JP2017519021A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2017519021A5 JP2017519021A5 JP2016574424A JP2016574424A JP2017519021A5 JP 2017519021 A5 JP2017519021 A5 JP 2017519021A5 JP 2016574424 A JP2016574424 A JP 2016574424A JP 2016574424 A JP2016574424 A JP 2016574424A JP 2017519021 A5 JP2017519021 A5 JP 2017519021A5
- Authority
- JP
- Japan
- Prior art keywords
- oxo
- diamino
- dihydroquinazolin
- carbonitrile
- pyrimidine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- -1 C Roarukiru Chemical group 0.000 claims description 82
- 150000001875 compounds Chemical class 0.000 claims description 75
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 150000003839 salts Chemical class 0.000 claims description 45
- 125000005843 halogen group Chemical group 0.000 claims description 30
- 239000001257 hydrogen Substances 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 23
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 22
- XVIAPHVAGFEFFN-UHFFFAOYSA-N pyrimidine-5-carbonitrile Chemical compound N#CC1=CN=CN=C1 XVIAPHVAGFEFFN-UHFFFAOYSA-N 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 19
- 125000001188 haloalkyl group Chemical group 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 17
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 16
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000002393 azetidinyl group Chemical group 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 10
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 6
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 125000003725 azepanyl group Chemical group 0.000 claims description 6
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 125000003566 oxetanyl group Chemical group 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims description 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 5
- 230000000694 effects Effects 0.000 claims description 5
- ODNMMTBDMCMWIA-KRWDZBQOSA-N 2,4-diamino-6-[(2S)-2-[3-(2-fluorophenyl)-5-methylsulfonyl-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=CC=CC(=C2C(N1C1=C(C=CC=C1)F)=O)S(=O)(=O)C ODNMMTBDMCMWIA-KRWDZBQOSA-N 0.000 claims description 4
- LTJDTZLNOJTXMS-KRWDZBQOSA-N 2,4-diamino-6-[(2S)-2-[3-(3-fluorophenyl)-5-methylsulfonyl-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC=C1)F)=O)S(=O)(=O)C LTJDTZLNOJTXMS-KRWDZBQOSA-N 0.000 claims description 4
- NRNZOLOAHSMLGT-IBGZPJMESA-N 2,4-diamino-6-[[(S)-cyclopropyl-[3-(2-fluorophenyl)-5-methylsulfonyl-4-oxoquinazolin-2-yl]methyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@H](C1=NC2=CC=CC(=C2C(N1C1=C(C=CC=C1)F)=O)S(=O)(=O)C)C1CC1 NRNZOLOAHSMLGT-IBGZPJMESA-N 0.000 claims description 4
- 125000001963 4 membered heterocyclic group Chemical group 0.000 claims description 4
- VBFRFRVPVIHNJU-HNNXBMFYSA-N 5-chloro-2-[(3R)-4-(2,6-diamino-5-chloropyrimidin-4-yl)morpholin-3-yl]-3-phenylquinazolin-4-one Chemical compound [H][C@]1(COCCN1C1=NC(N)=NC(N)=C1Cl)C1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1 VBFRFRVPVIHNJU-HNNXBMFYSA-N 0.000 claims description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 4
- 208000025324 B-cell acute lymphoblastic leukemia Diseases 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 claims description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 4
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 4
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 4
- 208000037538 Myelomonocytic Juvenile Leukemia Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 208000007660 Residual Neoplasm Diseases 0.000 claims description 4
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims description 4
- 208000016025 Waldenstroem macroglobulinemia Diseases 0.000 claims description 4
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 4
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 4
- 201000005992 juvenile myelomonocytic leukemia Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- XHDIMAWEQARQER-INIZCTEOSA-N 2,4-diamino-6-[(2S)-2-[3-(2,6-difluorophenyl)-5-methylsulfonyl-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=CC=CC(=C2C(N1C1=C(C=CC=C1F)F)=O)S(=O)(=O)C XHDIMAWEQARQER-INIZCTEOSA-N 0.000 claims description 2
- XZFQZIDTKMMORZ-KRWDZBQOSA-N 2,4-diamino-6-[(2S)-2-[3-(3,5-difluorophenyl)-5-fluoro-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)F XZFQZIDTKMMORZ-KRWDZBQOSA-N 0.000 claims description 2
- ULIPIDUOYUPPGA-SFHVURJKSA-N 2,4-diamino-6-[(2S)-2-[3-(3,5-difluorophenyl)-8-methyl-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=C(C=CC=C2C(N1C1=CC(=CC(=C1)F)F)=O)C ULIPIDUOYUPPGA-SFHVURJKSA-N 0.000 claims description 2
- UBCROLIANMOUOT-IBYPIGCZSA-N 2,4-diamino-6-[(2S)-2-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]-4-methoxypyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CC(C1)OC)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl UBCROLIANMOUOT-IBYPIGCZSA-N 0.000 claims description 2
- FCOTXTGOPHPHDV-INIZCTEOSA-N 2,4-diamino-6-[(2S)-2-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]azetidin-1-yl]pyrimidine-5-carbonitrile Chemical compound [H][C@]1(CCN1C1=C(C#N)C(N)=NC(N)=N1)C1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC(F)=CC(F)=C1 FCOTXTGOPHPHDV-INIZCTEOSA-N 0.000 claims description 2
- HNVQQPZDIGHQII-KRWDZBQOSA-N 2,4-diamino-6-[(2S)-2-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl HNVQQPZDIGHQII-KRWDZBQOSA-N 0.000 claims description 2
- ZBHMSTGNEZJWSQ-KRWDZBQOSA-N 2,4-diamino-6-[(2S)-2-[5-chloro-3-(3,5-difluorophenyl)-8-methyl-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=C(C=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl)C ZBHMSTGNEZJWSQ-KRWDZBQOSA-N 0.000 claims description 2
- FFZIQDWOFOXVDY-SFHVURJKSA-N 2,4-diamino-6-[(2S)-2-[5-chloro-3-(3-cyano-5-fluorophenyl)-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)C#N)=O)Cl FFZIQDWOFOXVDY-SFHVURJKSA-N 0.000 claims description 2
- DCUIDXPXCJSQIC-ACJLOTCBSA-N 2,4-diamino-6-[(2S,4R)-2-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-4-methylpyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](C[C@H](C1)C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl DCUIDXPXCJSQIC-ACJLOTCBSA-N 0.000 claims description 2
- UVECEKSYBYUSKF-PXAZEXFGSA-N 2,4-diamino-6-[(2S,4R)-2-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]-4-fluoropyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](C[C@H](C1)F)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl UVECEKSYBYUSKF-PXAZEXFGSA-N 0.000 claims description 2
- GWMBPACLSXYONO-NRFANRHFSA-N 2,4-diamino-6-[[(S)-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-phenylmethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C1=CC=CC=C1)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl GWMBPACLSXYONO-NRFANRHFSA-N 0.000 claims description 2
- NRJSHKSODUMLII-FQEVSTJZSA-N 2,4-diamino-6-[[(S)-[3-(3-cyano-5-fluorophenyl)-5-methyl-4-oxoquinazolin-2-yl]-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C1CC1)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)C#N)=O)C NRJSHKSODUMLII-FQEVSTJZSA-N 0.000 claims description 2
- HARCUZQNOFNGEA-SFHVURJKSA-N 2,4-diamino-6-[[(S)-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C1CC1)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl HARCUZQNOFNGEA-SFHVURJKSA-N 0.000 claims description 2
- DRDYADBTFZGAJP-SFHVURJKSA-N 2,4-diamino-6-[[(S)-cyclopropyl-[3-(2,6-difluorophenyl)-5-methylsulfonyl-4-oxoquinazolin-2-yl]methyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@H](C1=NC2=CC=CC(=C2C(N1C1=C(C=CC=C1F)F)=O)S(=O)(=O)C)C1CC1 DRDYADBTFZGAJP-SFHVURJKSA-N 0.000 claims description 2
- SJZQRPNTRXQNBH-SFHVURJKSA-N 2,4-diamino-6-[[(S)-cyclopropyl-[3-(3,5-difluorophenyl)-5-fluoro-4-oxoquinazolin-2-yl]methyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@H](C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)F)C1CC1 SJZQRPNTRXQNBH-SFHVURJKSA-N 0.000 claims description 2
- HTNPZVQEQLIDFG-IBGZPJMESA-N 2,4-diamino-6-[[(S)-cyclopropyl-[3-(3,5-difluorophenyl)-5-methyl-4-oxoquinazolin-2-yl]methyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@H](C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)C)C1CC1 HTNPZVQEQLIDFG-IBGZPJMESA-N 0.000 claims description 2
- OBKJDCQVRLWCPF-IBGZPJMESA-N 2,4-diamino-6-[[(S)-cyclopropyl-[3-(3-fluorophenyl)-5-methylsulfonyl-4-oxoquinazolin-2-yl]methyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@H](C1=NC2=CC=CC(=C2C(N1C1=CC(=CC=C1)F)=O)S(=O)(=O)C)C1CC1 OBKJDCQVRLWCPF-IBGZPJMESA-N 0.000 claims description 2
- WJJDKGUKVMJLCF-SFHVURJKSA-N 2,4-diamino-6-[[(S)-cyclopropyl-[5-fluoro-3-(3-fluorophenyl)-4-oxoquinazolin-2-yl]methyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@H](C1=NC2=CC=CC(=C2C(N1C1=CC(=CC=C1)F)=O)F)C1CC1 WJJDKGUKVMJLCF-SFHVURJKSA-N 0.000 claims description 2
- KRTLGTDEKUDJTP-SFHVURJKSA-N 2,4-diamino-6-[[(S)-cyclopropyl-[6-fluoro-3-(3-fluorophenyl)-4-oxoquinazolin-2-yl]methyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@H](C1=NC2=CC=C(C=C2C(N1C1=CC(=CC=C1)F)=O)F)C1CC1 KRTLGTDEKUDJTP-SFHVURJKSA-N 0.000 claims description 2
- VLLAMKWYMNGXCR-SFHVURJKSA-N 2-[(2S)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-2-yl]-3-[3-(difluoromethyl)phenyl]-4-oxoquinazoline-8-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N1[C@@H](CCC1)C1=NC2=C(C=CC=C2C(N1C1=CC(=CC=C1)C(F)F)=O)C#N)C#N)N VLLAMKWYMNGXCR-SFHVURJKSA-N 0.000 claims description 2
- PTQDJUFYSUQXTD-SFHVURJKSA-N 2-[(2S)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-2-yl]-4-oxo-3-phenylquinazoline-8-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N1[C@@H](CCC1)C1=NC2=C(C=CC=C2C(N1C1=CC=CC=C1)=O)C#N)C#N)N PTQDJUFYSUQXTD-SFHVURJKSA-N 0.000 claims description 2
- TWHKASHPBXEZBH-IBGZPJMESA-N 2-[(S)-cyclopropyl-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]methyl]-3-[3-(difluoromethyl)-5-fluorophenyl]-4-oxoquinazoline-5-carbonitrile Chemical compound C1(CC1)[C@@H](C1=NC=2C=CC=C(C=2C(N1C1=CC(=CC(=C1)F)C(F)F)=O)C#N)NC1=NC(=NC(=C1C#N)N)N TWHKASHPBXEZBH-IBGZPJMESA-N 0.000 claims description 2
- ORFXHKONYOHFGX-IBGZPJMESA-N 2-[(S)-cyclopropyl-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]methyl]-4-oxo-3-phenylquinazoline-5-carbonitrile Chemical compound C1(CC1)[C@@H](C1=NC=2C=CC=C(C=2C(N1C1=CC=CC=C1)=O)C#N)NC1=NC(=NC(=C1C#N)N)N ORFXHKONYOHFGX-IBGZPJMESA-N 0.000 claims description 2
- ALGSGQZRYDSPGW-IBGZPJMESA-N 2-[(S)-cyclopropyl-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]methyl]-6-fluoro-3-(3-fluorophenyl)-4-oxoquinazoline-8-carbonitrile Chemical compound C1(CC1)[C@@H](C1=NC2=C(C=C(C=C2C(N1C1=CC(=CC=C1)F)=O)F)C#N)NC1=NC(=NC(=C1C#N)N)N ALGSGQZRYDSPGW-IBGZPJMESA-N 0.000 claims description 2
- DUJZMFOTBPIMFE-IBGZPJMESA-N 2-[(S)-cyclopropyl-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]methyl]-6-fluoro-4-oxo-3-phenylquinazoline-8-carbonitrile Chemical compound C1(CC1)[C@@H](C1=NC2=C(C=C(C=C2C(N1C1=CC=CC=C1)=O)F)C#N)NC1=NC(=NC(=C1C#N)N)N DUJZMFOTBPIMFE-IBGZPJMESA-N 0.000 claims description 2
- CRCZCZPIXMNRNN-SFHVURJKSA-N 2-[(S)-cyclopropyl-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]methyl]-8-fluoro-4-oxo-3-phenylquinazoline-5-carbonitrile Chemical compound C1(CC1)[C@@H](C1=NC=2C(=CC=C(C=2C(N1C1=CC=CC=C1)=O)C#N)F)NC1=NC(=NC(=C1C#N)N)N CRCZCZPIXMNRNN-SFHVURJKSA-N 0.000 claims description 2
- GNZXPAYCWAHIQH-ACJLOTCBSA-N 2-amino-N-[(3R,5S)-5-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-3-yl]acetamide Chemical compound NCC(=O)N[C@H]1CN([C@@H](C1)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl)C1=NC(=NC(=C1C#N)N)N GNZXPAYCWAHIQH-ACJLOTCBSA-N 0.000 claims description 2
- WDKDKOGDFAMTQW-FQEVSTJZSA-N 4-[2-[(2S)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-2-yl]-4-oxo-3-phenylquinazolin-5-yl]butanoic acid Chemical compound NC1=NC(=C(C(=N1)N1[C@@H](CCC1)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)CCCC(=O)O)C#N)N WDKDKOGDFAMTQW-FQEVSTJZSA-N 0.000 claims description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 2
- 206010073128 Anaplastic oligodendroglioma Diseases 0.000 claims description 2
- 206010003571 Astrocytoma Diseases 0.000 claims description 2
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 2
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 2
- 206010005003 Bladder cancer Diseases 0.000 claims description 2
- 206010005949 Bone cancer Diseases 0.000 claims description 2
- 208000018084 Bone neoplasm Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 2
- HLUNHEREQCLTFM-UHFFFAOYSA-N C1(CC1)C1=NC2=C(C=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1CCCC1)F Chemical compound C1(CC1)C1=NC2=C(C=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1CCCC1)F HLUNHEREQCLTFM-UHFFFAOYSA-N 0.000 claims description 2
- YFKCOAMZABHFQB-UHFFFAOYSA-N C1(CC1)C1=NC2=C(C=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1CCCCC1)F Chemical compound C1(CC1)C1=NC2=C(C=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1CCCCC1)F YFKCOAMZABHFQB-UHFFFAOYSA-N 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000032612 Glial tumor Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 2
- 201000007224 Myeloproliferative neoplasm Diseases 0.000 claims description 2
- XCUAIINAJCDIPM-XVFCMESISA-N N(4)-hydroxycytidine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=NO)C=C1 XCUAIINAJCDIPM-XVFCMESISA-N 0.000 claims description 2
- DNIGJQZANIQMHX-PXAZEXFGSA-N N-[(3R,5S)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)-5-[3-(3,5-difluorophenyl)-5-fluoro-4-oxoquinazolin-2-yl]pyrrolidin-3-yl]-2,2-difluoroacetamide Chemical compound NC1=NC(=C(C(=N1)N1C[C@@H](C[C@H]1C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)F)NC(C(F)F)=O)C#N)N DNIGJQZANIQMHX-PXAZEXFGSA-N 0.000 claims description 2
- GHAOVOJGFBIETP-PXAZEXFGSA-N N-[(3R,5S)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)-5-[3-[3-(difluoromethyl)-5-fluorophenyl]-5-fluoro-4-oxoquinazolin-2-yl]pyrrolidin-3-yl]-2,2-difluoroacetamide Chemical compound NC1=NC(=C(C(=N1)N1C[C@@H](C[C@H]1C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)C(F)F)=O)F)NC(C(F)F)=O)C#N)N GHAOVOJGFBIETP-PXAZEXFGSA-N 0.000 claims description 2
- IEBFTUYANMFVIK-PXAZEXFGSA-N N-[(3R,5S)-5-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-3-yl]-2,2-difluoroacetamide Chemical compound ClC1=C2C(N(C(=NC2=CC=C1)[C@@H]1C[C@H](CN1C1=NC(=NC(=C1C#N)N)N)NC(C(F)F)=O)C1=CC=CC=C1)=O IEBFTUYANMFVIK-PXAZEXFGSA-N 0.000 claims description 2
- ZSKCJMYWUFPTLS-IERDGZPVSA-N N-[(3R,5S)-5-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-3-yl]-2-cyclopropylacetamide Chemical compound ClC1=C2C(N(C(=NC2=CC=C1)[C@@H]1C[C@H](CN1C1=NC(=NC(=C1C#N)N)N)NC(CC1CC1)=O)C1=CC=CC=C1)=O ZSKCJMYWUFPTLS-IERDGZPVSA-N 0.000 claims description 2
- WMEMOTLPCYXHNW-KDOFPFPSSA-N N-[(3R,5S)-5-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-3-yl]-2,2-difluoro-N-methylacetamide Chemical compound ClC1=C2C(N(C(=NC2=CC=C1)[C@@H]1C[C@H](CN1C1=NC(=NC(=C1C#N)N)N)N(C(C(F)F)=O)C)C1=CC(=CC(=C1)F)F)=O WMEMOTLPCYXHNW-KDOFPFPSSA-N 0.000 claims description 2
- MAWAWGAXNNTZIA-PXAZEXFGSA-N N-[(3R,5S)-5-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-3-yl]-2,2-difluoroacetamide Chemical compound ClC1=C2C(N(C(=NC2=CC=C1)[C@@H]1C[C@H](CN1C1=NC(=NC(=C1C#N)N)N)NC(C(F)F)=O)C1=CC(=CC(=C1)F)F)=O MAWAWGAXNNTZIA-PXAZEXFGSA-N 0.000 claims description 2
- FCRZUCQJLYMRQL-PXAZEXFGSA-N N-[(3R,5S)-5-[5-chloro-3-[3-(difluoromethyl)-5-fluorophenyl]-4-oxoquinazolin-2-yl]-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-3-yl]-2,2-difluoroacetamide Chemical compound ClC1=C2C(N(C(=NC2=CC=C1)[C@@H]1C[C@H](CN1C1=NC(=NC(=C1C#N)N)N)NC(C(F)F)=O)C1=CC(=CC(=C1)F)C(F)F)=O FCRZUCQJLYMRQL-PXAZEXFGSA-N 0.000 claims description 2
- OTYATIHHKUGQAX-SJCJKPOMSA-N N-[(3S,5S)-5-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-3-yl]-2,2,2-trifluoroacetamide Chemical compound ClC1=C2C(N(C(=NC2=CC=C1)[C@@H]1C[C@@H](CN1C1=NC(=NC(=C1C#N)N)N)NC(C(F)(F)F)=O)C1=CC=CC=C1)=O OTYATIHHKUGQAX-SJCJKPOMSA-N 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims description 2
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 206010038389 Renal cancer Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 206010042971 T-cell lymphoma Diseases 0.000 claims description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 2
- 206010043561 Thrombocytopenic purpura Diseases 0.000 claims description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 claims description 2
- 208000030002 adult glioblastoma Diseases 0.000 claims description 2
- 206010002224 anaplastic astrocytoma Diseases 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 201000007455 central nervous system cancer Diseases 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 2
- 230000001066 destructive effect Effects 0.000 claims description 2
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 claims description 2
- 201000003444 follicular lymphoma Diseases 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 208000005017 glioblastoma Diseases 0.000 claims description 2
- 201000010536 head and neck cancer Diseases 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 230000028993 immune response Effects 0.000 claims description 2
- 230000005764 inhibitory process Effects 0.000 claims description 2
- 201000010982 kidney cancer Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 201000007924 marginal zone B-cell lymphoma Diseases 0.000 claims description 2
- 208000021937 marginal zone lymphoma Diseases 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 206010028417 myasthenia gravis Diseases 0.000 claims description 2
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 2
- 201000002120 neuroendocrine carcinoma Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 210000004180 plasmocyte Anatomy 0.000 claims description 2
- 229920001184 polypeptide Polymers 0.000 claims description 2
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 2
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 2
- 230000000750 progressive effect Effects 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims 8
- 125000001424 substituent group Chemical group 0.000 claims 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 2
- 125000005842 heteroatom Chemical group 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 239000001301 oxygen Chemical group 0.000 claims 2
- 229910052760 oxygen Inorganic materials 0.000 claims 2
- 229910052717 sulfur Chemical group 0.000 claims 2
- 239000011593 sulfur Chemical group 0.000 claims 2
- NPMSINYHIKDDQA-KRWDZBQOSA-N 2,4-diamino-6-[(2S)-2-[8-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]pyrrolidin-1-yl]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N1[C@@H](CCC1)C1=NC2=C(C=CC=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl NPMSINYHIKDDQA-KRWDZBQOSA-N 0.000 claims 1
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 1
- IKRRDODTDUOTPM-INIZCTEOSA-N 3-[5,8-dichloro-2-[(2S)-1-(2,6-diamino-5-cyanopyrimidin-4-yl)pyrrolidin-2-yl]-4-oxoquinazolin-3-yl]benzenesulfonamide Chemical compound ClC1=C2C(N(C(=NC2=C(C=C1)Cl)[C@H]1N(CCC1)C1=NC(=NC(=C1C#N)N)N)C=1C=C(C=CC=1)S(=O)(=O)N)=O IKRRDODTDUOTPM-INIZCTEOSA-N 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 210000004027 cell Anatomy 0.000 claims 1
- 125000005349 heteroarylcycloalkyl group Chemical group 0.000 claims 1
- 230000035755 proliferation Effects 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 description 12
- 125000000547 substituted alkyl group Chemical group 0.000 description 10
- 125000006655 (C3-C8) heteroaryl group Chemical group 0.000 description 5
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 239000012453 solvate Substances 0.000 description 4
- 125000003107 substituted aryl group Chemical group 0.000 description 4
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 4
- 125000005275 alkylenearyl group Chemical group 0.000 description 2
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 description 2
- 238000004806 packaging method and process Methods 0.000 description 2
- OAADYFAEHSXSKP-KRWDZBQOSA-N (3S)-3-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-3-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]-N,N-dimethylpropanamide Chemical compound ClC1=C2C(N(C(=NC2=CC=C1)[C@H](CC(=O)N(C)C)NC1=NC(=NC(=C1C#N)N)N)C1=CC=CC=C1)=O OAADYFAEHSXSKP-KRWDZBQOSA-N 0.000 description 1
- CXUXZTSEZPUEOT-KRWDZBQOSA-N (3S)-3-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]-3-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]-N,N-dimethylpropanamide Chemical compound ClC1=C2C(N(C(=NC2=CC=C1)[C@H](CC(=O)N(C)C)NC1=NC(=NC(=C1C#N)N)N)C1=CC(=CC(=C1)F)F)=O CXUXZTSEZPUEOT-KRWDZBQOSA-N 0.000 description 1
- OKIQNDSPZILKID-INIZCTEOSA-N 2,4-diamino-6-[(2S)-2-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)azetidin-1-yl]pyrimidine-5-carbonitrile Chemical compound [H][C@]1(CCN1C1=C(C#N)C(N)=NC(N)=N1)C1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1 OKIQNDSPZILKID-INIZCTEOSA-N 0.000 description 1
- JXCDNVIEVDKJRN-INIZCTEOSA-N 2,4-diamino-6-[[(1S)-1-[3-(3,5-difluorophenyl)-4-oxo-5-(3-pyrrolidin-1-ylpropyl)quinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)CCCN1CCCC1 JXCDNVIEVDKJRN-INIZCTEOSA-N 0.000 description 1
- LCSYWUOYYCCHSB-INIZCTEOSA-N 2,4-diamino-6-[[(1S)-1-[3-(3-fluorophenyl)-4-oxo-5-(2-pyrrolidin-1-ylethylsulfonyl)quinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC=C1)F)=O)S(=O)(=O)CCN1CCCC1 LCSYWUOYYCCHSB-INIZCTEOSA-N 0.000 description 1
- PCKVTZPTNOKKES-LBPRGKRZSA-N 2,4-diamino-6-[[(1S)-1-[3-(3-fluorophenyl)-5-(2-hydroxyethylsulfanyl)-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC=C1)F)=O)SCCO PCKVTZPTNOKKES-LBPRGKRZSA-N 0.000 description 1
- CTPWEQCZGKUOAM-LBPRGKRZSA-N 2,4-diamino-6-[[(1S)-1-[3-(3-fluorophenyl)-5-(2-hydroxyethylsulfonyl)-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC=C1)F)=O)S(=O)(=O)CCO CTPWEQCZGKUOAM-LBPRGKRZSA-N 0.000 description 1
- TXQXSAQSBKUYOK-QFIPXVFZSA-N 2,4-diamino-6-[[(1S)-1-[4-oxo-3-phenyl-5-[2-(4-phenylpiperazin-1-yl)ethoxy]quinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)OCCN1CCN(CC1)C1=CC=CC=C1 TXQXSAQSBKUYOK-QFIPXVFZSA-N 0.000 description 1
- STZQMXZKGRXGAY-INIZCTEOSA-N 2,4-diamino-6-[[(1S)-1-[4-oxo-3-phenyl-5-[3-(2,2,6,6-tetrafluoromorpholin-4-yl)propyl]quinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C[C@H](NC1=C(C#N)C(N)=NC(N)=N1)C1=NC2=CC=CC(CCCN3CC(F)(F)OC(F)(F)C3)=C2C(=O)N1C1=CC=CC=C1 STZQMXZKGRXGAY-INIZCTEOSA-N 0.000 description 1
- MURIQUGIJNEHHV-INIZCTEOSA-N 2,4-diamino-6-[[(1S)-1-[4-oxo-5-[2-(2-oxopyrrolidin-1-yl)ethoxy]-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C[C@H](NC1=C(C#N)C(N)=NC(N)=N1)C1=NC2=CC=CC(OCCN3CCCC3=O)=C2C(=O)N1C1=CC=CC=C1 MURIQUGIJNEHHV-INIZCTEOSA-N 0.000 description 1
- GOMMYXKEKBXOGQ-INIZCTEOSA-N 2,4-diamino-6-[[(1S)-1-[5-(2-morpholin-4-yl-2-oxoethoxy)-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)OCC(=O)N1CCOCC1 GOMMYXKEKBXOGQ-INIZCTEOSA-N 0.000 description 1
- INIOPDJHPWFPSY-KRWDZBQOSA-N 2,4-diamino-6-[[(1S)-1-[5-(2-morpholin-4-ylethoxy)-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)OCCN1CCOCC1 INIOPDJHPWFPSY-KRWDZBQOSA-N 0.000 description 1
- DKCQVTGWFQVMMV-IBGZPJMESA-N 2,4-diamino-6-[[(1S)-1-[5-(3-cyclohexylpropyl)-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C[C@H](NC1=NC(N)=NC(N)=C1C#N)C1=NC2=CC=CC(CCCC3CCCCC3)=C2C(=O)N1C1=CC=CC=C1 DKCQVTGWFQVMMV-IBGZPJMESA-N 0.000 description 1
- OFGZBSYIKRDFFE-SFHVURJKSA-N 2,4-diamino-6-[[(1S)-1-[5-(3-morpholin-4-ylpropyl)-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1CCOCC1 OFGZBSYIKRDFFE-SFHVURJKSA-N 0.000 description 1
- FHWXPJCOSJJGHR-HNNXBMFYSA-N 2,4-diamino-6-[[(1S)-1-[5-(benzenesulfonyl)-3-(3-fluorophenyl)-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC=C1)F)=O)S(=O)(=O)C1=CC=CC=C1 FHWXPJCOSJJGHR-HNNXBMFYSA-N 0.000 description 1
- OXRCQIZHTARIJU-HNNXBMFYSA-N 2,4-diamino-6-[[(1S)-1-[5-[(3-methyloxetan-3-yl)methoxy]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)OCC1(COC1)C OXRCQIZHTARIJU-HNNXBMFYSA-N 0.000 description 1
- SPLZMKYVCXYTBZ-ZENAZSQFSA-N 2,4-diamino-6-[[(1S)-1-[5-[2-(1-methylpyrrolidin-2-yl)ethoxy]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)OCCC1N(CCC1)C SPLZMKYVCXYTBZ-ZENAZSQFSA-N 0.000 description 1
- OPAKIOVHYXWDSV-INIZCTEOSA-N 2,4-diamino-6-[[(1S)-1-[5-[2-(2-methylimidazol-1-yl)ethoxy]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)OCCN1C(=NC=C1)C OPAKIOVHYXWDSV-INIZCTEOSA-N 0.000 description 1
- GSXPHTXQKLMCAU-HNNXBMFYSA-N 2,4-diamino-6-[[(1S)-1-[5-[2-(dimethylamino)ethoxy]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C[C@H](NC1=C(C#N)C(N)=NC(N)=N1)C1=NC2=CC=CC(OCCN(C)C)=C2C(=O)N1C1=CC=CC=C1 GSXPHTXQKLMCAU-HNNXBMFYSA-N 0.000 description 1
- GKZRKMFWLGFQKM-IBGZPJMESA-N 2,4-diamino-6-[[(1S)-1-[5-[3-(2,2-dimethylmorpholin-4-yl)propyl]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1CC(OCC1)(C)C GKZRKMFWLGFQKM-IBGZPJMESA-N 0.000 description 1
- XTNPMHGEXROTSP-SFHVURJKSA-N 2,4-diamino-6-[[(1S)-1-[5-[3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)propyl]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C1OCC11CN(C1)CCCC1=C2C(N(C(=NC2=CC=C1)[C@H](C)NC1=NC(=NC(=C1C#N)N)N)C1=CC=CC=C1)=O XTNPMHGEXROTSP-SFHVURJKSA-N 0.000 description 1
- ICRKSHNYKMPASN-IBGZPJMESA-N 2,4-diamino-6-[[(1S)-1-[5-[3-(2-oxa-7-azaspiro[3.4]octan-7-yl)propyl]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C1OCC11CN(CC1)CCCC1=C2C(N(C(=NC2=CC=C1)[C@H](C)NC1=NC(=NC(=C1C#N)N)N)C1=CC=CC=C1)=O ICRKSHNYKMPASN-IBGZPJMESA-N 0.000 description 1
- UINSHMNWEIPLPN-FQEVSTJZSA-N 2,4-diamino-6-[[(1S)-1-[5-[3-(2-oxa-7-azaspiro[3.5]nonan-7-yl)propyl]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C1OCC11CCN(CC1)CCCC1=C2C(N(C(=NC2=CC=C1)[C@H](C)NC1=NC(=NC(=C1C#N)N)N)C1=CC=CC=C1)=O UINSHMNWEIPLPN-FQEVSTJZSA-N 0.000 description 1
- AIFOBPZFPHKWPN-KRWDZBQOSA-N 2,4-diamino-6-[[(1S)-1-[5-[3-(3,3-difluoropyrrolidin-1-yl)propyl]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1CC(CC1)(F)F AIFOBPZFPHKWPN-KRWDZBQOSA-N 0.000 description 1
- JJACAJXECQNVCV-IBGZPJMESA-N 2,4-diamino-6-[[(1S)-1-[5-[3-(3,3-dimethylmorpholin-4-yl)propyl]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1C(COCC1)(C)C JJACAJXECQNVCV-IBGZPJMESA-N 0.000 description 1
- BHGPJHIOJPTGHQ-MHJFOBGBSA-N 2,4-diamino-6-[[(1S)-1-[5-[3-(3,5-dimethylmorpholin-4-yl)propyl]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C[C@H](NC1=C(C#N)C(N)=NC(N)=N1)C1=NC2=CC=CC(CCCN3C(C)COCC3C)=C2C(=O)N1C1=CC=CC=C1 BHGPJHIOJPTGHQ-MHJFOBGBSA-N 0.000 description 1
- ARJICZONPWDDOJ-SFHVURJKSA-N 2,4-diamino-6-[[(1S)-1-[5-[3-(4,4-difluoropiperidin-1-yl)propyl]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)CCCN1CCC(CC1)(F)F ARJICZONPWDDOJ-SFHVURJKSA-N 0.000 description 1
- UOANVUBBOCFHED-HNNXBMFYSA-N 2,4-diamino-6-[[(1S)-1-[5-[3-hydroxy-2-(hydroxymethyl)-2-methylpropoxy]-4-oxo-3-phenylquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)OCC(CO)(C)CO UOANVUBBOCFHED-HNNXBMFYSA-N 0.000 description 1
- RKSQVRXOGZFTNA-AWEZNQCLSA-N 2,4-diamino-6-[[(1S)-1-[5-cyclopentylsulfonyl-3-(3-fluorophenyl)-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)N)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC=C1)F)=O)S(=O)(=O)C1CCCC1 RKSQVRXOGZFTNA-AWEZNQCLSA-N 0.000 description 1
- TXJHXFSNTZWCEU-LBPRGKRZSA-N 2-[(1S)-1-[(2-amino-5-iodo-6-methylpyrimidin-4-yl)amino]ethyl]-5-chloro-3-phenylquinazolin-4-one Chemical compound NC1=NC(=C(C(=N1)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl)I)C TXJHXFSNTZWCEU-LBPRGKRZSA-N 0.000 description 1
- YSZUXVKHXNXXLU-VIFPVBQESA-N 2-[(1S)-1-[(5-acetyl-2,6-diaminopyrimidin-4-yl)amino]ethyl]-5-chloro-3-(3,5-difluorophenyl)quinazolin-4-one Chemical compound C(C)(=O)C=1C(=NC(=NC=1N)N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl YSZUXVKHXNXXLU-VIFPVBQESA-N 0.000 description 1
- LKNVBFDROWOHEN-VIFPVBQESA-N 2-[(1S)-1-[(6-amino-5-bromo-2-methylpyrimidin-4-yl)amino]ethyl]-5-chloro-3-(3,5-difluorophenyl)quinazolin-4-one Chemical compound C[C@H](NC1=C(Br)C(N)=NC(C)=N1)C1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC(F)=CC(F)=C1 LKNVBFDROWOHEN-VIFPVBQESA-N 0.000 description 1
- GUALVYVRTVNIKR-NSHDSACASA-N 2-[(1S)-1-[(6-amino-5-bromo-2-methylpyrimidin-4-yl)amino]ethyl]-5-chloro-3-phenylquinazolin-4-one Chemical compound NC1=C(C(=NC(=N1)C)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl)Br GUALVYVRTVNIKR-NSHDSACASA-N 0.000 description 1
- ZQJYJSACBKJFQX-NSHDSACASA-N 2-amino-4-chloro-6-[[(1S)-1-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)Cl)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl ZQJYJSACBKJFQX-NSHDSACASA-N 0.000 description 1
- MFVIGWDJMOXJOT-JTQLQIEISA-N 2-amino-4-chloro-6-[[(1S)-1-(5-chloro-8-fluoro-4-oxo-3-phenylquinazolin-2-yl)ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)Cl)C#N)N[C@@H](C)C1=NC2=C(C=CC(=C2C(N1C1=CC=CC=C1)=O)Cl)F MFVIGWDJMOXJOT-JTQLQIEISA-N 0.000 description 1
- DYELZWBIVBYNMV-VIFPVBQESA-N 2-amino-4-chloro-6-[[(1S)-1-[3-(3,5-difluorophenyl)-5-fluoro-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)Cl)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)F DYELZWBIVBYNMV-VIFPVBQESA-N 0.000 description 1
- OJXCRLCQACFFMY-VIFPVBQESA-N 2-amino-4-chloro-6-[[(1S)-1-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile Chemical compound NC1=NC(=C(C(=N1)Cl)C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl OJXCRLCQACFFMY-VIFPVBQESA-N 0.000 description 1
- BYYCWNZDROLLCO-HNNXBMFYSA-N 2-amino-4-chloro-6-[[(1S)-1-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]propyl]amino]pyrimidine-5-carbonitrile Chemical compound CC[C@H](NC1=NC(N)=NC(Cl)=C1C#N)C1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC(F)=CC(F)=C1 BYYCWNZDROLLCO-HNNXBMFYSA-N 0.000 description 1
- UWPJENNPLNBWKZ-LBPRGKRZSA-N 3-[2-[(1S)-1-[(2,6-diamino-5-chloropyrimidin-4-yl)amino]ethyl]-4-oxo-3-phenylquinazolin-5-yl]propanamide Chemical compound NC1=NC(=C(C(=N1)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)CCC(=O)N)Cl)N UWPJENNPLNBWKZ-LBPRGKRZSA-N 0.000 description 1
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- JWLOUTWEPRZGNU-LBPRGKRZSA-N 4-[2-[(1S)-1-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]ethyl]-3-(3,5-difluorophenyl)-4-oxoquinazolin-5-yl]butanoic acid Chemical compound NC1=NC(=C(C(=N1)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)CCCC(=O)O)C#N)N JWLOUTWEPRZGNU-LBPRGKRZSA-N 0.000 description 1
- OODYZSAGYNAGNM-AWEZNQCLSA-N 4-[2-[(1S)-1-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]ethyl]-4-oxo-3-phenylquinazolin-5-yl]butanoic acid Chemical compound NC1=NC(=C(C(=N1)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)CCCC(=O)O)C#N)N OODYZSAGYNAGNM-AWEZNQCLSA-N 0.000 description 1
- CIYIAGNLSXJOJR-NSHDSACASA-N 4-amino-2-chloro-6-[[(1S)-1-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)ethyl]amino]pyrimidine-5-carbonitrile Chemical compound C[C@H](NC1=NC(Cl)=NC(N)=C1C#N)C1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1 CIYIAGNLSXJOJR-NSHDSACASA-N 0.000 description 1
- ZOCVIIWPJLLOSN-NSHDSACASA-N 4-amino-6-[[(1S)-1-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)ethyl]amino]-2-fluoropyrimidine-5-carbonitrile Chemical compound NC1=NC(=NC(=C1C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl)F ZOCVIIWPJLLOSN-NSHDSACASA-N 0.000 description 1
- HQZOOVIDFNMEIC-LBPRGKRZSA-N 4-amino-6-[[(1S)-1-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)ethyl]amino]-2-methylpyrimidine-5-carbonitrile Chemical compound NC1=NC(=NC(=C1C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl)C HQZOOVIDFNMEIC-LBPRGKRZSA-N 0.000 description 1
- PKRWLPKCJUWDMD-JTQLQIEISA-N 4-amino-6-[[(1S)-1-[5-chloro-3-(3,5-difluorophenyl)-4-oxoquinazolin-2-yl]ethyl]amino]-2-methylpyrimidine-5-carbonitrile Chemical compound NC1=NC(=NC(=C1C#N)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC(=CC(=C1)F)F)=O)Cl)C PKRWLPKCJUWDMD-JTQLQIEISA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- DFDCUHGDHCOYEJ-UHFFFAOYSA-N FC=1C=CC(=C2C(N(C=NC12)C1=CC=CC=C1)=O)CCCN1CCCC1 Chemical compound FC=1C=CC(=C2C(N(C=NC12)C1=CC=CC=C1)=O)CCCN1CCCC1 DFDCUHGDHCOYEJ-UHFFFAOYSA-N 0.000 description 1
- FBAQLKQDLGQNHD-UHFFFAOYSA-N N#CC1=CN=C(N(CCC2)C2C(N(C2=CC(F)=CC(F)=C2)C(C2=CC=C3)=O)=NC2=C3Cl)N=C1 Chemical compound N#CC1=CN=C(N(CCC2)C2C(N(C2=CC(F)=CC(F)=C2)C(C2=CC=C3)=O)=NC2=C3Cl)N=C1 FBAQLKQDLGQNHD-UHFFFAOYSA-N 0.000 description 1
- DSCTUPXADYWTEQ-UHFFFAOYSA-N NC1=NC(=C(C(=N1)NC(C)C1=NC2=CC=CC=C2C(N1C1=CC=CC=C1)=O)C#N)N Chemical compound NC1=NC(=C(C(=N1)NC(C)C1=NC2=CC=CC=C2C(N1C1=CC=CC=C1)=O)C#N)N DSCTUPXADYWTEQ-UHFFFAOYSA-N 0.000 description 1
- NHVLGNWTCHLWIV-ZDUSSCGKSA-N NC1=NC(=C(C(=N1)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl)C#N)C Chemical compound NC1=NC(=C(C(=N1)N[C@@H](C)C1=NC2=CC=CC(=C2C(N1C1=CC=CC=C1)=O)Cl)C#N)C NHVLGNWTCHLWIV-ZDUSSCGKSA-N 0.000 description 1
- NPCGIBPXBINPRO-UHFFFAOYSA-N O=C1N(C=NC2=CC=CC(=C12)C=1CCNCC1)C1=CC=CC=C1 Chemical compound O=C1N(C=NC2=CC=CC(=C12)C=1CCNCC1)C1=CC=CC=C1 NPCGIBPXBINPRO-UHFFFAOYSA-N 0.000 description 1
- NYXRNCOUPQGGED-UHFFFAOYSA-N O=C1N(C=NC2=CC=CC(=C12)OCC(N1CCCCC1)=O)C1=CC=CC=C1 Chemical compound O=C1N(C=NC2=CC=CC(=C12)OCC(N1CCCCC1)=O)C1=CC=CC=C1 NYXRNCOUPQGGED-UHFFFAOYSA-N 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 125000005415 substituted alkoxy group Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462016194P | 2014-06-24 | 2014-06-24 | |
| US62/016,194 | 2014-06-24 | ||
| PCT/US2015/037234 WO2015200352A1 (en) | 2014-06-24 | 2015-06-23 | Phosphatidylinositol 3-kinase inhibitors |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018051249A Division JP2018090644A (ja) | 2014-06-24 | 2018-03-19 | ホスファチジルイノシトール３−キナーゼ阻害剤 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2017519021A JP2017519021A (ja) | 2017-07-13 |
| JP2017519021A5 true JP2017519021A5 (OSRAM) | 2018-04-26 |
| JP6391718B2 JP6391718B2 (ja) | 2018-09-19 |
Family
ID=53674285
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016574424A Expired - Fee Related JP6391718B2 (ja) | 2014-06-24 | 2015-06-23 | ホスファチジルイノシトール３−キナーゼ阻害剤 |
| JP2018051249A Pending JP2018090644A (ja) | 2014-06-24 | 2018-03-19 | ホスファチジルイノシトール３−キナーゼ阻害剤 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018051249A Pending JP2018090644A (ja) | 2014-06-24 | 2018-03-19 | ホスファチジルイノシトール３−キナーゼ阻害剤 |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US9765060B2 (OSRAM) |
| EP (1) | EP3160960B1 (OSRAM) |
| JP (2) | JP6391718B2 (OSRAM) |
| KR (1) | KR20170015521A (OSRAM) |
| CN (1) | CN106459008A (OSRAM) |
| AR (1) | AR100975A1 (OSRAM) |
| AU (1) | AU2015280138B2 (OSRAM) |
| BR (1) | BR112016029846A2 (OSRAM) |
| CA (1) | CA2953820A1 (OSRAM) |
| EA (1) | EA201692487A1 (OSRAM) |
| ES (1) | ES2900812T3 (OSRAM) |
| HK (1) | HK1231474A1 (OSRAM) |
| IL (1) | IL249404A0 (OSRAM) |
| MA (1) | MA40045A (OSRAM) |
| MX (1) | MX2016017110A (OSRAM) |
| NZ (1) | NZ727185A (OSRAM) |
| SG (1) | SG11201610341PA (OSRAM) |
| TW (1) | TW201625558A (OSRAM) |
| WO (1) | WO2015200352A1 (OSRAM) |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20140213630A1 (en) | 2011-03-08 | 2014-07-31 | Thomas Diacovo | Methods and pharmaceutical compositions for treating lymphoid malignancy |
| EA201692266A1 (ru) | 2014-06-13 | 2017-06-30 | Джилид Сайэнс, Инк. | Ингибиторы фосфатидилинозитол-3-киназы |
| MX2016016530A (es) | 2014-06-13 | 2017-03-27 | Gilead Sciences Inc | Inhibidores de fosfatidilinositol 3-quinasa. |
| EA201692267A1 (ru) | 2014-06-13 | 2017-06-30 | Джилид Сайэнс, Инк. | Ингибиторы фосфатидилинозитол-3-киназы |
| HK1231477A1 (zh) | 2014-06-13 | 2017-12-22 | 吉利德科学公司 | 磷脂酰肌醇3-激酶抑制剂 |
| MA40250A (fr) | 2014-07-04 | 2017-05-10 | Lupin Ltd | Dérivés de quinolizinone utilisés comme inhibiteurs de pi3k |
| TWI808055B (zh) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Hdac 抑制劑與 pd-1 抑制劑之組合治療 |
| TWI794171B (zh) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Ｈｄａｃ抑制劑與ｐｄ-ｌ１抑制劑之組合治療 |
| TW201815787A (zh) * | 2016-09-23 | 2018-05-01 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201825465A (zh) | 2016-09-23 | 2018-07-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| TW201813963A (zh) | 2016-09-23 | 2018-04-16 | 美商基利科學股份有限公司 | 磷脂醯肌醇3-激酶抑制劑 |
| CN106632077B (zh) * | 2016-10-10 | 2019-01-22 | 上海再启生物技术有限公司 | 一种2-氨基-4-溴嘧啶的制备方法 |
| US10396145B2 (en) * | 2017-01-12 | 2019-08-27 | Micron Technology, Inc. | Memory cells comprising ferroelectric material and including current leakage paths having different total resistances |
| US20200165257A1 (en) * | 2017-06-22 | 2020-05-28 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Servic | Inhibitors of phosphoinositide 3-kinase and histone deacetylase for treatment of cancer |
| EP3661924A1 (en) * | 2017-07-31 | 2020-06-10 | The Trustees of Columbia University in the City of New York | Compounds, compositionals, and methods for treating t-cell acute lymphoblastic leukemia |
| AU2019209960B2 (en) | 2018-01-20 | 2023-11-23 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine compounds and methods of use |
| MX2021003576A (es) * | 2018-09-27 | 2021-05-28 | Shanghai Yingli Pharm Co Ltd | Forma cristalina de un compuesto de morfolino quinazolina, metodo de preparacion del mismo y uso del mismo. |
| US20220348558A1 (en) * | 2019-09-05 | 2022-11-03 | Wisconsin Alumni Research Foundation | Inhibitors of encephalitic alphaviruses |
| CN110590681B (zh) * | 2019-09-30 | 2021-06-01 | 中山大学 | 一种新型喹唑啉酮类化合物及其制备方法和应用 |
| WO2021086966A1 (en) * | 2019-10-29 | 2021-05-06 | Biogen Ma Inc. | Spirocyclic o-glycoprotein-2-acetamido-2-deoxy-3-d-glucopyranosidase inhibitors |
| CN113512042B (zh) * | 2020-04-09 | 2024-06-11 | 成都赜灵生物医药科技有限公司 | 取代喹唑啉-4-酮类化合物及其制备方法和用途 |
| WO2024064024A1 (en) * | 2022-09-19 | 2024-03-28 | Onkure, Inc. | ((4-oxo-3,4-dihydroquinazolin-8-yl)methyl)amine derivatives as p13k inhibitors for the treatment of cancer |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
| EP1278748B1 (en) | 2000-04-25 | 2011-03-23 | ICOS Corporation | Inhibitors of human phosphatidyl-inositol 3-kinase delta |
| US8193182B2 (en) * | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| DK2240451T3 (da) * | 2008-01-04 | 2017-11-20 | Intellikine Llc | Isoquinolinonderivater substitueret med en purin, der er anvendelig som pi3k-inhibitorer |
| AU2011255218B2 (en) | 2010-05-21 | 2015-03-12 | Infinity Pharmaceuticals, Inc. | Chemical compounds, compositions and methods for kinase modulation |
| AR091790A1 (es) * | 2011-08-29 | 2015-03-04 | Infinity Pharmaceuticals Inc | Derivados de isoquinolin-1-ona y sus usos |
| NZ708870A (en) * | 2012-12-21 | 2016-09-30 | Gilead Calistoga Llc | Isoquinolinone or quinazolinone phosphatidylinositol 3-kinase inhibitors |
| WO2014128612A1 (en) * | 2013-02-20 | 2014-08-28 | Novartis Ag | Quinazolin-4-one derivatives |
| UY35675A (es) * | 2013-07-24 | 2015-02-27 | Novartis Ag | Derivados sustituidos de quinazolin-4-ona |
| US20150148345A1 (en) * | 2013-11-26 | 2015-05-28 | Gilead Sciences, Inc. | Therapies for treating myeloproliferative disorders |
| WO2015168079A1 (en) | 2014-04-29 | 2015-11-05 | Infinity Pharmaceuticals, Inc. | Pyrimidine or pyridine derivatives useful as pi3k inhibitors |
| EA201692267A1 (ru) * | 2014-06-13 | 2017-06-30 | Джилид Сайэнс, Инк. | Ингибиторы фосфатидилинозитол-3-киназы |
| MX2016016530A (es) * | 2014-06-13 | 2017-03-27 | Gilead Sciences Inc | Inhibidores de fosfatidilinositol 3-quinasa. |
-
2015
- 2015-06-23 ES ES15739079T patent/ES2900812T3/es active Active
- 2015-06-23 EP EP15739079.0A patent/EP3160960B1/en active Active
- 2015-06-23 KR KR1020177001682A patent/KR20170015521A/ko not_active Abandoned
- 2015-06-23 MA MA040045A patent/MA40045A/fr unknown
- 2015-06-23 AR ARP150102013A patent/AR100975A1/es unknown
- 2015-06-23 SG SG11201610341PA patent/SG11201610341PA/en unknown
- 2015-06-23 CN CN201580034671.2A patent/CN106459008A/zh active Pending
- 2015-06-23 AU AU2015280138A patent/AU2015280138B2/en not_active Ceased
- 2015-06-23 MX MX2016017110A patent/MX2016017110A/es unknown
- 2015-06-23 CA CA2953820A patent/CA2953820A1/en not_active Abandoned
- 2015-06-23 JP JP2016574424A patent/JP6391718B2/ja not_active Expired - Fee Related
- 2015-06-23 EA EA201692487A patent/EA201692487A1/ru unknown
- 2015-06-23 BR BR112016029846A patent/BR112016029846A2/pt not_active IP Right Cessation
- 2015-06-23 HK HK17105165.9A patent/HK1231474A1/zh unknown
- 2015-06-23 WO PCT/US2015/037234 patent/WO2015200352A1/en not_active Ceased
- 2015-06-23 NZ NZ727185A patent/NZ727185A/en not_active IP Right Cessation
- 2015-06-23 US US14/747,931 patent/US9765060B2/en active Active
- 2015-06-24 TW TW104120373A patent/TW201625558A/zh unknown
-
2016
- 2016-12-06 IL IL249404A patent/IL249404A0/en unknown
-
2017
- 2017-08-17 US US15/680,045 patent/US20180065953A1/en not_active Abandoned
-
2018
- 2018-03-19 JP JP2018051249A patent/JP2018090644A/ja active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2017519021A5 (OSRAM) | ||
| JP7374960B2 (ja) | 縮合環化合物 | |
| KR101985050B1 (ko) | 피라진카르복사미드 화합물 | |
| JP5537704B2 (ja) | ２−（２，４，５−置換−アニリノ）ピリミジン化合物 | |
| KR102073854B1 (ko) | Egfr 돌연변이 키나아제 활성을 조절하기 위한 화합물 및 조성물 | |
| ES2677996T3 (es) | Nuevas indazolcarboxamidas, procedimiento para su preparación, preparaciones farmacéuticas que contienen las mismas, así como su uso para la preparación de medicamentos | |
| JP6097289B2 (ja) | セリン／スレオニンキナーゼインヒビターとしてのキナゾリン化合物 | |
| JP2018512381A5 (OSRAM) | ||
| MX2014012097A (es) | Compuesto heterociclico que contiene nitrogeno o sal del mismo. | |
| AU2015291478B2 (en) | Novel substituted pyrimidine compounds | |
| KR102111570B1 (ko) | 신규 이미다조피리다진 화합물 및 그의 용도 | |
| KR20160116033A (ko) | 2,4-이치환 페닐-1,5-디아민 유도체, 이의 응용, 및 이로 제조한 약물 조성물 | |
| JP2025519430A (ja) | 自己免疫疾患の処置のためのインダゾール大環状分子 | |
| JP2023522195A (ja) | 炎症性疾患の治療のための置換ピリジン | |
| RU2007130153A (ru) | Амидные производные | |
| JP2025540246A (ja) | Ｋｒａｓ ｇ１２ｄ阻害剤として新規な３環化合物およびその用途 | |
| JP2025540958A (ja) | 蕁麻疹の治療のための野生型ｃ－ｋｉｔキナーゼ阻害剤としてのＮ－フェニル－ピラゾロ［１，５－Ａ］ピリジン－３－カルボキサミド誘導体 | |
| JP2022505707A (ja) | 置換インドールおよびインダゾール化合物 | |
| WO2017005583A1 (en) | Triaza-spirodecanones as ddr1 inhibitors | |
| CN119325471A (zh) | Egfr抑制剂 | |
| TW201518290A (zh) | 作為傑納斯激酶（Ｊａｎｕｓ Ｋｉｎａｓｅ）抑制劑之新穎化合物 | |
| RU2783706C1 (ru) | Соединения с конденсированными кольцами | |
| KR20230061269A (ko) | 신규한 티에노[2,3-d]피리미딘 유도체, 이의 제조방법 및 이를 유효성분으로 포함하는 암 또는 자가면역질환의 예방 또는 치료용 약학적 조성물 | |
| HK40041215B (zh) | 稠环化合物 |