HRP20020838A2 - Inhibitors of human phosphatidyl-inositol 3-kinase delta - Google Patents

Inhibitors of human phosphatidyl-inositol 3-kinase delta Download PDF

Info

Publication number: HRP20020838A2
Authority: HR; Croatia
Prior art keywords: quinazolin; purin; ylsulfanylmethyl; methyl; chlorophenyl
Prior art date: 2000-04-25

Application number

Other languages

English (en)

Croatian (hr)

Inventor

Chanchal Sadhu

Ken Dick

Jennifer Treiberg

C Gregory Sowell

Edward A Kesicki

Amy Oliver

Original Assignee

Icos Corp

Priority date (The priority date 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 date listed.)

2000-04-25

Filing date

2002-10-21

Publication date

2004-12-31

2002-10-21 Application filed by Icos Corp filed Critical Icos Corp

2004-12-31 Publication of HRP20020838A2 publication Critical patent/HRP20020838A2/hr

2012-12-31 Publication of HRP20020838B1 publication Critical patent/HRP20020838B1/xx

Links

108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 title claims abstract description 83
108091007960 PI3Ks Proteins 0.000 title claims abstract description 71
239000003112 inhibitor Substances 0.000 title description 73
102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 title description 33
150000001875 compounds Chemical class 0.000 claims abstract description 305
238000000034 method Methods 0.000 claims abstract description 258
230000000694 effects Effects 0.000 claims abstract description 154
102000038030 PI3Ks Human genes 0.000 claims abstract description 70
230000002401 inhibitory effect Effects 0.000 claims abstract description 58
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 55
210000000265 leukocyte Anatomy 0.000 claims abstract description 44
108010029485 Protein Isoforms Proteins 0.000 claims abstract description 41
102000001708 Protein Isoforms Human genes 0.000 claims abstract description 41
208000035475 disorder Diseases 0.000 claims abstract description 25
210000004027 cell Anatomy 0.000 claims description 102
210000000440 neutrophil Anatomy 0.000 claims description 86
239000000460 chlorine Substances 0.000 claims description 82
-1 4-methylpiperazinyl Chemical group 0.000 claims description 54
125000003118 aryl group Chemical group 0.000 claims description 54
229910052739 hydrogen Inorganic materials 0.000 claims description 46
108090000765 processed proteins & peptides Proteins 0.000 claims description 46
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
102000004196 processed proteins & peptides Human genes 0.000 claims description 42
239000001257 hydrogen Substances 0.000 claims description 40
229910052736 halogen Inorganic materials 0.000 claims description 38
210000003719 b-lymphocyte Anatomy 0.000 claims description 37
150000002367 halogens Chemical class 0.000 claims description 37
229920001184 polypeptide Polymers 0.000 claims description 37
238000004458 analytical method Methods 0.000 claims description 35
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 34
125000001072 heteroaryl group Chemical group 0.000 claims description 32
230000005764 inhibitory process Effects 0.000 claims description 31
OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 claims description 30
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 27
125000000217 alkyl group Chemical group 0.000 claims description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 24
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims description 24
241001465754 Metazoa Species 0.000 claims description 24
229910052760 oxygen Inorganic materials 0.000 claims description 23
210000002997 osteoclast Anatomy 0.000 claims description 22
229910052757 nitrogen Inorganic materials 0.000 claims description 21
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
230000005012 migration Effects 0.000 claims description 20
238000013508 migration Methods 0.000 claims description 20
159000000021 acetate salts Chemical class 0.000 claims description 19
230000028023 exocytosis Effects 0.000 claims description 19
125000005842 heteroatom Chemical group 0.000 claims description 19
229910052717 sulfur Inorganic materials 0.000 claims description 19
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 18
GNWHRHGTIBRNSM-UHFFFAOYSA-N IC-87114 Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 GNWHRHGTIBRNSM-UHFFFAOYSA-N 0.000 claims description 17
230000006378 damage Effects 0.000 claims description 17
230000035755 proliferation Effects 0.000 claims description 17
210000003651 basophil Anatomy 0.000 claims description 16
210000001744 T-lymphocyte Anatomy 0.000 claims description 15
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 14
229910052799 carbon Inorganic materials 0.000 claims description 14
125000004122 cyclic group Chemical group 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
241000894006 Bacteria Species 0.000 claims description 12
229960001340 histamine Drugs 0.000 claims description 12
125000002950 monocyclic group Chemical group 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 12
HTIJYCXXPTXUPT-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-methyl-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1Cl HTIJYCXXPTXUPT-UHFFFAOYSA-N 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 11
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 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
229910052801 chlorine Inorganic materials 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 10
239000001301 oxygen Substances 0.000 claims description 10
239000012453 solvate Substances 0.000 claims description 10
GQRNGAVFBOEJOE-UHFFFAOYSA-N 2-(7h-purin-6-ylsulfanylmethyl)-3-pyridin-4-ylquinazolin-4-one Chemical compound N=1C=NC=2NC=NC=2C=1SCC1=NC2=CC=CC=C2C(=O)N1C1=CC=NC=C1 GQRNGAVFBOEJOE-UHFFFAOYSA-N 0.000 claims description 9
XIIBYVZCAGZAPQ-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chlorophenyl)-5-fluoroquinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(F)=C2C(=O)N1C1=CC=CC=C1Cl XIIBYVZCAGZAPQ-UHFFFAOYSA-N 0.000 claims description 9
XBBAOYPWNSDSCP-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-fluorophenyl)-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1=CC=CC=C1F XBBAOYPWNSDSCP-UHFFFAOYSA-N 0.000 claims description 9
RXTIEVBLHKGDBF-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-benzyl-5-fluoroquinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(F)=C2C(=O)N1CC1=CC=CC=C1 RXTIEVBLHKGDBF-UHFFFAOYSA-N 0.000 claims description 9
MQGUQBFVGGNFBF-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-fluorophenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1F MQGUQBFVGGNFBF-UHFFFAOYSA-N 0.000 claims description 9
XWHYLSLNUHYGHD-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-methyl-3-(2-propan-2-ylphenyl)quinazolin-4-one Chemical compound CC(C)C1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 XWHYLSLNUHYGHD-UHFFFAOYSA-N 0.000 claims description 9
PRNXFEYDFGYIMH-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-8-chloro-3-(2-chlorophenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=C(Cl)C=CC=C2C(=O)N1C1=CC=CC=C1Cl PRNXFEYDFGYIMH-UHFFFAOYSA-N 0.000 claims description 9
MBGJAPVUBQHSDQ-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-5-methyl-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=C(Cl)C=CC=C1Cl MBGJAPVUBQHSDQ-UHFFFAOYSA-N 0.000 claims description 9
PXULODRRUGHRFJ-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-fluoro-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C=2C(F)=CC=CC=2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1Cl PXULODRRUGHRFJ-UHFFFAOYSA-N 0.000 claims description 9
TUUZKUKCKBFCKN-UHFFFAOYSA-N 3-(2-chlorophenyl)-7-fluoro-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound C=1C(F)=CC=C(C2=O)C=1N=C(CSC=1C=3N=CNC=3N=CN=1)N2C1=CC=CC=C1Cl TUUZKUKCKBFCKN-UHFFFAOYSA-N 0.000 claims description 9
CPFAYZNWSBKNPD-UHFFFAOYSA-N 3-(2-fluorophenyl)-5-methyl-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1F CPFAYZNWSBKNPD-UHFFFAOYSA-N 0.000 claims description 9
LCJUFANUVMUYHE-UHFFFAOYSA-N 3-(2-methoxyphenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound COC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1CSC1=NC=NC2=C1N=CN2 LCJUFANUVMUYHE-UHFFFAOYSA-N 0.000 claims description 9
VFMDKLUBYRSGRJ-UHFFFAOYSA-N 3-(3-chlorophenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound ClC1=CC=CC(N2C(C3=CC=CC=C3N=C2CSC=2C=3N=CNC=3N=CN=2)=O)=C1 VFMDKLUBYRSGRJ-UHFFFAOYSA-N 0.000 claims description 9
LUMJAEYXABJACN-UHFFFAOYSA-N 3-benzyl-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound N=1C=NC=2NC=NC=2C=1SCC1=NC2=CC=CC=C2C(=O)N1CC1=CC=CC=C1 LUMJAEYXABJACN-UHFFFAOYSA-N 0.000 claims description 9
VIELATKZAHIKMR-UHFFFAOYSA-N 3-butyl-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound C1=CC=C2C(=O)N(CCCC)C(CSC=3C=4N=CNC=4N=CN=3)=NC2=C1 VIELATKZAHIKMR-UHFFFAOYSA-N 0.000 claims description 9
NTOXKILKZRKVHC-UHFFFAOYSA-N 5-chloro-3-(2-chlorophenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound ClC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CSC1=NC=NC2=C1N=CN2 NTOXKILKZRKVHC-UHFFFAOYSA-N 0.000 claims description 9
VDOLSOHFRBGGER-UHFFFAOYSA-N 5-chloro-3-(2-phenylphenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C=2C(Cl)=CC=CC=2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1C1=CC=CC=C1 VDOLSOHFRBGGER-UHFFFAOYSA-N 0.000 claims description 9
FOKJPGMZFLETIP-UHFFFAOYSA-N 6-chloro-3-(2-chlorophenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C2=CC(Cl)=CC=C2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1Cl FOKJPGMZFLETIP-UHFFFAOYSA-N 0.000 claims description 9
HPLXTIBGXSKSAR-UHFFFAOYSA-N 8-chloro-3-(2-chlorophenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound ClC1=CC=CC=C1N1C(=O)C2=CC=CC(Cl)=C2N=C1CSC1=NC=NC2=C1N=CN2 HPLXTIBGXSKSAR-UHFFFAOYSA-N 0.000 claims description 9
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
125000005037 alkyl phenyl group Chemical group 0.000 claims description 9
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
239000004305 biphenyl Chemical group 0.000 claims description 9
235000010290 biphenyl Nutrition 0.000 claims description 9
230000001413 cellular effect Effects 0.000 claims description 9
YZLYMDXNNPAUOE-UHFFFAOYSA-N ethyl 2-[5-fluoro-4-oxo-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-3-yl]acetate Chemical compound C1=CC(F)=C2C(=O)N(CC(=O)OCC)C(CSC=3C=4N=CNC=4N=CN=3)=NC2=C1 YZLYMDXNNPAUOE-UHFFFAOYSA-N 0.000 claims description 9
125000005059 halophenyl group Chemical group 0.000 claims description 9
125000002757 morpholinyl group Chemical group 0.000 claims description 9
239000011593 sulfur Chemical group 0.000 claims description 9
VRZOWGGKIACNIC-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chlorophenyl)-5-methylquinazolin-4-one Chemical compound O=C1C=2C(C)=CC=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1=CC=CC=C1Cl VRZOWGGKIACNIC-UHFFFAOYSA-N 0.000 claims description 8
GMDVVVIIGZYKOU-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-butylquinazolin-4-one Chemical compound C1=CC=C2C(=O)N(CCCC)C(CN3C4=NC=NC(N)=C4N=C3)=NC2=C1 GMDVVVIIGZYKOU-UHFFFAOYSA-N 0.000 claims description 8
IBIHUDVRLLQWNN-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-morpholin-4-ylquinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC=C2C(=O)N1N1CCOCC1 IBIHUDVRLLQWNN-UHFFFAOYSA-N 0.000 claims description 8
JDGRYIPYEMCXIZ-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-chlorophenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1Cl JDGRYIPYEMCXIZ-UHFFFAOYSA-N 0.000 claims description 8
HKGGEZVQRAZEDJ-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-methylphenyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 HKGGEZVQRAZEDJ-UHFFFAOYSA-N 0.000 claims description 8
LVMDQSBZDBGLET-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-phenylphenyl)quinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC=CC(Cl)=C2C(=O)N1C1=CC=CC=C1C1=CC=CC=C1 LVMDQSBZDBGLET-UHFFFAOYSA-N 0.000 claims description 8
FACKVRVYNBIHKR-UHFFFAOYSA-N 3-(2-chlorophenyl)-6,7-difluoro-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C=2C=C(F)C(F)=CC=2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1Cl FACKVRVYNBIHKR-UHFFFAOYSA-N 0.000 claims description 8
HJQDJCZJGUJVAL-UHFFFAOYSA-N 3-(2-chlorophenyl)-6-fluoro-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C2=CC(F)=CC=C2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1Cl HJQDJCZJGUJVAL-UHFFFAOYSA-N 0.000 claims description 8
LJXQHSIWGJFSPF-UHFFFAOYSA-N 3-(2-chlorophenyl)-6-hydroxy-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C2=CC(O)=CC=C2N=C(CSC=2C=3N=CNC=3N=CN=2)N1C1=CC=CC=C1Cl LJXQHSIWGJFSPF-UHFFFAOYSA-N 0.000 claims description 8
RRLQCEWOZZHPEX-UHFFFAOYSA-N 3-benzyl-5-fluoro-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound O=C1C=2C(F)=CC=CC=2N=C(CSC=2C=3N=CNC=3N=CN=2)N1CC1=CC=CC=C1 RRLQCEWOZZHPEX-UHFFFAOYSA-N 0.000 claims description 8
SQMPUCYQFAPBHU-UHFFFAOYSA-N 3-morpholin-4-yl-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound N=1C=NC=2NC=NC=2C=1SCC1=NC2=CC=CC=C2C(=O)N1N1CCOCC1 SQMPUCYQFAPBHU-UHFFFAOYSA-N 0.000 claims description 8
WYJOTPRHMODJAI-UHFFFAOYSA-N 5-chloro-3-(2-fluorophenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound FC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CSC1=NC=NC2=C1N=CN2 WYJOTPRHMODJAI-UHFFFAOYSA-N 0.000 claims description 8
ULJHRLXEOKBUDN-UHFFFAOYSA-N 5-chloro-3-(2-methylphenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound CC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CSC1=NC=NC2=C1N=CN2 ULJHRLXEOKBUDN-UHFFFAOYSA-N 0.000 claims description 8
DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 8
230000001580 bacterial effect Effects 0.000 claims description 8
230000003399 chemotactic effect Effects 0.000 claims description 8
230000012010 growth Effects 0.000 claims description 8
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125000004430 oxygen atom Chemical group O* 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
125000004434 sulfur atom Chemical group 0.000 claims description 8
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
CVLAPCOXQCXBJO-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chlorophenyl)-7-fluoroquinazolin-4-one Chemical compound C1=NC=2C(N)=NC=NC=2N1CC1=NC2=CC(F)=CC=C2C(=O)N1C1=CC=CC=C1Cl CVLAPCOXQCXBJO-UHFFFAOYSA-N 0.000 claims description 7
PKBPNAZXEHHSPC-UHFFFAOYSA-N 3-(4-methylpiperazin-1-yl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound C1CN(C)CCN1N1C(=O)C2=CC=CC=C2N=C1CSC1=NC=NC2=C1N=CN2 PKBPNAZXEHHSPC-UHFFFAOYSA-N 0.000 claims description 7
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 7
125000002947 alkylene group Chemical group 0.000 claims description 7
229910052731 fluorine Inorganic materials 0.000 claims description 7
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 7
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
UMMYTDJYDSTEMB-UHFFFAOYSA-N 2-((9h-purin-6-ylthio)methyl)-5-chloro-3-(2-methoxyphenyl)quinazolin-4(3h)-one Chemical compound COC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CSC1=NC=NC2=C1N=CN2 UMMYTDJYDSTEMB-UHFFFAOYSA-N 0.000 claims description 6
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 6
VVLWHQXECGWDMR-UHFFFAOYSA-N 5-methyl-3-(2-propan-2-ylphenyl)-2-(7h-purin-6-ylsulfanylmethyl)quinazolin-4-one Chemical compound CC(C)C1=CC=CC=C1N1C(=O)C2=C(C)C=CC=C2N=C1CSC1=NC=NC2=C1N=CN2 VVLWHQXECGWDMR-UHFFFAOYSA-N 0.000 claims description 6
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
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MPVDXIMFBOLMNW-UHFFFAOYSA-N chembl1615565 Chemical compound OC1=CC=C2C=C(S(O)(=O)=O)C=C(S(O)(=O)=O)C2=C1N=NC1=CC=CC=C1 MPVDXIMFBOLMNW-UHFFFAOYSA-N 0.000 claims description 6
101150068479 chrb gene Proteins 0.000 claims description 6
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 6
230000008782 phagocytosis Effects 0.000 claims description 6
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 6
VVRQFRVUVPOQPU-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-3-(2-chlorophenyl)-6,7-dimethoxyquinazolin-4-one Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2N=C(CN2C3=NC=NC(N)=C3N=C2)N1C1=CC=CC=C1Cl VVRQFRVUVPOQPU-UHFFFAOYSA-N 0.000 claims description 5
IOOGLFCOTPZWOV-UHFFFAOYSA-N 2-[(6-aminopurin-9-yl)methyl]-5-chloro-3-(2-methoxyphenyl)quinazolin-4-one Chemical compound COC1=CC=CC=C1N1C(=O)C2=C(Cl)C=CC=C2N=C1CN1C2=NC=NC(N)=C2N=C1 IOOGLFCOTPZWOV-UHFFFAOYSA-N 0.000 claims description 5
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Classifications

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HRP20020838 2000-04-25 2002-10-21 Inhibitors of human phosphatidyl-inositol 3-kinase delta HRP20020838A2 (en)

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US19965500P	2000-04-25	2000-04-25
US23805700P	2000-10-05	2000-10-05
PCT/US2001/013315 WO2001081346A2 (en)	2000-04-25	2001-04-24	Inhibitors of human phosphatidyl-inositol 3-kinase delta

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HRP20020838A2 true HRP20020838A2 (en)	2004-12-31
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JP2003531209A (ja)	2003-10-21
EA200200990A1 (ru)	2003-06-26
ES2788383T3 (es)	2020-10-21
KR20020093077A (ko)	2002-12-12
EP3029041B1 (en)	2020-03-04
HUP0300497A3 (en)	2004-10-28
EA008241B1 (ru)	2007-04-27
WO2001081346A3 (en)	2002-03-21
EP2223922A3 (en)	2011-04-27
ATE502941T1 (de)	2011-04-15
NO20100777L (no)	2002-12-10
NO20025104L (no)	2002-12-10
ES2527754T3 (es)	2015-01-29
MXPA02010618A (es)	2004-05-05
US20030195211A1 (en)	2003-10-16
PT3029041T (pt)	2020-05-13
IS6585A (is)	2002-10-21
HRP20020838B1 (es)	2012-12-31
BR0110371A (pt)	2003-06-17
SI3029041T1 (sl)	2020-08-31
IL152275A0 (en)	2003-05-29
HU230554B1 (hu)	2016-12-28
IL245146A0 (en)	2016-06-30
NO20025104D0 (no)	2002-10-24
SI2223922T1 (sl)	2016-04-29
PT1939203E (pt)	2015-02-04
YU80402A (sh)	2005-09-19
US6518277B1 (en)	2003-02-11
CN1440408B (zh)	2012-07-18
CA2406278C (en)	2012-06-05
EP1278748B1 (en)	2011-03-23
DK2223922T3 (en)	2016-06-06
NO329136B1 (no)	2010-08-30
HUP0300497A2 (hu)	2003-06-28
EP1278748A2 (en)	2003-01-29
PT1278748E (pt)	2011-03-31
BRPI0110371B8 (pt)	2021-05-25
IS2822B (is)	2013-02-15
JP4642309B2 (ja)	2011-03-02
CN1440408A (zh)	2003-09-03
DK1278748T3 (da)	2011-04-18
DK1939203T3 (en)	2015-02-23
EP2223922B1 (en)	2016-03-02
AU2001255667C1 (en)	2016-06-09
ES2567260T3 (es)	2016-04-21
IL231360A (en)	2016-04-21
HK1053308A1 (en)	2003-10-17
AU5566701A (en)	2001-11-07
EP2223922A2 (en)	2010-09-01
US6800620B2 (en)	2004-10-05
BRPI0110371B1 (pt)	2016-09-27
RS51458B (sr)	2011-04-30
WO2001081346A2 (en)	2001-11-01
CY1117672T1 (el)	2017-05-17
IL231360A0 (en)	2014-04-30
NZ522076A (en)	2005-08-26
DE60144277D1 (de)	2011-05-05
EP3029041A1 (en)	2016-06-08
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Publication	Publication Date	Title
US10695349B2 (en)	2020-06-30	Inhibitors of human phosphatidylinositol 3-kinase delta
HRP20020838A2 (en)	2004-12-31	Inhibitors of human phosphatidyl-inositol 3-kinase delta
AU2002323426A1 (en)	2003-07-03	Inhibitors of human phosphatidyl-inositol 3-kinase delta
AU2001255667A1 (en)	2002-01-24	Inhibitors of human phosphatidyl-inositol 3-kinase delta
EP1939203A2 (en)	2008-07-02	Inhibitors of human phosphatidyl-inositol 3-kinase delta isoform
PL213200B1 (pl)	2013-01-31	Selektywne inhibitory PI3Kδ, kompozycje je zawierajace oraz ich zastosowania medyczne

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