AU2010309832B2 - Compounds - Google Patents
Compounds Download PDFInfo
- Publication number
- AU2010309832B2 AU2010309832B2 AU2010309832A AU2010309832A AU2010309832B2 AU 2010309832 B2 AU2010309832 B2 AU 2010309832B2 AU 2010309832 A AU2010309832 A AU 2010309832A AU 2010309832 A AU2010309832 A AU 2010309832A AU 2010309832 B2 AU2010309832 B2 AU 2010309832B2
- Authority
- AU
- Australia
- Prior art keywords
- methyl
- amino
- pyrazolo
- pyrimidin
- hydroxyphenyl
- 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.)
- Ceased
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 233
- 238000000034 method Methods 0.000 claims abstract description 84
- 238000011282 treatment Methods 0.000 claims abstract description 37
- QMNUDYFKZYBWQX-UHFFFAOYSA-N 1H-quinazolin-4-one Chemical compound C1=CC=C2C(=O)N=CNC2=C1 QMNUDYFKZYBWQX-UHFFFAOYSA-N 0.000 claims description 208
- 125000000217 alkyl group Chemical group 0.000 claims description 200
- 229910052739 hydrogen Inorganic materials 0.000 claims description 192
- 239000001257 hydrogen Substances 0.000 claims description 74
- -1 C1- haloalkyl Chemical group 0.000 claims description 66
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 58
- 125000003118 aryl group Chemical group 0.000 claims description 47
- 229910052757 nitrogen Inorganic materials 0.000 claims description 47
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
- 125000000623 heterocyclic group Chemical group 0.000 claims description 39
- 125000005843 halogen group Chemical group 0.000 claims description 33
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 32
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 32
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 30
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 208000006673 asthma Diseases 0.000 claims description 22
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 22
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 21
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 150000002367 halogens Chemical class 0.000 claims description 20
- 230000005764 inhibitory process Effects 0.000 claims description 20
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 18
- 125000001188 haloalkyl group Chemical group 0.000 claims description 17
- DRXWSHCGSIJSID-UHFFFAOYSA-N hex-5-ynamide Chemical compound NC(=O)CCCC#C DRXWSHCGSIJSID-UHFFFAOYSA-N 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 150000002431 hydrogen Chemical group 0.000 claims description 14
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 13
- 230000000155 isotopic effect Effects 0.000 claims description 11
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 6
- 206010006458 Bronchitis chronic Diseases 0.000 claims description 6
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
- 201000004681 Psoriasis Diseases 0.000 claims description 6
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
- 201000010105 allergic rhinitis Diseases 0.000 claims description 6
- 201000008937 atopic dermatitis Diseases 0.000 claims description 6
- 206010006451 bronchitis Diseases 0.000 claims description 6
- 239000000969 carrier Substances 0.000 claims description 6
- 208000007451 chronic bronchitis Diseases 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 206010006187 Breast cancer Diseases 0.000 claims description 5
- 208000026310 Breast neoplasm Diseases 0.000 claims description 5
- 206010006895 Cachexia Diseases 0.000 claims description 5
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 5
- 206010010741 Conjunctivitis Diseases 0.000 claims description 5
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 5
- 201000003883 Cystic fibrosis Diseases 0.000 claims description 5
- 206010012434 Dermatitis allergic Diseases 0.000 claims description 5
- 206010012442 Dermatitis contact Diseases 0.000 claims description 5
- 206010014561 Emphysema Diseases 0.000 claims description 5
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 5
- 206010027476 Metastases Diseases 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
- 206010033645 Pancreatitis Diseases 0.000 claims description 5
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 5
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 5
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 5
- 208000010668 atopic eczema Diseases 0.000 claims description 5
- 201000008275 breast carcinoma Diseases 0.000 claims description 5
- 208000010247 contact dermatitis Diseases 0.000 claims description 5
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 5
- 206010017758 gastric cancer Diseases 0.000 claims description 5
- 208000010749 gastric carcinoma Diseases 0.000 claims description 5
- 230000012010 growth Effects 0.000 claims description 5
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 5
- 201000001441 melanoma Diseases 0.000 claims description 5
- 230000009401 metastasis Effects 0.000 claims description 5
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 206010039083 rhinitis Diseases 0.000 claims description 5
- 201000000306 sarcoidosis Diseases 0.000 claims description 5
- 201000009890 sinusitis Diseases 0.000 claims description 5
- 201000000498 stomach carcinoma Diseases 0.000 claims description 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 4
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- ZKWFSTHEYLJLEL-UHFFFAOYSA-N morpholine-4-carboxamide Chemical compound NC(=O)N1CCOCC1 ZKWFSTHEYLJLEL-UHFFFAOYSA-N 0.000 claims description 4
- GUOMZPPHSZMFRS-UHFFFAOYSA-N 2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-chlorophenyl)methyl]-5-ethynylquinazolin-4-one Chemical compound N1=C(C=2C=C(O)C=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#C)=C2C(=O)N1CC1=CC=CC=C1Cl GUOMZPPHSZMFRS-UHFFFAOYSA-N 0.000 claims description 3
- LZLZWYUFFAROFC-UHFFFAOYSA-N 2-[[4-amino-3-(4-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-chlorophenyl)methyl]-5-(6-morpholin-4-yl-6-oxohex-1-ynyl)quinazolin-4-one Chemical compound N1=C(C=2C=CC(O)=CC=2)C=2C(N)=NC=NC=2N1CC(N(C(=O)C1=2)CC=3C(=CC=CC=3)Cl)=NC1=CC=CC=2C#CCCCC(=O)N1CCOCC1 LZLZWYUFFAROFC-UHFFFAOYSA-N 0.000 claims description 3
- LIIITXBRSNDMNY-UHFFFAOYSA-N 3-[[2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-5-[3-[2-(2-hydroxyethoxy)ethoxy]prop-1-ynyl]-4-oxoquinazolin-3-yl]methyl]benzonitrile Chemical compound N1=C(C=2C=C(O)C=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#CCOCCOCCO)=C2C(=O)N1CC1=CC=CC(C#N)=C1 LIIITXBRSNDMNY-UHFFFAOYSA-N 0.000 claims description 3
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 claims description 3
- NLAFCFUVNPEKMI-UHFFFAOYSA-N 6-[2-[[4-amino-3-(4-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-chlorophenyl)methyl]-4-oxoquinazolin-5-yl]hex-5-ynoic acid Chemical compound N1=C(C=2C=CC(O)=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#CCCCC(O)=O)=C2C(=O)N1CC1=CC=CC=C1Cl NLAFCFUVNPEKMI-UHFFFAOYSA-N 0.000 claims description 3
- OFCPMJGTZUVUSM-UHFFFAOYSA-N 6-heptynoic acid Chemical compound OC(=O)CCCCC#C OFCPMJGTZUVUSM-UHFFFAOYSA-N 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- DNUSLLSECCYLAU-UHFFFAOYSA-N 2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-chlorophenyl)methyl]-5-(6-morpholin-4-yl-6-oxohex-1-ynyl)quinazolin-4-one Chemical compound N1=C(C=2C=C(O)C=CC=2)C=2C(N)=NC=NC=2N1CC(N(C(=O)C1=2)CC=3C(=CC=CC=3)Cl)=NC1=CC=CC=2C#CCCCC(=O)N1CCOCC1 DNUSLLSECCYLAU-UHFFFAOYSA-N 0.000 claims description 2
- CWQXXYJTVPJDGB-UHFFFAOYSA-N 2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-methyl-1,3-thiazol-4-yl)methyl]-5-(6-morpholin-4-yl-6-oxohex-1-ynyl)quinazolin-4-one Chemical compound S1C(C)=NC(CN2C(C3=C(C#CCCCC(=O)N4CCOCC4)C=CC=C3N=C2CN2C3=NC=NC(N)=C3C(C=3C=C(O)C=CC=3)=N2)=O)=C1 CWQXXYJTVPJDGB-UHFFFAOYSA-N 0.000 claims description 2
- ODGUATJPXSLVMA-UHFFFAOYSA-N 2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(3-chlorophenyl)methyl]-5-ethynylquinazolin-4-one Chemical compound N1=C(C=2C=C(O)C=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#C)=C2C(=O)N1CC1=CC=CC(Cl)=C1 ODGUATJPXSLVMA-UHFFFAOYSA-N 0.000 claims description 2
- DENSYDWNLNJEQR-UHFFFAOYSA-N 2-[[4-amino-3-(4-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-chlorophenyl)methyl]-5-ethynylquinazolin-4-one Chemical compound N1=C(C=2C=CC(O)=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#C)=C2C(=O)N1CC1=CC=CC=C1Cl DENSYDWNLNJEQR-UHFFFAOYSA-N 0.000 claims description 2
- DQQLMDLGTUARHB-UHFFFAOYSA-N 2-[[4-amino-3-(4-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-fluoro-3-methoxyphenyl)methyl]-5-(6-morpholin-4-yl-6-oxohex-1-ynyl)quinazolin-4-one Chemical compound COC1=CC=CC(CN2C(C3=C(C#CCCCC(=O)N4CCOCC4)C=CC=C3N=C2CN2C3=NC=NC(N)=C3C(C=3C=CC(O)=CC=3)=N2)=O)=C1F DQQLMDLGTUARHB-UHFFFAOYSA-N 0.000 claims description 2
- 125000004122 cyclic group Chemical group 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- XXUFRFNAQXDSQN-UHFFFAOYSA-N methyl 3-[[2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-5-(6-morpholin-4-yl-6-oxohex-1-ynyl)-4-oxoquinazolin-3-yl]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CN2C(C3=C(C#CCCCC(=O)N4CCOCC4)C=CC=C3N=C2CN2C3=NC=NC(N)=C3C(C=3C=C(O)C=CC=3)=N2)=O)=C1 XXUFRFNAQXDSQN-UHFFFAOYSA-N 0.000 claims description 2
- 125000003367 polycyclic group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 241000610375 Sparisoma viride Species 0.000 claims 6
- QWLHANNYZVBVDX-UHFFFAOYSA-N 2-ethynyl-3-[(3-methoxyphenyl)methyl]quinazolin-4-one Chemical compound C(#C)C1=NC2=CC=CC=C2C(N1CC1=CC(=CC=C1)OC)=O QWLHANNYZVBVDX-UHFFFAOYSA-N 0.000 claims 2
- IPGQKTUMRGDJGJ-UHFFFAOYSA-N 2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-chlorophenyl)methyl]-5-[3-(2-morpholin-4-ylethoxy)prop-1-ynyl]quinazolin-4-one Chemical compound N1=C(C=2C=C(O)C=CC=2)C=2C(N)=NC=NC=2N1CC(N(C(=O)C1=2)CC=3C(=CC=CC=3)Cl)=NC1=CC=CC=2C#CCOCCN1CCOCC1 IPGQKTUMRGDJGJ-UHFFFAOYSA-N 0.000 claims 1
- XHNPZUAUPCCLTH-UHFFFAOYSA-N 2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(2-chlorophenyl)methyl]-5-[3-[2-(2-methoxyethoxy)ethoxy]prop-1-ynyl]quinazolin-4-one Chemical compound C=1C=CC=C(Cl)C=1CN1C(=O)C=2C(C#CCOCCOCCOC)=CC=CC=2N=C1CN(C1=NC=NC(N)=C11)N=C1C1=CC=CC(O)=C1 XHNPZUAUPCCLTH-UHFFFAOYSA-N 0.000 claims 1
- KXTXIKMQFXXVEO-UHFFFAOYSA-N 2-[[4-amino-3-(3-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-5-ethynyl-3-[(2-fluorophenyl)methyl]quinazolin-4-one Chemical compound N1=C(C=2C=C(O)C=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#C)=C2C(=O)N1CC1=CC=CC=C1F KXTXIKMQFXXVEO-UHFFFAOYSA-N 0.000 claims 1
- ALEMKYQPUYKWDY-UHFFFAOYSA-N 2-[[4-amino-3-(4-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-3-[(3-chlorophenyl)methyl]-5-ethynylquinazolin-4-one Chemical compound N1=C(C=2C=CC(O)=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#C)=C2C(=O)N1CC1=CC=CC(Cl)=C1 ALEMKYQPUYKWDY-UHFFFAOYSA-N 0.000 claims 1
- JZGHEKRTCCGWQA-UHFFFAOYSA-N 2-[[4-amino-3-(4-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-5-ethynyl-3-[(2-fluorophenyl)methyl]quinazolin-4-one Chemical compound N1=C(C=2C=CC(O)=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#C)=C2C(=O)N1CC1=CC=CC=C1F JZGHEKRTCCGWQA-UHFFFAOYSA-N 0.000 claims 1
- HIWBXNVIXWHNRQ-UHFFFAOYSA-N 2-[[4-amino-3-(4-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]methyl]-5-ethynyl-3-[(4-fluorophenyl)methyl]quinazolin-4-one Chemical compound N1=C(C=2C=CC(O)=CC=2)C=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(C#C)=C2C(=O)N1CC1=CC=C(F)C=C1 HIWBXNVIXWHNRQ-UHFFFAOYSA-N 0.000 claims 1
- 102100025027 E3 ubiquitin-protein ligase TRIM69 Human genes 0.000 claims 1
- 101000830203 Homo sapiens E3 ubiquitin-protein ligase TRIM69 Proteins 0.000 claims 1
- 125000003282 alkyl amino group Chemical group 0.000 claims 1
- 125000005605 benzo group Chemical group 0.000 claims 1
- 125000006203 morpholinoethyl group Chemical group [H]C([H])(*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 54
- 208000027866 inflammatory disease Diseases 0.000 abstract description 5
- 230000000241 respiratory effect Effects 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 97
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 57
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000000543 intermediate Substances 0.000 description 45
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical group CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 37
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 35
- 239000000243 solution Substances 0.000 description 31
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 27
- 239000011541 reaction mixture Substances 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
- SRHBXINZKIKBKV-UHFFFAOYSA-N 3-[4-[tert-butyl(dimethyl)silyl]oxyphenyl]-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound C1=CC(O[Si](C)(C)C(C)(C)C)=CC=C1C1=NNC2=NC=NC(N)=C12 SRHBXINZKIKBKV-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 20
- 108091000080 Phosphotransferase Proteins 0.000 description 19
- 210000004027 cell Anatomy 0.000 description 19
- 102000020233 phosphotransferase Human genes 0.000 description 19
- GUSBTGLOEAEOHY-UHFFFAOYSA-N 3-[3-[tert-butyl(dimethyl)silyl]oxyphenyl]-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=CC(C=2C3=C(N)N=CN=C3NN=2)=C1 GUSBTGLOEAEOHY-UHFFFAOYSA-N 0.000 description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 210000004072 lung Anatomy 0.000 description 18
- 238000003818 flash chromatography Methods 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 238000009472 formulation Methods 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 239000002158 endotoxin Substances 0.000 description 13
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
- 229910052799 carbon Inorganic materials 0.000 description 11
- 229920006008 lipopolysaccharide Polymers 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 10
- QSZBEZQYDXTFAV-UHFFFAOYSA-N 1-morpholin-4-ylhex-5-yn-1-one Chemical compound C#CCCCC(=O)N1CCOCC1 QSZBEZQYDXTFAV-UHFFFAOYSA-N 0.000 description 10
- HQAIUXZORKJOJY-UHFFFAOYSA-N 3-iodo-2h-pyrazolo[3,4-d]pyrimidin-4-amine Chemical compound NC1=NC=NC2=NNC(I)=C12 HQAIUXZORKJOJY-UHFFFAOYSA-N 0.000 description 10
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 239000002953 phosphate buffered saline Substances 0.000 description 10
- 238000012360 testing method Methods 0.000 description 10
- BKFVFWRALOAYAW-UHFFFAOYSA-N 5-bromo-2-(chloromethyl)-3-[(2-chlorophenyl)methyl]quinazolin-4-one Chemical compound ClCC1=NC2=CC=CC(Br)=C2C(=O)N1CC1=CC=CC=C1Cl BKFVFWRALOAYAW-UHFFFAOYSA-N 0.000 description 9
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Classifications
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Landscapes
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| TW99135360 | 2010-10-18 | ||
| TW099135360A TWI478923B (zh) | 2009-10-19 | 2010-10-18 | 喹唑啉酮化合物及其用途 |
| PCT/EP2010/065746 WO2011048111A1 (en) | 2009-10-19 | 2010-10-19 | Compounds |
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| BRPI0821227A2 (pt) | 2007-12-19 | 2015-06-16 | Cancer Rec Tech Ltd | Composto, composição farmacêutica, método para preparar a mesma, uso de um composto, método para tratar uma doença ou distúrbio, para inibir função de raf e para inibir proliferação celular, inibir progressão do ciclo celular, promover apoptose, ou uma combinação de um ou mais dos mesmos |
| GB0918249D0 (en) | 2009-10-19 | 2009-12-02 | Respivert Ltd | Compounds |
| EP2531502B1 (en) | 2010-02-01 | 2014-04-02 | Cancer Research Technology Limited | 1-(5-tert-butyl-2-phenyl-2h-pyrazol-3-yl)-3-[2-fluoro-4-(1-methyl-2-oxo-2,3-dihydro-1h-imidazo[4,5-b]pyridin-7-yloxy)-phenyl]-urea and related compounds and their use in therapy |
| UY33337A (es) * | 2010-10-18 | 2011-10-31 | Respivert Ltd | DERIVADOS SUSTITUIDOS DE 1H-PIRAZOL[ 3,4-d]PIRIMIDINA COMO INHIBIDORES DE LAS FOSFOINOSITIDA 3-QUINASAS |
| CA2857302C (en) | 2011-12-15 | 2020-08-25 | Novartis Ag | Use of inhibitors of the activity or function of pi3k |
| KR20140131971A (ko) | 2012-03-13 | 2014-11-14 | 레스피버트 리미티드 | 신규 약학 제제 |
| US8940742B2 (en) | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CN104870017B (zh) | 2012-11-08 | 2020-08-14 | 理森制药股份公司 | 含有PDE4抑制剂和PI3δ或双重PI3δ-γ激酶抑制剂的药物组合物 |
| AR095353A1 (es) | 2013-03-15 | 2015-10-07 | Respivert Ltd | Compuesto |
| JO3279B1 (ar) | 2013-03-15 | 2018-09-16 | Respivert Ltd | مشتقات 2-((4- امينو -3- (3- فلورو-5- هيدروكسي فينيل)-h1- بيرازولو [d-3,4] بيرمدين-1-يل )ميثيل )- 3- (2- تراي فلورو ميثيل ) بينزيل ) كوينازولين -4 (h3)- واحد واستخدامها كمثبطات فوسفواينوسيتايد 3- كاينيز |
| EP3007711B1 (en) | 2013-06-14 | 2020-10-21 | Psioxus Therapeutics Limited | A dosing regime and formulations for type b adenoviruses |
| US9751888B2 (en) | 2013-10-04 | 2017-09-05 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| MX389256B (es) | 2013-10-04 | 2025-03-20 | Infinity Pharmaceuticals Inc | Compuestos heterociclicos y usos de los mismos. |
| GB201320732D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Methods of chemical synthesis |
| GB201320729D0 (en) | 2013-11-25 | 2014-01-08 | Cancer Rec Tech Ltd | Therapeutic compounds and their use |
| EA201691872A1 (ru) | 2014-03-19 | 2017-04-28 | Инфинити Фармасьютикалз, Инк. | Гетероциклические соединения для применения в лечении pi3k-гамма-опосредованных расстройств |
| GB201510197D0 (en) | 2014-06-12 | 2015-07-29 | Psioxus Therapeutics Ltd | Method of treating ovarian cancer |
| US9944639B2 (en) | 2014-07-04 | 2018-04-17 | Lupin Limited | Quinolizinone derivatives as PI3K inhibitors |
| WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| CN108349985A (zh) | 2015-09-14 | 2018-07-31 | 无限药品股份有限公司 | 异喹啉酮的固体形式、其制备方法、包含其的组合物及其使用方法 |
| WO2017161116A1 (en) | 2016-03-17 | 2017-09-21 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors |
| WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
| WO2019143874A1 (en) * | 2018-01-20 | 2019-07-25 | Sunshine Lake Pharma Co., Ltd. | Substituted aminopyrimidine compounds and methods of use |
| CN108516976B (zh) * | 2018-04-27 | 2020-07-03 | 四川大学华西医院 | 一种7-脱氮嘌呤衍生物及其四元环超分子结构 |
| WO2020058072A1 (en) * | 2018-09-18 | 2020-03-26 | Société des Produits Nestlé S.A. | Src inhibitor compounds for skeletal muscle modulation, methods and uses thereof |
| CN114258393B (zh) * | 2020-07-21 | 2024-11-22 | 中国医药研究开发中心有限公司 | 具有磷脂酰肌醇3-激酶δ和γ的双重抑制剂活性的杂环化合物及其医药用途 |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007114926A2 (en) * | 2006-04-04 | 2007-10-11 | The Regents Of The University Of California | Kinase antagonists |
Family Cites Families (53)
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| IT1204826B (it) | 1986-03-04 | 1989-03-10 | Chiesi Farma Spa | Composizioni farmaceutiche per inalazione |
| GB9501841D0 (en) | 1995-01-31 | 1995-03-22 | Co Ordinated Drug Dev | Improvements in and relating to carrier particles for use in dry powder inhalers |
| DK1131059T3 (da) | 1998-11-13 | 2003-06-30 | Jago Res Ag | Tørpulver til inhalation |
| DE1140938T1 (de) | 1999-01-11 | 2003-01-09 | Princeton University, Princeton | Kinase-inhibitoren mit hoher affinität zur ziel detektion und ihre verwendung |
| EP1158958B1 (en) | 1999-03-05 | 2007-06-06 | CHIESI FARMACEUTICI S.p.A. | Improved powdery pharmaceutical compositions for inhalation |
| PE20011227A1 (es) | 2000-04-17 | 2002-01-07 | Chiesi Farma Spa | Formulaciones farmaceuticas para inhaladores de polvo seco en la forma de aglomerados duros |
| US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
| KR100785363B1 (ko) | 2000-04-25 | 2007-12-18 | 이코스 코포레이션 | 인간 포스파티딜-이노시톨 3-키나제 델타의 억제제 |
| US6608053B2 (en) | 2000-04-27 | 2003-08-19 | Yamanouchi Pharmaceutical Co., Ltd. | Fused heteroaryl derivatives |
| CN1186324C (zh) | 2000-04-27 | 2005-01-26 | 山之内制药株式会社 | 稠合杂芳基衍生物 |
| EP1217000A1 (en) | 2000-12-23 | 2002-06-26 | Aventis Pharma Deutschland GmbH | Inhibitors of factor Xa and factor VIIa |
| JP2005509594A (ja) | 2001-07-13 | 2005-04-14 | バーチャル ドラッグ ディヴェロップメント、インコーポレイティッド | Ｎａｄシンテターゼ阻害剤およびその使用 |
| WO2003007955A2 (en) | 2001-07-20 | 2003-01-30 | Cancer Research Technology Limited | Biphenyl apurinic/apyrimidinic site endonuclease inhibitors to treat cancer |
| EP1553947A4 (en) | 2002-10-21 | 2006-11-29 | Bristol Myers Squibb Co | QUINAZOLINONES AND DERIVATIVES THEREOF AS FACTOR XA INHIBITORS |
| EP2385040A1 (en) | 2003-03-14 | 2011-11-09 | ONO Pharmaceutical Co., Ltd. | Nitrogen-containing heterocyclic derivatives and drugs containing the same as the active ingredient |
| US7122557B2 (en) | 2003-03-18 | 2006-10-17 | Bristol-Myers Squibb Company | Sulfonyl-amidino-containing and tetrahydropyrimidino-containing compounds as factor Xa inhibitors |
| WO2004089988A2 (en) | 2003-04-03 | 2004-10-21 | Protein Design Labs, Inc | Inhibitors of integrin alpha5beta1 and their use for the control of tissue granulation |
| US7429596B2 (en) | 2003-06-20 | 2008-09-30 | The Regents Of The University Of California | 1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof |
| GB0316341D0 (en) | 2003-07-11 | 2003-08-13 | Glaxo Group Ltd | Pharmaceutical formulations |
| WO2005012221A1 (ja) | 2003-08-04 | 2005-02-10 | Ono Pharmaceutical Co., Ltd. | ジフェニルエーテル化合物、その製造方法および用途 |
| WO2005016349A1 (en) | 2003-08-14 | 2005-02-24 | Icos Corporation | Methods of inhibiting leukocyte accumulation |
| WO2005016348A1 (en) | 2003-08-14 | 2005-02-24 | Icos Corporation | Method of inhibiting immune responses stimulated by an endogenous factor |
| GB0326632D0 (en) | 2003-11-14 | 2003-12-17 | Jagotec Ag | Dry powder formulations |
| CA2552664A1 (en) | 2004-01-08 | 2005-07-28 | Michigan State University | Methods for treating and preventing hypertension and hypertension-related disorders |
| WO2005113556A1 (en) * | 2004-05-13 | 2005-12-01 | Icos Corporation | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta |
| EP1750714A1 (en) | 2004-05-13 | 2007-02-14 | Vanderbilt University | Phosphoinositide 3-kinase delta selective inhibitors for inhibiting angiogenesis |
| JP2008500338A (ja) | 2004-05-25 | 2008-01-10 | イコス・コーポレイション | 造血細胞の異常増殖を治療及び／又は予防する方法 |
| CA2569406A1 (en) | 2004-06-04 | 2005-12-22 | Icos Corporation | Methods for treating mast cell disorders |
| WO2006030925A1 (ja) | 2004-09-13 | 2006-03-23 | Ono Pharmaceutical Co., Ltd. | 含窒素複素環誘導体およびそれらを有効成分とする薬剤 |
| GB0425758D0 (en) | 2004-11-23 | 2004-12-22 | Vectura Ltd | Preparation of pharmaceutical compositions |
| US20080287469A1 (en) | 2005-02-17 | 2008-11-20 | Diacovo Thomas G | Phosphoinositide 3-Kinase Inhibitors for Inhibiting Leukocyte Accumulation |
| GB0525254D0 (en) | 2005-12-12 | 2006-01-18 | Jagotec Ag | Powder compositions for inhalation |
| CN101448505A (zh) * | 2006-04-04 | 2009-06-03 | 加利福尼亚大学董事会 | Pi3激酶拮抗剂 |
| CN101495515A (zh) | 2006-05-24 | 2009-07-29 | 拜耳先灵医药股份有限公司 | 免疫原性降低的高亲和力人及人源化抗α5β1整联蛋白功能阻断性抗体 |
| EP2032560B1 (en) | 2006-06-29 | 2013-05-01 | Merck Sharp & Dohme Corp. | Substituted bicyclic and tricyclic thrombin receptor antagonists |
| GB0622818D0 (en) | 2006-11-15 | 2006-12-27 | Jagotec Ag | Improvements in or relating to organic compounds |
| US8362066B2 (en) | 2006-11-17 | 2013-01-29 | Treventis Corporation | Compounds and methods for treating protein folding disorders |
| US20090035306A1 (en) | 2006-11-29 | 2009-02-05 | Kalypsys, Inc. | Quinazolinone modulators of tgr5 |
| EP2137158A4 (en) | 2007-02-28 | 2012-04-18 | Methylgene Inc | LOW-MOLECULAR INHIBITORS OF PROTEINARGININE METHYLTRANSFERASES (PRMTS) |
| PE20090215A1 (es) * | 2007-05-09 | 2009-03-30 | Novartis Ag | Compuestos derivados de imidazopiridazinas como inhibidores de cinasa |
| WO2008140750A1 (en) | 2007-05-10 | 2008-11-20 | Hydra Biosciences Inc. | Compounds for modulating trpv3 function |
| MX358640B (es) | 2008-01-04 | 2018-08-29 | Intellikine Llc | Isoquinolin-1 (2h) -onas y tieno [2,3-d]pirimidin-4(3h) -onas substituidas, y metodos de uso de las mismas. |
| US8703778B2 (en) * | 2008-09-26 | 2014-04-22 | Intellikine Llc | Heterocyclic kinase inhibitors |
| WO2010059593A1 (en) | 2008-11-18 | 2010-05-27 | Intellikine, Inc. | Methods and compositions for treatment of ophthalmic conditions |
| CA2745280A1 (en) | 2008-12-04 | 2010-06-10 | The United States Of America, As Represented By The Secretary, Departmen T Of Health And Human Services | Phosphatidylinositol-3-kinase p110 delta-targeted drugs in the treatment of cns disorders |
| EP2379505A4 (en) | 2008-12-05 | 2012-10-17 | Designmedix Inc | CHLOROQUINES MODIFIED BY A MONOCYCLIC GROUP OR A FUSED CYCLE GROUP |
| US20110135655A1 (en) * | 2009-01-13 | 2011-06-09 | PHILADELPHIA HEALTH AND EDUCATION CORPORATION d/b/a Drexel University College of Medicine; | Role of PI3K p110 delta Signaling in Retroviral Infection and Replication |
| BRPI1012333A2 (pt) * | 2009-03-24 | 2016-03-29 | Gilead Calistoga Llc | atropisômeros de derivados de 2-purinil-3-tolil-quinazolinonas e métodos de uso |
| WO2011015037A1 (en) | 2009-08-05 | 2011-02-10 | The University Of Hongkong | Antiviral compounds and methods of making and using there of cross reference to related applications |
| GB0918249D0 (en) | 2009-10-19 | 2009-12-02 | Respivert Ltd | Compounds |
| CA2813096C (en) | 2010-09-30 | 2019-10-29 | Chiesi Farmaceutici S.P.A. | Use of magnesium stearate in dry powder formulations for inhalation |
| UY33337A (es) * | 2010-10-18 | 2011-10-31 | Respivert Ltd | DERIVADOS SUSTITUIDOS DE 1H-PIRAZOL[ 3,4-d]PIRIMIDINA COMO INHIBIDORES DE LAS FOSFOINOSITIDA 3-QUINASAS |
| KR20140131971A (ko) | 2012-03-13 | 2014-11-14 | 레스피버트 리미티드 | 신규 약학 제제 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007114926A2 (en) * | 2006-04-04 | 2007-10-11 | The Regents Of The University Of California | Kinase antagonists |
| WO2008127226A2 (en) * | 2006-04-04 | 2008-10-23 | The Regents Of The University Of California | P13 kinase antagonists |
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