)C(SC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N QLJRQRPCWLJSFE-UHFFFAOYSA-N 0.000 claims description 2
- RVMVCKJTESRMPO-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[[6-(furan-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=CO1 RVMVCKJTESRMPO-UHFFFAOYSA-N 0.000 claims description 2
- AHTRRABJCYPYHD-UHFFFAOYSA-N 9-[3-(propan-2-ylamino)propyl]-8-[[6-(1,3-thiazol-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=NC=CS1 AHTRRABJCYPYHD-UHFFFAOYSA-N 0.000 claims description 2
- GBDUXJSWSYSYPX-UHFFFAOYSA-N 9-[3-(propan-2-ylamino)propyl]-8-[[6-(1h-pyrazol-5-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C=1C=CNN=1 GBDUXJSWSYSYPX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 125000006321 2-propynyl amino group Chemical group [H]C#CC([H])([H])N([H])* 0.000 claims 2
- 238000009472 formulation Methods 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical compound NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 claims 2
- KYOBNLDHDNGDTP-UHFFFAOYSA-N 1-[6-amino-8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]-3-(tert-butylamino)propan-2-ol Chemical compound N1=CN=C2N(CC(O)CNC(C)(C)C)C(SC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N KYOBNLDHDNGDTP-UHFFFAOYSA-N 0.000 claims 1
- LUCXIGJNALARSS-UHFFFAOYSA-N 1-[6-amino-8-[[6-(1h-pyrazol-5-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-9-yl]-3-(propan-2-ylamino)propan-2-ol Chemical compound N=1C2=C(N)N=CN=C2N(CC(O)CNC(C)C)C=1SC1=CC=2OCOC=2C=C1C=1C=CNN=1 LUCXIGJNALARSS-UHFFFAOYSA-N 0.000 claims 1
- DFLQFWNQYKSTDM-UHFFFAOYSA-N 1-[6-amino-8-[[6-(5-methyl-1,3-oxazol-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-9-yl]-3-(propan-2-ylamino)propan-2-ol Chemical compound N=1C2=C(N)N=CN=C2N(CC(O)CNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=NC=C(C)O1 DFLQFWNQYKSTDM-UHFFFAOYSA-N 0.000 claims 1
- HNPMBCQUWFJHSV-UHFFFAOYSA-N 1-[6-amino-8-[[6-(5-methyl-1,3-thiazol-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-9-yl]-3-(propan-2-ylamino)propan-2-ol Chemical compound N=1C2=C(N)N=CN=C2N(CC(O)CNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=NC=C(C)S1 HNPMBCQUWFJHSV-UHFFFAOYSA-N 0.000 claims 1
- CHYCJEKHDBMKHV-UHFFFAOYSA-N 1-[6-amino-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-9-yl]-3-(tert-butylamino)propan-2-ol Chemical compound O1C(C)=CC=C1C(C(=C1)SC=2N(C3=NC=NC(N)=C3N=2)CC(O)CNC(C)(C)C)=CC2=C1OCO2 CHYCJEKHDBMKHV-UHFFFAOYSA-N 0.000 claims 1
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims 1
- BBMCJNUMWBXHLH-UHFFFAOYSA-N 2-fluoro-8-[[6-(5-methyl-1,3-oxazol-2-yl)-1,3-benzodioxol-5-yl]methyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCCNC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=NC=C(C)O1 BBMCJNUMWBXHLH-UHFFFAOYSA-N 0.000 claims 1
- RCGCANBTBQGYHH-UHFFFAOYSA-N 2-fluoro-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]methyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCCNC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=CC=C(C)O1 RCGCANBTBQGYHH-UHFFFAOYSA-N 0.000 claims 1
- ZSJUKJWAPUMIJT-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(1,3-oxazol-2-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=NC=CO1 ZSJUKJWAPUMIJT-UHFFFAOYSA-N 0.000 claims 1
- NHIBVJOZVSGUSI-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(1,3-thiazol-2-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=NC=CS1 NHIBVJOZVSGUSI-UHFFFAOYSA-N 0.000 claims 1
- IZXIMXUSLRILMH-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(5-methyl-1,3-thiazol-2-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=NC=C(C)S1 IZXIMXUSLRILMH-UHFFFAOYSA-N 0.000 claims 1
- OTXQRDGXBBZEQK-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(5-methyl-1h-pyrazol-3-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C=1C=C(C)NN=1 OTXQRDGXBBZEQK-UHFFFAOYSA-N 0.000 claims 1
- VIAKABOPSDGLHQ-UHFFFAOYSA-N 3-[2-[6-amino-8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]purin-9-yl]ethylamino]-n-hydroxypropanamide Chemical compound N=1C=2C(N)=NC=NC=2N(CCNCCC(=O)NO)C=1SC(C(=C1)C#C)=CC2=C1OCO2 VIAKABOPSDGLHQ-UHFFFAOYSA-N 0.000 claims 1
- QWEIMZLTQKIJPJ-UHFFFAOYSA-N 3-[2-[6-amino-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-9-yl]ethylamino]-n-hydroxypropanamide Chemical compound O1C(C)=CC=C1C(C(=C1)SC=2N(C3=NC=NC(N)=C3N=2)CCNCCC(=O)NO)=CC2=C1OCO2 QWEIMZLTQKIJPJ-UHFFFAOYSA-N 0.000 claims 1
- YSEUPOCFWWALIE-UHFFFAOYSA-N 6-amino-8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]-9-[2-[2-(sulfamoylamino)ethylamino]ethyl]purine Chemical compound N=1C=2C(N)=NC=NC=2N(CCNCCNS(N)(=O)=O)C=1SC(C(=C1)C#C)=CC2=C1OCO2 YSEUPOCFWWALIE-UHFFFAOYSA-N 0.000 claims 1
- LYNZXCNJPUCCLG-UHFFFAOYSA-N 6-amino-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[2-[2-(sulfamoylamino)ethylamino]ethyl]purine Chemical compound O1C(C)=CC=C1C(C(=C1)SC=2N(C3=NC=NC(N)=C3N=2)CCNCCNS(N)(=O)=O)=CC2=C1OCO2 LYNZXCNJPUCCLG-UHFFFAOYSA-N 0.000 claims 1
- XTNDWQPUBZAKAQ-UHFFFAOYSA-N 8-[(6-ethynyl-1,3-benzodioxol-5-yl)methyl]-2-fluoro-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N1=C(F)N=C2N(CCCNC(C)C)C(CC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N XTNDWQPUBZAKAQ-UHFFFAOYSA-N 0.000 claims 1
- BVBDYGCBGBNELL-UHFFFAOYSA-N 8-[[6-(furan-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=CO1 BVBDYGCBGBNELL-UHFFFAOYSA-N 0.000 claims 1
- OYEPVQOGRKOZKR-UHFFFAOYSA-N 8-[[6-[5-(aminomethyl)furan-2-yl]-1,3-benzodioxol-5-yl]methyl]-2-fluoro-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=CC=C(CN)O1 OYEPVQOGRKOZKR-UHFFFAOYSA-N 0.000 claims 1
- ZNOVAEUSSJLCQP-UHFFFAOYSA-N 8-[[6-[5-(aminomethyl)furan-2-yl]-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=C(CN)O1 ZNOVAEUSSJLCQP-UHFFFAOYSA-N 0.000 claims 1
- YMCCRIPIFPZVNP-UHFFFAOYSA-N 9-(2-aminoethyl)-8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCN)C(SC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N YMCCRIPIFPZVNP-UHFFFAOYSA-N 0.000 claims 1
- XQBKHKKZKKQGRL-UHFFFAOYSA-N 9-(3-aminopropyl)-2-fluoro-8-[[6-(5-methyl-1,3-oxazol-2-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound O1C(C)=CN=C1C(C(=C1)CC=2N(C3=NC(F)=NC(N)=C3N=2)CCCN)=CC2=C1OCO2 XQBKHKKZKKQGRL-UHFFFAOYSA-N 0.000 claims 1
- NGNPZPJEDHRLKG-UHFFFAOYSA-N 9-(3-aminopropyl)-2-fluoro-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound O1C(C)=CC=C1C(C(=C1)CC=2N(C3=NC(F)=NC(N)=C3N=2)CCCN)=CC2=C1OCO2 NGNPZPJEDHRLKG-UHFFFAOYSA-N 0.000 claims 1
- QQHIGNMBSRXHTL-UHFFFAOYSA-N 9-(3-aminopropyl)-8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCCN)C(SC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N QQHIGNMBSRXHTL-UHFFFAOYSA-N 0.000 claims 1
- NGNUZXGUPOZTPJ-UHFFFAOYSA-N 9-(3-aminopropyl)-8-[[6-(1h-pyrazol-5-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCN)C=1SC1=CC=2OCOC=2C=C1C=1C=CNN=1 NGNUZXGUPOZTPJ-UHFFFAOYSA-N 0.000 claims 1
- JNTKGRLJXXBCSQ-UHFFFAOYSA-N 9-(3-aminopropyl)-8-[[6-(5-methyl-1,3-oxazol-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound O1C(C)=CN=C1C(C(=C1)SC=2N(C3=NC=NC(N)=C3N=2)CCCN)=CC2=C1OCO2 JNTKGRLJXXBCSQ-UHFFFAOYSA-N 0.000 claims 1
- DQAPABBROHQZKS-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(6-ethynyl-1,3-benzodioxol-5-yl)methyl]-2-fluoropurin-6-amine Chemical compound N1=C(F)N=C2N(CCNCC(C)(C)C)C(CC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N DQAPABBROHQZKS-UHFFFAOYSA-N 0.000 claims 1
- YNUVMGFURSKOEO-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[[6-(5-methyl-1,3-oxazol-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound O1C(C)=CN=C1C(C(=C1)SC=2N(C3=NC=NC(N)=C3N=2)CCNCC(C)(C)C)=CC2=C1OCO2 YNUVMGFURSKOEO-UHFFFAOYSA-N 0.000 claims 1
- HXHVNWFMEFLYSY-UHFFFAOYSA-N 9-[3-(tert-butylamino)propyl]-2-fluoro-8-[[6-(1,3-oxazol-2-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCCNC(C)(C)C)C=1CC1=CC=2OCOC=2C=C1C1=NC=CO1 HXHVNWFMEFLYSY-UHFFFAOYSA-N 0.000 claims 1
- MCINGXDOYPFFSW-UHFFFAOYSA-N 9-[3-(tert-butylamino)propyl]-2-fluoro-8-[[6-(1h-pyrazol-5-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCCNC(C)(C)C)C=1CC1=CC=2OCOC=2C=C1C=1C=CNN=1 MCINGXDOYPFFSW-UHFFFAOYSA-N 0.000 claims 1
- ONIPFSPBFSJZEJ-UHFFFAOYSA-N 9-[3-(tert-butylamino)propyl]-2-fluoro-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound O1C(C)=CC=C1C(C(=C1)CC=2N(C3=NC(F)=NC(N)=C3N=2)CCCNC(C)(C)C)=CC2=C1OCO2 ONIPFSPBFSJZEJ-UHFFFAOYSA-N 0.000 claims 1
- OOFNHTRLWRORBW-UHFFFAOYSA-N 9-[3-(tert-butylamino)propyl]-8-[(6-ethynyl-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCCNC(C)(C)C)C(SC=3C(=CC=4OCOC=4C=3)C#C)=NC2=C1N OOFNHTRLWRORBW-UHFFFAOYSA-N 0.000 claims 1
- IPKZNVCTXDGKNO-UHFFFAOYSA-N 9-[3-(tert-butylamino)propyl]-8-[[6-(1h-pyrazol-5-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)(C)C)C=1SC1=CC=2OCOC=2C=C1C=1C=CNN=1 IPKZNVCTXDGKNO-UHFFFAOYSA-N 0.000 claims 1
- LIXWOZSNJHTHPI-UHFFFAOYSA-N 9-[3-(tert-butylamino)propyl]-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound O1C(C)=CC=C1C(C(=C1)SC=2N(C3=NC=NC(N)=C3N=2)CCCNC(C)(C)C)=CC2=C1OCO2 LIXWOZSNJHTHPI-UHFFFAOYSA-N 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 claims 1
- 125000003431 oxalo group Chemical group 0.000 claims 1
- ICFQGMYPBURXAZ-UHFFFAOYSA-N pentane-1-sulfonamide Chemical compound CCCCCS(N)(=O)=O ICFQGMYPBURXAZ-UHFFFAOYSA-N 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 346
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 286
- 238000005481 NMR spectroscopy Methods 0.000 description 183
- 239000011541 reaction mixture Substances 0.000 description 182
- 229910052757 nitrogen Inorganic materials 0.000 description 177
- 238000000034 method Methods 0.000 description 126
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 126
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- 239000000460 chlorine Substances 0.000 description 108
- 230000002829 reductive effect Effects 0.000 description 97
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 93
- 239000002904 solvent Substances 0.000 description 75
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 74
- 238000012746 preparative thin layer chromatography Methods 0.000 description 74
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 70
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 58
- 239000000243 solution Substances 0.000 description 58
- 238000004128 high performance liquid chromatography Methods 0.000 description 57
- 239000007787 solid Substances 0.000 description 57
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 54
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 50
- 235000019439 ethyl acetate Nutrition 0.000 description 44
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 42
- SUPVGFZUWFMATN-UHFFFAOYSA-N zelavespib Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC=4OCOC=4C=3)I)=NC2=C1N SUPVGFZUWFMATN-UHFFFAOYSA-N 0.000 description 33
- 238000003818 flash chromatography Methods 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 25
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 23
- 239000003153 chemical reaction reagent Substances 0.000 description 22
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 22
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 20
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- 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 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 17
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 17
- 125000001424 substituent group Chemical group 0.000 description 17
- BHVOFCPOXNYVCE-UHFFFAOYSA-N 6-amino-7,9-dihydropurine-8-thione Chemical compound NC1=NC=NC2=C1NC(=S)N2 BHVOFCPOXNYVCE-UHFFFAOYSA-N 0.000 description 16
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 16
- 238000010992 reflux Methods 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 14
- 239000013592 cell lysate Substances 0.000 description 14
- 238000004587 chromatography analysis Methods 0.000 description 14
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 14
- 229910002666 PdCl2 Inorganic materials 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 210000004958 brain cell Anatomy 0.000 description 12
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- 229960000643 adenine Drugs 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 description 11
- 235000010288 sodium nitrite Nutrition 0.000 description 11
- 238000003786 synthesis reaction Methods 0.000 description 11
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- 125000000623 heterocyclic group Chemical group 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- HVLLSGMXQDNUAL-UHFFFAOYSA-N triphenyl phosphite Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)OC1=CC=CC=C1 HVLLSGMXQDNUAL-UHFFFAOYSA-N 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Substances [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
- 125000003277 amino group Chemical group 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- XDIAMRVROCPPBK-UHFFFAOYSA-N 2,2-dimethylpropan-1-amine Chemical compound CC(C)(C)CN XDIAMRVROCPPBK-UHFFFAOYSA-N 0.000 description 7
- UYODNJZBUUEXPC-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCNCC(C)(C)C)C(SC=3C(=CC=4OCOC=4C=3)I)=NC2=C1N UYODNJZBUUEXPC-UHFFFAOYSA-N 0.000 description 7
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical class NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 229910000024 caesium carbonate Inorganic materials 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- PZJSZBJLOWMDRG-UHFFFAOYSA-N furan-2-ylboronic acid Chemical compound OB(O)C1=CC=CO1 PZJSZBJLOWMDRG-UHFFFAOYSA-N 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- NEUWPDLMDVINSN-UHFFFAOYSA-N 1h-pyrazol-5-ylboronic acid Chemical compound OB(O)C=1C=CNN=1 NEUWPDLMDVINSN-UHFFFAOYSA-N 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- 101710113864 Heat shock protein 90 Proteins 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 150000002430 hydrocarbons Chemical class 0.000 description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 229910052717 sulfur Inorganic materials 0.000 description 6
- 101710178035 Chorismate synthase 2 Proteins 0.000 description 5
- 101710152694 Cysteine synthase 2 Proteins 0.000 description 5
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 108010006519 Molecular Chaperones Proteins 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 229940088710 antibiotic agent Drugs 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 5
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 4
- 229930024421 Adenine Chemical class 0.000 description 4
- UEXCJVNBTNXOEH-UHFFFAOYSA-N Ethynylbenzene Chemical group C#CC1=CC=CC=C1 UEXCJVNBTNXOEH-UHFFFAOYSA-N 0.000 description 4
- 229910003556 H2 SO4 Inorganic materials 0.000 description 4
- 102000005431 Molecular Chaperones Human genes 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 239000012230 colorless oil Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 4
- 150000003222 pyridines Chemical class 0.000 description 4
- PZRKPUQWIFJRKZ-UHFFFAOYSA-N pyrimidine-2,4,5,6-tetramine Chemical compound NC1=NC(N)=C(N)C(N)=N1 PZRKPUQWIFJRKZ-UHFFFAOYSA-N 0.000 description 4
- ATEBXHFBFRCZMA-VXTBVIBXSA-N rifabutin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC(=C2N3)C(=O)C=4C(O)=C5C)C)OC)C5=C1C=4C2=NC13CCN(CC(C)C)CC1 ATEBXHFBFRCZMA-VXTBVIBXSA-N 0.000 description 4
- 229960000885 rifabutin Drugs 0.000 description 4
- ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 4
- YOWGRWHKDCHINP-UHFFFAOYSA-N tributyl(1,3-oxazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CO1 YOWGRWHKDCHINP-UHFFFAOYSA-N 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- HANPIZQMFCWPKY-UHFFFAOYSA-N 1,2-oxazol-4-ylboronic acid Chemical compound OB(O)C=1C=NOC=1 HANPIZQMFCWPKY-UHFFFAOYSA-N 0.000 description 3
- FNPZFZKLYGWKLH-UHFFFAOYSA-N 4,4,5,5-tetramethyl-2-(5-methylfuran-2-yl)-1,3,2-dioxaborolane Chemical compound O1C(C)=CC=C1B1OC(C)(C)C(C)(C)O1 FNPZFZKLYGWKLH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 3
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- 238000006069 Suzuki reaction reaction Methods 0.000 description 3
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 3
- 125000000278 alkyl amino alkyl group Chemical group 0.000 description 3
- 150000001412 amines Chemical group 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 230000008499 blood brain barrier function Effects 0.000 description 3
- 210000001218 blood-brain barrier Anatomy 0.000 description 3
- 238000006880 cross-coupling reaction Methods 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 125000001153 fluoro group Chemical group F* 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000004153 renaturation Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 3
- MGNBKNBEZGLHNF-UHFFFAOYSA-N (2-methylpyrazol-3-yl)boronic acid Chemical compound CN1N=CC=C1B(O)O MGNBKNBEZGLHNF-UHFFFAOYSA-N 0.000 description 2
- JUWYQISLQJRRNT-UHFFFAOYSA-N (5-formylfuran-2-yl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)O1 JUWYQISLQJRRNT-UHFFFAOYSA-N 0.000 description 2
- ARGCQEVBJHPOGB-UHFFFAOYSA-N 2,5-dihydrofuran Chemical compound C1OCC=C1 ARGCQEVBJHPOGB-UHFFFAOYSA-N 0.000 description 2
- SFVHZPMQGRFPMM-UHFFFAOYSA-N 2-(1-benzofuran-6-yl)acetic acid Chemical compound OC(=O)CC1=CC=C2C=COC2=C1 SFVHZPMQGRFPMM-UHFFFAOYSA-N 0.000 description 2
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 description 2
- OQLYCXDIPBIKAX-UHFFFAOYSA-N 2-fluoro-8-[[6-(furan-2-yl)-1,3-benzodioxol-5-yl]methyl]-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=CC=CO1 OQLYCXDIPBIKAX-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 108010058765 Oncogene Protein pp60(v-src) Proteins 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
- 235000007235 Spartium junceum Nutrition 0.000 description 2
- 240000005622 Spartium junceum Species 0.000 description 2
- 108010085012 Steroid Receptors Proteins 0.000 description 2
- ZWGMJLNXIVRFRJ-UHFFFAOYSA-N [1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrol-2-yl]boronic acid Chemical compound CC(C)(C)OC(=O)N1C=CC=C1B(O)O ZWGMJLNXIVRFRJ-UHFFFAOYSA-N 0.000 description 2
- JTFQDOHHXGSMFC-UHFFFAOYSA-N [1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrol-3-yl]boronic acid Chemical compound CC(C)(C)OC(=O)N1C=CC(B(O)O)=C1 JTFQDOHHXGSMFC-UHFFFAOYSA-N 0.000 description 2
- AHWZCYVXODSVGD-UHFFFAOYSA-N [2,3-bis(trifluoromethyl)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(C(F)(F)F)=C1C(F)(F)F AHWZCYVXODSVGD-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000001588 bifunctional effect Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- CYEFKCRAAGLNHW-UHFFFAOYSA-N furan-3-ylboronic acid Chemical compound OB(O)C=1C=COC=1 CYEFKCRAAGLNHW-UHFFFAOYSA-N 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000019491 signal transduction Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 102000005969 steroid hormone receptors Human genes 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 2
- QBLFZIBJXUQVRF-UHFFFAOYSA-N (4-bromophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C=C1 QBLFZIBJXUQVRF-UHFFFAOYSA-N 0.000 description 1
- VXWBQOJISHAKKM-UHFFFAOYSA-N (4-formylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=O)C=C1 VXWBQOJISHAKKM-UHFFFAOYSA-N 0.000 description 1
- VOAAEKKFGLPLLU-UHFFFAOYSA-N (4-methoxyphenyl)boronic acid Chemical compound COC1=CC=C(B(O)O)C=C1 VOAAEKKFGLPLLU-UHFFFAOYSA-N 0.000 description 1
- MNJYZNVROSZZQC-UHFFFAOYSA-N (4-tert-butylphenyl)boronic acid Chemical compound CC(C)(C)C1=CC=C(B(O)O)C=C1 MNJYZNVROSZZQC-UHFFFAOYSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 1
- VRPLZTMSEURZKM-UHFFFAOYSA-N 1,1-dibromoethanol Chemical compound CC(O)(Br)Br VRPLZTMSEURZKM-UHFFFAOYSA-N 0.000 description 1
- JNVXRQOSRUDXDY-UHFFFAOYSA-N 1,1-diiodoethane Chemical compound CC(I)I JNVXRQOSRUDXDY-UHFFFAOYSA-N 0.000 description 1
- HGVWMTAIIYNQSI-UHFFFAOYSA-N 1-(2,3-dihydro-1,4-benzodioxin-6-yl)ethanone Chemical compound O1CCOC2=CC(C(=O)C)=CC=C21 HGVWMTAIIYNQSI-UHFFFAOYSA-N 0.000 description 1
- BZKOZYWGZKRTIB-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-amine Chemical compound O1CCOC2=CC(N)=CC=C21 BZKOZYWGZKRTIB-UHFFFAOYSA-N 0.000 description 1
- ZDLCRJZSWKJVQO-UHFFFAOYSA-N 2,3-dihydro-1-benzofuran-6-amine Chemical compound NC1=CC=C2CCOC2=C1 ZDLCRJZSWKJVQO-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
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
- BVRNERFWPQRVJB-UHFFFAOYSA-N 2-(2,3-dihydro-1,4-benzodioxin-6-yl)acetic acid Chemical compound O1CCOC2=CC(CC(=O)O)=CC=C21 BVRNERFWPQRVJB-UHFFFAOYSA-N 0.000 description 1
- VLZVIIYRNMWPSN-UHFFFAOYSA-N 2-Amino-4-nitrophenol Chemical compound NC1=CC([N+]([O-])=O)=CC=C1O VLZVIIYRNMWPSN-UHFFFAOYSA-N 0.000 description 1
- ZBJGWPVYKPHHDQ-UHFFFAOYSA-N 2-[6-[6-amino-9-[3-(propan-2-ylamino)propyl]purin-8-yl]sulfanyl-1,3-benzodioxol-5-yl]acetonitrile Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC=4OCOC=4C=3)CC#N)=NC2=C1N ZBJGWPVYKPHHDQ-UHFFFAOYSA-N 0.000 description 1
- ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 1
- PGYJSURPYAAOMM-UHFFFAOYSA-N 2-ethenoxy-2-methylpropane Chemical group CC(C)(C)OC=C PGYJSURPYAAOMM-UHFFFAOYSA-N 0.000 description 1
- NDJSGZXZPFMUSO-UHFFFAOYSA-N 2-fluoro-8-[(5-iodo-2,3-dihydro-1-benzofuran-6-yl)methyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N1=C(F)N=C2N(CCCNC(C)C)C(CC=3C(=CC=4CCOC=4C=3)I)=NC2=C1N NDJSGZXZPFMUSO-UHFFFAOYSA-N 0.000 description 1
- HEOKCSNULQGUDC-UHFFFAOYSA-N 2-fluoro-8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]-7h-purin-6-amine Chemical compound O1CCOC(C=C2I)=C1C=C2CC(N1)=NC2=C1N=C(F)N=C2N HEOKCSNULQGUDC-UHFFFAOYSA-N 0.000 description 1
- TXMLZUQWTYJIEN-UHFFFAOYSA-N 2-fluoro-8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N1=C(F)N=C2N(CCNCC(C)C)C(CC=3C(=CC=4OCCOC=4C=3)I)=NC2=C1N TXMLZUQWTYJIEN-UHFFFAOYSA-N 0.000 description 1
- KOMHXZUPKHZEBA-UHFFFAOYSA-N 2-fluoro-8-[[6-(furan-2-yl)-2,3-dihydro-1,4-benzodioxin-7-yl]methyl]-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCCOC=2C=C1C1=CC=CO1 KOMHXZUPKHZEBA-UHFFFAOYSA-N 0.000 description 1
- WOUXACOFQYCEPE-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(1,2-oxazol-4-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C=1C=NOC=1 WOUXACOFQYCEPE-UHFFFAOYSA-N 0.000 description 1
- CQPLXGHIFFQSIY-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(1h-pyrazol-4-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C=1C=NNC=1 CQPLXGHIFFQSIY-UHFFFAOYSA-N 0.000 description 1
- YKYKGUZCRVLEFP-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(1h-pyrrol-2-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=CC=CN1 YKYKGUZCRVLEFP-UHFFFAOYSA-N 0.000 description 1
- PIDGEDVDPJRILE-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(1h-pyrrol-3-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C=1C=CNC=1 PIDGEDVDPJRILE-UHFFFAOYSA-N 0.000 description 1
- RBNQXWJEBMDLEP-UHFFFAOYSA-N 2-fluoro-9-[2-(2-methylpropylamino)ethyl]-8-[[6-(2-methylpyrazol-3-yl)-1,3-benzodioxol-5-yl]methyl]purin-6-amine Chemical compound N=1C2=C(N)N=C(F)N=C2N(CCNCC(C)C)C=1CC1=CC=2OCOC=2C=C1C1=CC=NN1C RBNQXWJEBMDLEP-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- UOBYKYZJUGYBDK-UHFFFAOYSA-N 2-naphthoic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CC=C21 UOBYKYZJUGYBDK-UHFFFAOYSA-N 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- PPWNCLVNXGCGAF-UHFFFAOYSA-N 3,3-dimethylbut-1-yne Chemical group CC(C)(C)C#C PPWNCLVNXGCGAF-UHFFFAOYSA-N 0.000 description 1
- XSSUVEGETJVOSH-UHFFFAOYSA-N 3,5-dihydropurin-6-one Chemical group O=C1N=CNC2=NC=NC12 XSSUVEGETJVOSH-UHFFFAOYSA-N 0.000 description 1
- FVMDYYGIDFPZAX-UHFFFAOYSA-N 3-hydroxyphenylacetic acid Chemical compound OC(=O)CC1=CC=CC(O)=C1 FVMDYYGIDFPZAX-UHFFFAOYSA-N 0.000 description 1
- KAOTXIGLMDOHJJ-UHFFFAOYSA-N 3-iodonaphthalen-2-amine Chemical compound C1=CC=C2C=C(I)C(N)=CC2=C1 KAOTXIGLMDOHJJ-UHFFFAOYSA-N 0.000 description 1
- 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- WSNGLKSRNDDZHQ-UHFFFAOYSA-N 4-[6-[6-amino-9-[3-(propan-2-ylamino)propyl]purin-8-yl]sulfanyl-1,3-benzodioxol-5-yl]benzaldehyde Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=C(C=O)C=C1 WSNGLKSRNDDZHQ-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- ZTBQQMRMUWBAOB-UHFFFAOYSA-N 4-methyl-2,3-dihydro-1,4-benzoxazin-6-amine Chemical compound C1=C(N)C=C2N(C)CCOC2=C1 ZTBQQMRMUWBAOB-UHFFFAOYSA-N 0.000 description 1
- FJSDSFYITDCJDA-UHFFFAOYSA-N 4-methyl-6-nitro-2,3-dihydro-1,4-benzoxazine Chemical compound C1=C([N+]([O-])=O)C=C2N(C)CCOC2=C1 FJSDSFYITDCJDA-UHFFFAOYSA-N 0.000 description 1
- DUNWZGVRJJWWRZ-UHFFFAOYSA-N 5-[6-[6-amino-9-[3-(propan-2-ylamino)propyl]purin-8-yl]sulfanyl-1,3-benzodioxol-5-yl]furan-2-carbaldehyde Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=C(C=O)O1 DUNWZGVRJJWWRZ-UHFFFAOYSA-N 0.000 description 1
- YQGADULPCIXSJV-UHFFFAOYSA-N 5-iodo-2,3-dihydro-1-benzofuran-6-amine Chemical compound C1=C(I)C(N)=CC2=C1CCO2 YQGADULPCIXSJV-UHFFFAOYSA-N 0.000 description 1
- KWXSEMPJXZFOSP-UHFFFAOYSA-N 5-iodo-6-nitro-2,3-dihydro-1h-indene Chemical compound C1=C(I)C([N+](=O)[O-])=CC2=C1CCC2 KWXSEMPJXZFOSP-UHFFFAOYSA-N 0.000 description 1
- HZTMYTXWFHBHDC-UHFFFAOYSA-N 6-iodo-2,3-dihydro-1,4-benzodioxine Chemical compound O1CCOC2=CC(I)=CC=C21 HZTMYTXWFHBHDC-UHFFFAOYSA-N 0.000 description 1
- WYSWTNFLUWTOLA-UHFFFAOYSA-N 6-iodo-2,3-dihydro-1-benzofuran Chemical compound IC1=CC=C2CCOC2=C1 WYSWTNFLUWTOLA-UHFFFAOYSA-N 0.000 description 1
- UPHIJLSUBXGZDN-UHFFFAOYSA-N 6-iodo-2,3-dihydro-1h-inden-5-amine Chemical compound C1=C(I)C(N)=CC2=C1CCC2 UPHIJLSUBXGZDN-UHFFFAOYSA-N 0.000 description 1
- WFHLBXBWGXRUFO-UHFFFAOYSA-N 6-iodo-4-methyl-2,3-dihydro-1,4-benzoxazine Chemical compound C1=C(I)C=C2N(C)CCOC2=C1 WFHLBXBWGXRUFO-UHFFFAOYSA-N 0.000 description 1
- HLUYEDQKIFUIIP-UHFFFAOYSA-N 6-nitro-2,3-dihydro-1h-inden-5-amine Chemical compound C1=C([N+]([O-])=O)C(N)=CC2=C1CCC2 HLUYEDQKIFUIIP-UHFFFAOYSA-N 0.000 description 1
- GZAJZBARYACGSO-UHFFFAOYSA-N 6-nitro-3,4-dihydro-2h-1,4-benzoxazine Chemical compound O1CCNC2=CC([N+](=O)[O-])=CC=C21 GZAJZBARYACGSO-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- BSOSYDPCRDZIPG-UHFFFAOYSA-N 8-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-2-fluoro-7h-purin-6-amine Chemical compound O1CCOC2=CC(CC=3NC=4N=C(F)N=C(C=4N=3)N)=CC=C21 BSOSYDPCRDZIPG-UHFFFAOYSA-N 0.000 description 1
- MYIXDYQABWOTGD-UHFFFAOYSA-N 8-(2,3-dihydro-1,4-benzodioxin-6-ylmethyl)-7h-purine-2,6-diamine Chemical compound O1CCOC2=CC(CC3=NC4=C(N)N=C(N=C4N3)N)=CC=C21 MYIXDYQABWOTGD-UHFFFAOYSA-N 0.000 description 1
- IJGNXHMGSHWYMI-UHFFFAOYSA-N 8-(2,3-dihydro-1-benzofuran-6-ylmethyl)-2-fluoro-7h-purin-6-amine Chemical compound C1=C2CCOC2=CC(CC=2NC=3N=C(F)N=C(C=3N=2)N)=C1 IJGNXHMGSHWYMI-UHFFFAOYSA-N 0.000 description 1
- DSPTXZGHDKLHKT-UHFFFAOYSA-N 8-(2,3-dihydro-1-benzofuran-6-ylmethyl)-7h-purine-2,6-diamine Chemical compound C1=C2CCOC2=CC(CC2=NC3=C(N)N=C(N=C3N2)N)=C1 DSPTXZGHDKLHKT-UHFFFAOYSA-N 0.000 description 1
- JJMVOSZFKUVWDI-UHFFFAOYSA-N 8-(3-aminonaphthalen-2-yl)sulfanyl-7h-purin-6-amine Chemical compound N1=CN=C2NC(SC3=CC4=CC=CC=C4C=C3N)=NC2=C1N JJMVOSZFKUVWDI-UHFFFAOYSA-N 0.000 description 1
- SQLMTMCDBGCHEF-UHFFFAOYSA-N 8-(3-iodonaphthalen-2-yl)sulfanyl-7h-purin-6-amine Chemical compound C1=CC=C2C=C(I)C(SC=3NC=4N=CN=C(C=4N=3)N)=CC2=C1 SQLMTMCDBGCHEF-UHFFFAOYSA-N 0.000 description 1
- RWDCITLWLGCCJT-UHFFFAOYSA-N 8-(3-iodonaphthalen-2-yl)sulfanyl-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC4=CC=CC=C4C=3)I)=NC2=C1N RWDCITLWLGCCJT-UHFFFAOYSA-N 0.000 description 1
- MBLGEUGNABDCDM-UHFFFAOYSA-N 8-[(5-iodo-2,3-dihydro-1-benzofuran-6-yl)sulfanyl]-7h-purin-6-amine Chemical compound N=1C=2C(N)=NC=NC=2NC=1SC(C(=C1)I)=CC2=C1CCO2 MBLGEUGNABDCDM-UHFFFAOYSA-N 0.000 description 1
- QTCOVPRGVVTMJX-UHFFFAOYSA-N 8-[(5-iodo-2,3-dihydro-1-benzofuran-6-yl)sulfanyl]-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N1=CN=C2N(CCNCC(C)C)C(SC=3C(=CC=4CCOC=4C=3)I)=NC2=C1N QTCOVPRGVVTMJX-UHFFFAOYSA-N 0.000 description 1
- MZWFMXHWZJGGMO-UHFFFAOYSA-N 8-[(5-iodo-2,3-dihydro-1-benzofuran-6-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC=4CCOC=4C=3)I)=NC2=C1N MZWFMXHWZJGGMO-UHFFFAOYSA-N 0.000 description 1
- XPFTXWUUMGLYEB-UHFFFAOYSA-N 8-[(6-amino-2,3-dihydro-1-benzofuran-5-yl)sulfanyl]-7h-purin-6-amine Chemical compound N1=CN=C2NC(SC3=CC=4CCOC=4C=C3N)=NC2=C1N XPFTXWUUMGLYEB-UHFFFAOYSA-N 0.000 description 1
- ZCUIMZDWVHHYOX-UHFFFAOYSA-N 8-[(6-amino-2,3-dihydro-1h-inden-5-yl)sulfanyl]-7h-purin-6-amine Chemical compound C1=NC(N)=C2NC(SC3=CC=4CCCC=4C=C3N)=NC2=N1 ZCUIMZDWVHHYOX-UHFFFAOYSA-N 0.000 description 1
- CCUJDAFDSKDDEF-UHFFFAOYSA-N 8-[(6-cyclopent-2-en-1-yl-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1CCC=C1 CCUJDAFDSKDDEF-UHFFFAOYSA-N 0.000 description 1
- WQSGPJCMKZBDNJ-UHFFFAOYSA-N 8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)sulfanyl]-7h-purin-6-amine Chemical compound O1CCOC(C=C2I)=C1C=C2SC(N1)=NC2=C1N=CN=C2N WQSGPJCMKZBDNJ-UHFFFAOYSA-N 0.000 description 1
- OGVPPEHQZFHZET-UHFFFAOYSA-N 8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC=4OCCOC=4C=3)I)=NC2=C1N OGVPPEHQZFHZET-UHFFFAOYSA-N 0.000 description 1
- AGPIGMGCFKFFFQ-UHFFFAOYSA-N 8-[(6-iodo-2,3-dihydro-1-benzofuran-5-yl)sulfanyl]-7h-purin-6-amine Chemical compound N=1C=2C(N)=NC=NC=2NC=1SC(C(=C1)I)=CC2=C1OCC2 AGPIGMGCFKFFFQ-UHFFFAOYSA-N 0.000 description 1
- NUZQGTULLXBAPU-UHFFFAOYSA-N 8-[(6-iodo-2,3-dihydro-1h-inden-5-yl)sulfanyl]-7h-purin-6-amine Chemical compound N=1C=2C(N)=NC=NC=2NC=1SC(C(=C1)I)=CC2=C1CCC2 NUZQGTULLXBAPU-UHFFFAOYSA-N 0.000 description 1
- RELHYURXNSIYSF-UHFFFAOYSA-N 8-[(6-phenyl-1,3-benzodioxol-5-yl)sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=CC=C1 RELHYURXNSIYSF-UHFFFAOYSA-N 0.000 description 1
- ZNBXSZDJFOEVQV-UHFFFAOYSA-N 8-[[6-(2,3-dihydrofuran-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1CC=CO1 ZNBXSZDJFOEVQV-UHFFFAOYSA-N 0.000 description 1
- SBBDCFJBVJRRTR-UHFFFAOYSA-N 8-[[6-(2,3-dihydrofuran-3-yl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1COC=C1 SBBDCFJBVJRRTR-UHFFFAOYSA-N 0.000 description 1
- IAOHWVYJJOUESG-UHFFFAOYSA-N 8-[[6-(2,5-dihydro-1h-pyrrol-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1NCC=C1 IAOHWVYJJOUESG-UHFFFAOYSA-N 0.000 description 1
- UMNPWMNQKYHYAY-UHFFFAOYSA-N 8-[[6-(2-methylpyrazol-3-yl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=NN1C UMNPWMNQKYHYAY-UHFFFAOYSA-N 0.000 description 1
- AKBACXFLRRJLFR-UHFFFAOYSA-N 8-[[6-(3,3-dimethylbut-1-ynyl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N1=CN=C2N(CCCNC(C)C)C(SC=3C(=CC=4OCOC=4C=3)C#CC(C)(C)C)=NC2=C1N AKBACXFLRRJLFR-UHFFFAOYSA-N 0.000 description 1
- FLFOFGBWJKBAJL-UHFFFAOYSA-N 8-[[6-(furan-3-yl)-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C=1C=COC=1 FLFOFGBWJKBAJL-UHFFFAOYSA-N 0.000 description 1
- HQZYTXXPDZOQDF-UHFFFAOYSA-N 8-[[6-[4-(dimethylamino)phenyl]-1,3-benzodioxol-5-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=C(N(C)C)C=C1 HQZYTXXPDZOQDF-UHFFFAOYSA-N 0.000 description 1
- MUGGGVXWICQHOU-UHFFFAOYSA-N 8-[[7-(1,3-oxazol-2-yl)-2,3-dihydro-1,4-benzodioxin-6-yl]sulfanyl]-9-[3-(propan-2-ylamino)propyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCCOC=2C=C1C1=NC=CO1 MUGGGVXWICQHOU-UHFFFAOYSA-N 0.000 description 1
- NNRROXQPVRFSEK-UHFFFAOYSA-N 8-[[7-(furan-2-yl)-2,3-dihydro-1,4-benzodioxin-6-yl]sulfanyl]-9-[2-(2-methylpropylamino)ethyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)C)C=1SC1=CC=2OCCOC=2C=C1C1=CC=CO1 NNRROXQPVRFSEK-UHFFFAOYSA-N 0.000 description 1
- SERDKQSFCYHJER-UHFFFAOYSA-N 9-(2-bromoethyl)-2-fluoro-8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]purin-6-amine Chemical compound O1CCOC(C=C2I)=C1C=C2CC(N1CCBr)=NC2=C1N=C(F)N=C2N SERDKQSFCYHJER-UHFFFAOYSA-N 0.000 description 1
- HQDYUQMYJMUVOC-UHFFFAOYSA-N 9-(2-bromoethyl)-8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)sulfanyl]purin-6-amine Chemical compound O1CCOC(C=C2I)=C1C=C2SC(N1CCBr)=NC2=C1N=CN=C2N HQDYUQMYJMUVOC-UHFFFAOYSA-N 0.000 description 1
- WBJHBCYKTBUULP-UHFFFAOYSA-N 9-(2-bromoethyl)-8-[(6-iodo-2,3-dihydro-1h-inden-5-yl)sulfanyl]purin-6-amine Chemical compound N=1C=2C(N)=NC=NC=2N(CCBr)C=1SC(C(=C1)I)=CC2=C1CCC2 WBJHBCYKTBUULP-UHFFFAOYSA-N 0.000 description 1
- FTGHFXMKOIQFOU-UHFFFAOYSA-N 9-(3-bromopropyl)-2-fluoro-8-[(5-iodo-2,3-dihydro-1-benzofuran-6-yl)methyl]purin-6-amine Chemical compound N=1C=2C(N)=NC(F)=NC=2N(CCCBr)C=1CC(C(=C1)I)=CC2=C1CCO2 FTGHFXMKOIQFOU-UHFFFAOYSA-N 0.000 description 1
- SYNIUTMQOGFIOZ-UHFFFAOYSA-N 9-(3-bromopropyl)-8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)sulfanyl]purin-6-amine Chemical compound O1CCOC(C=C2I)=C1C=C2SC(N1CCCBr)=NC2=C1N=CN=C2N SYNIUTMQOGFIOZ-UHFFFAOYSA-N 0.000 description 1
- RMIANEPUQOPXQF-UHFFFAOYSA-N 9-(3-bromopropyl)-8-[(6-iodo-2,3-dihydro-1-benzofuran-5-yl)sulfanyl]purin-6-amine Chemical compound N=1C=2C(N)=NC=NC=2N(CCCBr)C=1SC(C(=C1)I)=CC2=C1OCC2 RMIANEPUQOPXQF-UHFFFAOYSA-N 0.000 description 1
- PNZGTLGQBZEGDO-UHFFFAOYSA-N 9-(3-imidazol-1-ylpropyl)-8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)sulfanyl]purin-6-amine Chemical compound C=1C=2OCCOC=2C=C(I)C=1SC1=NC=2C(N)=NC=NC=2N1CCCN1C=CN=C1 PNZGTLGQBZEGDO-UHFFFAOYSA-N 0.000 description 1
- DIBMXFJVQGNKAJ-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-2-fluoro-8-[(5-iodo-2,3-dihydro-1-benzofuran-6-yl)methyl]purin-6-amine Chemical compound N1=C(F)N=C2N(CCNCC(C)(C)C)C(CC=3C(=CC=4CCOC=4C=3)I)=NC2=C1N DIBMXFJVQGNKAJ-UHFFFAOYSA-N 0.000 description 1
- NJNKSCQLKJFJDP-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-(2-ethynyl-5-methoxyphenyl)sulfanylpurin-6-amine Chemical compound COC1=CC=C(C#C)C(SC=2N(C3=NC=NC(N)=C3N=2)CCNCC(C)(C)C)=C1 NJNKSCQLKJFJDP-UHFFFAOYSA-N 0.000 description 1
- QGWBWRZAEAMZCO-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-(5-methoxy-2-thiophen-2-ylphenyl)sulfanylpurin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)(C)C)C=1SC1=CC(OC)=CC=C1C1=CC=CS1 QGWBWRZAEAMZCO-UHFFFAOYSA-N 0.000 description 1
- YVMQDVQLTUCVFQ-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(5-iodo-2,3-dihydro-1-benzofuran-6-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCNCC(C)(C)C)C(SC=3C(=CC=4CCOC=4C=3)I)=NC2=C1N YVMQDVQLTUCVFQ-UHFFFAOYSA-N 0.000 description 1
- JCHVHNXVRNVJSL-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(5-thiophen-2-yl-2,3-dihydro-1-benzofuran-6-yl)sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)(C)C)C=1SC1=CC=2OCCC=2C=C1C1=CC=CS1 JCHVHNXVRNVJSL-UHFFFAOYSA-N 0.000 description 1
- ZFMJTBHCAGPOJA-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(6-ethynyl-2,3-dihydro-1h-inden-5-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCNCC(C)(C)C)C(SC=3C(=CC=4CCCC=4C=3)C#C)=NC2=C1N ZFMJTBHCAGPOJA-UHFFFAOYSA-N 0.000 description 1
- HIHAAXIARJFGSG-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(6-iodo-2,3-dihydro-1h-inden-5-yl)sulfanyl]purin-6-amine Chemical compound N1=CN=C2N(CCNCC(C)(C)C)C(SC=3C(=CC=4CCCC=4C=3)I)=NC2=C1N HIHAAXIARJFGSG-UHFFFAOYSA-N 0.000 description 1
- CDOZXEGDSNFSHT-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[(6-thiophen-2-yl-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=CS1 CDOZXEGDSNFSHT-UHFFFAOYSA-N 0.000 description 1
- VSLGCTHNSARJOW-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[[5-(furan-2-yl)-2,3-dihydro-1-benzofuran-6-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)(C)C)C=1SC1=CC=2OCCC=2C=C1C1=CC=CO1 VSLGCTHNSARJOW-UHFFFAOYSA-N 0.000 description 1
- XYKBWZPRALXFAF-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[[6-(1h-pyrazol-5-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)(C)C)C=1SC1=CC=2OCOC=2C=C1C=1C=CNN=1 XYKBWZPRALXFAF-UHFFFAOYSA-N 0.000 description 1
- UFRAEMHCSYZROE-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[[6-(1h-pyrrol-3-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)(C)C)C=1SC1=CC=2OCOC=2C=C1C=1C=CNC=1 UFRAEMHCSYZROE-UHFFFAOYSA-N 0.000 description 1
- ARGYBNGENDCNMI-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[[6-(5-methylfuran-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound O1C(C)=CC=C1C(C(=C1)SC=2N(C3=NC=NC(N)=C3N=2)CCNCC(C)(C)C)=CC2=C1OCO2 ARGYBNGENDCNMI-UHFFFAOYSA-N 0.000 description 1
- DQNHWUSZIPYTTI-UHFFFAOYSA-N 9-[2-(2,2-dimethylpropylamino)ethyl]-8-[[6-(furan-3-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCNCC(C)(C)C)C=1SC1=CC=2OCOC=2C=C1C=1C=COC=1 DQNHWUSZIPYTTI-UHFFFAOYSA-N 0.000 description 1
- LKMXLYQQZJUOCO-UHFFFAOYSA-N 9-[2-(tert-butylamino)ethyl]-2-fluoro-8-[(6-iodo-2,3-dihydro-1,4-benzodioxin-7-yl)methyl]purin-6-amine Chemical compound N1=C(F)N=C2N(CCNC(C)(C)C)C(CC=3C(=CC=4OCCOC=4C=3)I)=NC2=C1N LKMXLYQQZJUOCO-UHFFFAOYSA-N 0.000 description 1
- XSBNXASDFOVWDO-UHFFFAOYSA-N 9-[3-(propan-2-ylamino)propyl]-8-[(6-pyridin-4-yl-1,3-benzodioxol-5-yl)sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=NC=C1 XSBNXASDFOVWDO-UHFFFAOYSA-N 0.000 description 1
- XUPXJJHPZYKNGS-UHFFFAOYSA-N 9-[3-(propan-2-ylamino)propyl]-8-[[6-(1h-pyrazol-4-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C=1C=NNC=1 XUPXJJHPZYKNGS-UHFFFAOYSA-N 0.000 description 1
- BRXWSOPKSFKQNF-UHFFFAOYSA-N 9-[3-(propan-2-ylamino)propyl]-8-[[6-(1h-pyrrol-2-yl)-1,3-benzodioxol-5-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCOC=2C=C1C1=CC=CN1 BRXWSOPKSFKQNF-UHFFFAOYSA-N 0.000 description 1
- QYQXGIZZYBHEKJ-UHFFFAOYSA-N 9-[3-(propan-2-ylamino)propyl]-8-[[7-(1h-pyrazol-5-yl)-2,3-dihydro-1,4-benzodioxin-6-yl]sulfanyl]purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCNC(C)C)C=1SC1=CC=2OCCOC=2C=C1C=1C=CNN=1 QYQXGIZZYBHEKJ-UHFFFAOYSA-N 0.000 description 1
- 108091006112 ATPases Proteins 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000057290 Adenosine Triphosphatases Human genes 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 101100327692 Caenorhabditis elegans hsp-60 gene Proteins 0.000 description 1
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 description 1
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 1
- 101150065069 Hsp90b1 gene Proteins 0.000 description 1
- 206010021143 Hypoxia Diseases 0.000 description 1
- 102000000521 Immunophilins Human genes 0.000 description 1
- 108010016648 Immunophilins Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 229910004809 Na2 SO4 Inorganic materials 0.000 description 1
- 239000007832 Na2SO4 Substances 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229920000305 Nylon 6,10 Polymers 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 101150003085 Pdcl gene Proteins 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- IUEPVMMFUSDDBJ-UHFFFAOYSA-N [1-[(2-methylpropan-2-yl)oxycarbonyl]pyrazol-4-yl]boronic acid Chemical compound CC(C)(C)OC(=O)N1C=C(B(O)O)C=N1 IUEPVMMFUSDDBJ-UHFFFAOYSA-N 0.000 description 1
- RIIPFHVHLXPMHQ-UHFFFAOYSA-N [4-(dimethylamino)phenyl]boronic acid Chemical compound CN(C)C1=CC=C(B(O)O)C=C1 RIIPFHVHLXPMHQ-UHFFFAOYSA-N 0.000 description 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000006323 alkenyl amino group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000002032 cellular defenses Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 210000000172 cytosol Anatomy 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- GSFDYMMFCGYFJF-UHFFFAOYSA-N diethyl 2-(bromomethyl)propanedioate Chemical compound CCOC(=O)C(CBr)C(=O)OCC GSFDYMMFCGYFJF-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 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
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000132 electrospray ionisation Methods 0.000 description 1
- 239000006274 endogenous ligand Substances 0.000 description 1
- 230000006353 environmental stress Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 1
- MCAHMSDENAOJFZ-BVXDHVRPSA-N herbimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](OC)[C@@H](OC)C[C@H](C)[C@@H](OC)C2=CC(=O)C=C1C2=O MCAHMSDENAOJFZ-BVXDHVRPSA-N 0.000 description 1
- 229930193320 herbimycin Natural products 0.000 description 1
- ACGUYXCXAPNIKK-UHFFFAOYSA-N hexachlorophene Chemical compound OC1=C(Cl)C=C(Cl)C(Cl)=C1CC1=C(O)C(Cl)=CC(Cl)=C1Cl ACGUYXCXAPNIKK-UHFFFAOYSA-N 0.000 description 1
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 1
- VJKYNWPQVZHJAR-UHFFFAOYSA-H hexasodium trisulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O VJKYNWPQVZHJAR-UHFFFAOYSA-H 0.000 description 1
- ROASJEHPZNKHOF-UHFFFAOYSA-N hexyl carbamate Chemical compound CCCCCCOC(N)=O ROASJEHPZNKHOF-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000007954 hypoxia Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 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
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- ZIYVHBGGAOATLY-UHFFFAOYSA-N methylmalonic acid Chemical compound OC(=O)C(C)C(O)=O ZIYVHBGGAOATLY-UHFFFAOYSA-N 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- DILRJUIACXKSQE-UHFFFAOYSA-N n',n'-dimethylethane-1,2-diamine Chemical compound CN(C)CCN DILRJUIACXKSQE-UHFFFAOYSA-N 0.000 description 1
- 210000004897 n-terminal region Anatomy 0.000 description 1
- DRHOWMRJAGBUHY-UHFFFAOYSA-N naphthalen-2-ylcarbamic acid Chemical compound C1=CC=CC2=CC(NC(=O)O)=CC=C21 DRHOWMRJAGBUHY-UHFFFAOYSA-N 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 230000006548 oncogenic transformation Effects 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 102000027450 oncoproteins Human genes 0.000 description 1
- 108091008819 oncoproteins Proteins 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000003998 progesterone receptors Human genes 0.000 description 1
- 108090000468 progesterone receptors Proteins 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000006432 protein unfolding Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 description 1
- 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
- GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
- UMLDUMMLRZFROX-UHFFFAOYSA-N pyridin-2-ylboronic acid Chemical compound OB(O)C1=CC=CC=N1 UMLDUMMLRZFROX-UHFFFAOYSA-N 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- WUOFQGMXQCSPPV-UHFFFAOYSA-N tributyl(1,3-thiazol-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=NC=CS1 WUOFQGMXQCSPPV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
- C07D473/32—Nitrogen atom
- C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Oncology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24934909P | 2009-10-07 | 2009-10-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PT2486039T true PT2486039T (pt) | 2016-09-06 |
Family
ID=43857159
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT108227182T PT2486039T (pt) | 2009-10-07 | 2010-10-07 | Derivados de purina úteis como inibidores de hsp90 |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US9328114B2 (https=) |
| EP (2) | EP3091019B1 (https=) |
| JP (3) | JP5941407B2 (https=) |
| KR (2) | KR101906568B1 (https=) |
| CN (3) | CN106083855B (https=) |
| AU (1) | AU2010303343B2 (https=) |
| BR (1) | BR112012008019A2 (https=) |
| CA (1) | CA2776308C (https=) |
| DK (1) | DK2486039T3 (https=) |
| EA (1) | EA029272B1 (https=) |
| ES (2) | ES2733131T3 (https=) |
| LT (1) | LT2486039T (https=) |
| MX (1) | MX340714B (https=) |
| NZ (2) | NZ599138A (https=) |
| PT (1) | PT2486039T (https=) |
| WO (1) | WO2011044394A1 (https=) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9403828B2 (en) | 2005-02-01 | 2016-08-02 | Sloan-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| US7834181B2 (en) | 2005-02-01 | 2010-11-16 | Slaon-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| WO2008005937A2 (en) | 2006-06-30 | 2008-01-10 | Sloan-Kettering Institute For Cancer Research | Treatment of neurodegenerative diseases through inhibiton of hsp90 |
| JP5941407B2 (ja) | 2009-10-07 | 2016-06-29 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Ｈｓｐ９０阻害剤 |
| CN103596955B (zh) | 2011-04-05 | 2016-11-16 | 索隆-基特林癌症研究协会 | Hsp90抑制剂 |
| JP6266506B2 (ja) | 2011-04-05 | 2018-01-24 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Ｈｓｐ９０阻害物質 |
| EA201490230A1 (ru) * | 2011-07-08 | 2014-06-30 | Слоан-Кеттеринг Инститьют Фор Кэнсер Рисерч | Применение меченых ингибиторов hsp90 |
| EP2972394A4 (en) | 2013-03-15 | 2016-11-02 | Sloan Kettering Inst Cancer | HSP90-DESIGNING AND THERAPY |
| SG11201601542SA (en) | 2013-08-16 | 2016-04-28 | Sloan Kettering Inst Cancer | Selective grp94 inhibitors and uses thereof |
| BR112016005199B1 (pt) | 2013-08-23 | 2022-02-22 | Neupharma, Inc | Certos compostos químicos, composições, e métodos |
| WO2015138039A1 (en) | 2013-12-23 | 2015-09-17 | Memorial Sloan-Kettering Cancer Center | Methods and reagents for radiolabeling |
| MX387627B (es) * | 2014-09-17 | 2025-03-18 | Memorial Sloan Kettering Cancer Center | Formación de imágenes de inflamación e infección dirigida a hsp90 y terapia |
| US20180280397A1 (en) | 2015-10-05 | 2018-10-04 | Memorial Sloan Kettering Cancer Center | Rational combination therapy for the treatment of cancer |
| WO2018035061A1 (en) | 2016-08-15 | 2018-02-22 | Neupharma, Inc. | Certain chemical entities, compositions, and methods |
| KR20190138871A (ko) * | 2017-04-24 | 2019-12-16 | 사무스 테라퓨틱스, 인코포레이티드 | Hsp90 저해제 경구 제형 및 관련 방법 |
| CN111683658A (zh) * | 2017-06-23 | 2020-09-18 | 萨缪斯治疗股份有限公司 | 用于创伤性脑损伤及其后遗症的多蛋白复合物抑制剂疗法 |
| TW202508595A (zh) | 2023-05-04 | 2025-03-01 | 美商銳新醫藥公司 | 用於ｒａｓ相關疾病或病症之組合療法 |
| US20250049810A1 (en) | 2023-08-07 | 2025-02-13 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| AU2024360465A1 (en) | 2023-10-12 | 2026-04-09 | Revolution Medicines, Inc. | Macrocyclic ras inhibitors |
| WO2025099111A1 (en) | 2023-11-10 | 2025-05-15 | Wella Germany Gmbh | New telescoping syntheses of 6-hydroxy-benzomorpholine (3,4-dihydro-2h-1,4-benzoxazin-6-ol) |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| TW202547461A (zh) | 2024-05-17 | 2025-12-16 | 美商銳新醫藥公司 | Ｒａｓ抑制劑 |
| WO2025255438A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026015801A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026050446A1 (en) | 2024-08-29 | 2026-03-05 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026072904A2 (en) | 2024-09-26 | 2026-04-02 | Revolution Medicines, Inc. | Compositions and methods for treating lung cancer |
Family Cites Families (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2287387C (en) | 1997-05-14 | 2010-02-16 | Sloan-Kettering Institute For Cancer Research | Methods and compositions for destruction of selected proteins |
| JP2002541255A (ja) | 1999-04-09 | 2002-12-03 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Ｈｅｒ族チロシンキナーゼの分解および／または阻害方法および組成物 |
| US7439359B2 (en) | 2000-11-02 | 2008-10-21 | Sloan-Kettering Institute For Cancer Research | Small molecule compositions for binding to hsp90 |
| WO2003037860A2 (en) * | 2001-10-30 | 2003-05-08 | Conforma Therapeutics Corporation | Purine analogs having hsp90-inhibiting activity |
| NL1019258C2 (nl) * | 2001-10-30 | 2003-05-02 | Iku Holding Montfoort Bv | Bevestigingsconstructie, in het bijzonder voor een buitenspiegel van een motorvoertuig. |
| EP1450784A4 (en) | 2001-11-09 | 2005-02-09 | Conforma Therapeutics Corp | HSP90-INHIBITABLE ZEARALANOL COMPOUNDS AND METHOD FOR THEIR PREPARATION AND USE |
| CN1649866A (zh) | 2002-02-28 | 2005-08-03 | 阿斯特拉曾尼卡有限公司 | 3－环状基－5－(含氮5－元环)甲基－噁唑烷酮衍生物及其作为抗菌药物的用途 |
| EP1620564A4 (en) | 2003-04-18 | 2008-03-12 | Cytovia Inc | METHOD FOR TREATING DISEASES RESPONSING TO APOPTOSIS INDUCTION AND SCREENING TESTS |
| MXPA06002997A (es) | 2003-09-18 | 2007-02-08 | Conforma Therapeutics Corp | Novedosos compuestos heterociclicos como inhibidores- hsp90. |
| US9403828B2 (en) | 2005-02-01 | 2016-08-02 | Sloan-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| US7834181B2 (en) | 2005-02-01 | 2010-11-16 | Slaon-Kettering Institute For Cancer Research | Small-molecule Hsp90 inhibitors |
| EP1913738A2 (en) | 2005-07-27 | 2008-04-23 | QUALCOMM Incorporated | System and method for forward link only messages |
| WO2007134298A2 (en) * | 2006-05-12 | 2007-11-22 | Myriad Genetics, Inc. | Therapeutic compounds and their use in cancer |
| WO2007143629A1 (en) | 2006-06-02 | 2007-12-13 | Nexgenix Pharmaceuticals | Treatment of neurofibromatosis with inhibitors of a signal transduction pathway |
| US20080053862A1 (en) | 2006-06-30 | 2008-03-06 | Sanford, L.P. | Interlocking Nestable Article Holder |
| WO2008005937A2 (en) | 2006-06-30 | 2008-01-10 | Sloan-Kettering Institute For Cancer Research | Treatment of neurodegenerative diseases through inhibiton of hsp90 |
| CL2007002994A1 (es) * | 2006-10-19 | 2008-02-08 | Wyeth Corp | Compuestos derivados heterociclicos que contienen sulfamoilo, inhibidores de hsp90; composicion farmaceutica; y uso para el tratamiento del cancer, tal como cancer de mama, de colon y prostata, entre otros. |
| WO2008115262A2 (en) | 2007-03-20 | 2008-09-25 | Curis, Inc. | Hsp90 inhibitors containing a zinc binding moiety |
| KR101313804B1 (ko) | 2007-03-20 | 2013-10-01 | 쿠리스 인코퍼레이션 | Ｈｓｐ９０ 억제제로서의 융합된 아미노 피리딘 |
| WO2009007399A1 (en) * | 2007-07-12 | 2009-01-15 | Crystax Pharmaceuticals, S.L. | New compounds as hsp90 inhibitors |
| WO2009042646A1 (en) | 2007-09-24 | 2009-04-02 | Curis, Inc. | Anti-proliferative agents |
| NZ586129A (en) | 2007-11-14 | 2012-06-29 | Myrexis Inc | Therapeutic compounds and their use in treating diseases and disorders |
| JP5941407B2 (ja) | 2009-10-07 | 2016-06-29 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Ｈｓｐ９０阻害剤 |
| CN103596955B (zh) | 2011-04-05 | 2016-11-16 | 索隆-基特林癌症研究协会 | Hsp90抑制剂 |
| JP6266506B2 (ja) | 2011-04-05 | 2018-01-24 | スローン − ケッタリング インスティチュート フォー キャンサー リサーチ | Ｈｓｐ９０阻害物質 |
| SG11201601542SA (en) | 2013-08-16 | 2016-04-28 | Sloan Kettering Inst Cancer | Selective grp94 inhibitors and uses thereof |
-
2010
- 2010-10-07 JP JP2012533327A patent/JP5941407B2/ja not_active Expired - Fee Related
- 2010-10-07 EP EP16171952.1A patent/EP3091019B1/en not_active Not-in-force
- 2010-10-07 AU AU2010303343A patent/AU2010303343B2/en not_active Ceased
- 2010-10-07 NZ NZ599138A patent/NZ599138A/en not_active IP Right Cessation
- 2010-10-07 BR BR112012008019A patent/BR112012008019A2/pt not_active IP Right Cessation
- 2010-10-07 NZ NZ625593A patent/NZ625593A/en not_active IP Right Cessation
- 2010-10-07 CA CA2776308A patent/CA2776308C/en not_active Expired - Fee Related
- 2010-10-07 LT LTEP10822718.2T patent/LT2486039T/lt unknown
- 2010-10-07 US US13/500,809 patent/US9328114B2/en active Active
- 2010-10-07 CN CN201610269904.3A patent/CN106083855B/zh not_active Expired - Fee Related
- 2010-10-07 KR KR1020127011546A patent/KR101906568B1/ko not_active Expired - Fee Related
- 2010-10-07 WO PCT/US2010/051872 patent/WO2011044394A1/en not_active Ceased
- 2010-10-07 EA EA201270535A patent/EA029272B1/ru not_active IP Right Cessation
- 2010-10-07 CN CN201610270112.8A patent/CN105924443A/zh active Pending
- 2010-10-07 ES ES16171952T patent/ES2733131T3/es active Active
- 2010-10-07 PT PT108227182T patent/PT2486039T/pt unknown
- 2010-10-07 MX MX2012004089A patent/MX340714B/es active IP Right Grant
- 2010-10-07 EP EP10822718.2A patent/EP2486039B1/en active Active
- 2010-10-07 DK DK10822718.2T patent/DK2486039T3/en active
- 2010-10-07 CN CN201080055473.1A patent/CN102639534A/zh active Pending
- 2010-10-07 KR KR1020187028594A patent/KR102129420B1/ko not_active Expired - Fee Related
- 2010-10-07 ES ES10822718.2T patent/ES2589403T3/es active Active
-
2016
- 2016-04-21 US US15/135,121 patent/US10172863B2/en active Active
- 2016-05-20 JP JP2016101964A patent/JP6326088B2/ja not_active Expired - Fee Related
-
2018
- 2018-02-15 JP JP2018024710A patent/JP6804483B2/ja not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| PT2486039T (pt) | Derivados de purina úteis como inibidores de hsp90 | |
| KR20120124428A (ko) | 치환된 피롤로-아미노피리미딘 화합물 | |
| US8541407B2 (en) | Substituted benzo-pyrido-triazolo-diazepine compounds | |
| MX2007012696A (es) | Inhibidores de adn-pk. | |
| CN111770926B (zh) | 三环化合物、组合物及其医药应用 | |
| AU2013204891B2 (en) | Purine derivatives useful as hsp90 inhibitors | |
| HK1230612A (en) | Purine derivatives useful as hsp90 inhibitors | |
| HK1230612B (zh) | 用作hsp90抑制劑的嘌呤衍生物 | |
| HK1230612A1 (en) | Purine derivatives useful as hsp90 inhibitors | |
| BRPI0610675A2 (pt) | inibidores de dna-pk |