JP2017519021A5 - - Google Patents
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- 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
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- -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
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| US20220348558A1 (en) * | 2019-09-05 | 2022-11-03 | Wisconsin Alumni Research Foundation | Inhibitors of encephalitic alphaviruses |
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| US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 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 |
| EP2571357B1 (en) * | 2010-05-21 | 2016-07-06 | 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 |
| EP2935246B1 (en) * | 2012-12-21 | 2018-07-25 | 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 |
| AU2014354769A1 (en) * | 2013-11-26 | 2016-05-26 | 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 |
| CA2952025A1 (en) * | 2014-06-13 | 2015-12-17 | Gilead Sciences, Inc. | Phosphatidylinositol 3-kinase inhibitors |
| JP6455995B2 (ja) * | 2014-06-13 | 2019-01-23 | ギリアード サイエンシーズ， インコーポレイテッド | ホスファチジルイノシトール３−キナーゼ阻害剤 |
-
2015
- 2015-06-23 KR KR1020177001682A patent/KR20170015521A/ko not_active Abandoned
- 2015-06-23 CA CA2953820A patent/CA2953820A1/en not_active Abandoned
- 2015-06-23 SG SG11201610341PA patent/SG11201610341PA/en unknown
- 2015-06-23 NZ NZ727185A patent/NZ727185A/en not_active IP Right Cessation
- 2015-06-23 JP JP2016574424A patent/JP6391718B2/ja not_active Expired - Fee Related
- 2015-06-23 MA MA040045A patent/MA40045A/fr unknown
- 2015-06-23 AU AU2015280138A patent/AU2015280138B2/en not_active Ceased
- 2015-06-23 EA EA201692487A patent/EA201692487A1/ru unknown
- 2015-06-23 ES ES15739079T patent/ES2900812T3/es active Active
- 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 US US14/747,931 patent/US9765060B2/en active Active
- 2015-06-23 CN CN201580034671.2A patent/CN106459008A/zh active Pending
- 2015-06-23 AR ARP150102013A patent/AR100975A1/es unknown
- 2015-06-23 MX MX2016017110A patent/MX2016017110A/es unknown
- 2015-06-23 EP EP15739079.0A patent/EP3160960B1/en active Active
- 2015-06-23 WO PCT/US2015/037234 patent/WO2015200352A1/en not_active Ceased
- 2015-06-24 TW TW104120373A patent/TW201625558A/zh unknown
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2016
- 2016-12-06 IL IL249404A patent/IL249404A0/en unknown
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2017
- 2017-08-17 US US15/680,045 patent/US20180065953A1/en not_active Abandoned
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2018
- 2018-03-19 JP JP2018051249A patent/JP2018090644A/ja active Pending
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