NO328890B1 - Pyrrolopyrimidiner, anvendelse derav og farmasoytisk sammensetning omfattende en slik forbindelse - Google Patents

Pyrrolopyrimidiner, anvendelse derav og farmasoytisk sammensetning omfattende en slik forbindelse Download PDF

Info

Publication number: NO328890B1
Authority: NO; Norway
Prior art keywords: dimethyl; propyl; carbonitrile; pyrrolo; pyrimidine
Prior art date: 2001-08-30

Application number

NO20041180A

Other languages

English (en)

Norwegian (no)

Other versions

NO20041180L (no

Inventor

Martin Missbach

Naoki Teno

Kenji Hayakawa

Genji Iwasaki

Claudia Betschart

Osamu Irie

Junichi Sakaki

Rene Lattmann

Original Assignee

Novartis Ag

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.)

2001-08-30

Filing date

2004-03-19

Publication date

2010-06-07

2004-03-19 Application filed by Novartis Ag filed Critical Novartis Ag

2004-03-19 Publication of NO20041180L publication Critical patent/NO20041180L/no

2010-06-07 Publication of NO328890B1 publication Critical patent/NO328890B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 193
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
150000004944 pyrrolopyrimidines Chemical class 0.000 title description 2
-1 carboxy, formyl Chemical group 0.000 claims description 265
IIHQNAXFIODVDU-UHFFFAOYSA-N pyrimidine-2-carbonitrile Chemical compound N#CC1=NC=CC=N1 IIHQNAXFIODVDU-UHFFFAOYSA-N 0.000 claims description 78
125000000217 alkyl group Chemical group 0.000 claims description 74
LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 claims description 45
125000003118 aryl group Chemical group 0.000 claims description 37
125000003545 alkoxy group Chemical group 0.000 claims description 29
229910052736 halogen Inorganic materials 0.000 claims description 27
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
150000002367 halogens Chemical class 0.000 claims description 25
238000002360 preparation method Methods 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 22
229920006395 saturated elastomer Polymers 0.000 claims description 21
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
125000001424 substituent group Chemical group 0.000 claims description 19
125000005843 halogen group Chemical group 0.000 claims description 17
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
102000004171 Cathepsin K Human genes 0.000 claims description 16
108090000625 Cathepsin K Proteins 0.000 claims description 16
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
201000010099 disease Diseases 0.000 claims description 14
125000000753 cycloalkyl group Chemical group 0.000 claims description 13
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
229910020008 S(O) Inorganic materials 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 12
125000000623 heterocyclic group Chemical group 0.000 claims description 12
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 12
125000004093 cyano group Chemical group *C#N 0.000 claims description 11
125000004104 aryloxy group Chemical group 0.000 claims description 10
125000004043 oxo group Chemical group O=* 0.000 claims description 10
125000003435 aroyl group Chemical group 0.000 claims description 9
150000002148 esters Chemical class 0.000 claims description 9
CYJAWBVQRMVFEO-UHFFFAOYSA-N piperazine-2,6-dione Chemical compound O=C1CNCC(=O)N1 CYJAWBVQRMVFEO-UHFFFAOYSA-N 0.000 claims description 9
IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 claims description 8
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
125000005842 heteroatom Chemical group 0.000 claims description 8
WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 8
229940091173 hydantoin Drugs 0.000 claims description 8
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 8
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
125000005530 alkylenedioxy group Chemical group 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
229910052717 sulfur Inorganic materials 0.000 claims description 6
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
125000004391 aryl sulfonyl group Chemical group 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
238000011321 prophylaxis Methods 0.000 claims description 5
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
125000003368 amide group Chemical group 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
229910052799 carbon Inorganic materials 0.000 claims description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 claims description 4
125000001425 triazolyl group Chemical group 0.000 claims description 4
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 3
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
125000002619 bicyclic group Chemical group 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
ORLCYMQZIPSODD-UHFFFAOYSA-N 1-chloro-2-[chloro(2,2,2-trichloroethoxy)phosphoryl]oxybenzene Chemical compound ClC1=CC=CC=C1OP(Cl)(=O)OCC(Cl)(Cl)Cl ORLCYMQZIPSODD-UHFFFAOYSA-N 0.000 claims description 2
125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 2
AUNXAUMTLBKWDN-UHFFFAOYSA-N 6-[[4-[2-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperazin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCN1C1=CC=CC=C1OCCN1CCN(C)CC1 AUNXAUMTLBKWDN-UHFFFAOYSA-N 0.000 claims description 2
HOLAMNFRWUTIPH-UHFFFAOYSA-N 6-[[4-[3-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperazin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCN1C(C=1)=CC=CC=1OCCN1CCN(C)CC1 HOLAMNFRWUTIPH-UHFFFAOYSA-N 0.000 claims description 2
GIGXDLIAJGQRAQ-UHFFFAOYSA-N 6-[[4-[3-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCC1C(C=1)=CC=CC=1OCCN1CCN(C)CC1 GIGXDLIAJGQRAQ-UHFFFAOYSA-N 0.000 claims description 2
MXALDIZMZILEHT-UHFFFAOYSA-N 6-[[4-[3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCC1C(C=1)=CC=CC=1OCCCN1CCN(C)CC1 MXALDIZMZILEHT-UHFFFAOYSA-N 0.000 claims description 2
FNPBVCDOFHULAQ-UHFFFAOYSA-N 6-[[4-[4-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperazin-1-yl]methyl]-7-(2-methylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical group C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCN1C(C=C1)=CC=C1OCCN1CCN(C)CC1 FNPBVCDOFHULAQ-UHFFFAOYSA-N 0.000 claims description 2
OPSCDEKVNNNUFM-UHFFFAOYSA-N 6-[[4-[4-[2-(dimethylamino)ethoxy]phenyl]piperidin-1-yl]methyl]-7-(2,2-dimethylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1=CC(OCCN(C)C)=CC=C1C1CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 OPSCDEKVNNNUFM-UHFFFAOYSA-N 0.000 claims description 2
LMHQISUNQXUKHX-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[2-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCOC1=CC=CC=C1C1CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 LMHQISUNQXUKHX-UHFFFAOYSA-N 0.000 claims description 2
QVMOSOJJSBKNLJ-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[2-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC=CC=C1C1CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 QVMOSOJJSBKNLJ-UHFFFAOYSA-N 0.000 claims description 2
AOGHZCDVVFVDEP-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[3-[2-(4-methylpiperazin-1-yl)ethoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCOC1=CC=CC(C2CCN(CC=3N(C4=NC(=NC=C4C=3)C#N)CC(C)(C)C)CC2)=C1 AOGHZCDVVFVDEP-UHFFFAOYSA-N 0.000 claims description 2
KNUDRFYJFMJIEO-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[3-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC=CC(C2CCN(CC=3N(C4=NC(=NC=C4C=3)C#N)CC(C)(C)C)CC2)=C1 KNUDRFYJFMJIEO-UHFFFAOYSA-N 0.000 claims description 2
PYBRNWJJSLVOSI-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[4-(2-pyrrolidin-1-ylethoxy)phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)(C)C)C=1CN(CC1)CCC1C(C=C1)=CC=C1OCCN1CCCC1 PYBRNWJJSLVOSI-UHFFFAOYSA-N 0.000 claims description 2
OUUAIGGCPYHJKU-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[4-[3-(4-methylpiperazin-1-yl)propoxy]phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C1CN(C)CCN1CCCOC1=CC=C(C2CCN(CC=3N(C4=NC(=NC=C4C=3)C#N)CC(C)(C)C)CC2)C=C1 OUUAIGGCPYHJKU-UHFFFAOYSA-N 0.000 claims description 2
MAFAZFPSXCIMMT-UHFFFAOYSA-N 7-(2-methylpropyl)-6-[[4-[4-(2-pyrrolidin-1-ylethoxy)phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)C)C=1CN(CC1)CCC1C(C=C1)=CC=C1OCCN1CCCC1 MAFAZFPSXCIMMT-UHFFFAOYSA-N 0.000 claims description 2
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims description 2
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 claims description 2
QDHFHIQKOVNCNC-UHFFFAOYSA-N butane-1-sulfonic acid Chemical compound CCCCS(O)(=O)=O QDHFHIQKOVNCNC-UHFFFAOYSA-N 0.000 claims description 2
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
239000003814 drug Substances 0.000 claims description 2
125000002541 furyl group Chemical group 0.000 claims description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
125000000842 isoxazolyl group Chemical group 0.000 claims description 2
125000002971 oxazolyl group Chemical group 0.000 claims description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
125000006413 ring segment Chemical group 0.000 claims description 2
125000003003 spiro group Chemical group 0.000 claims description 2
238000006467 substitution reaction Methods 0.000 claims description 2
230000001225 therapeutic effect Effects 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 2
XCLCHALZLMRKMQ-UHFFFAOYSA-N 6-[(6-chloropyrimidin-4-yl)oxymethyl]-7-(2,2-dimethylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)(C)C)C=1COC1=CC(Cl)=NC=N1 XCLCHALZLMRKMQ-UHFFFAOYSA-N 0.000 claims 1
CDZBRYFIHGHOAJ-UHFFFAOYSA-N 6-[[4-(2,4-dimethoxyphenyl)piperidin-1-yl]methyl]-7-(2,2-dimethylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound COC1=CC(OC)=CC=C1C1CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 CDZBRYFIHGHOAJ-UHFFFAOYSA-N 0.000 claims 1
ZDJLKHADBWOJQU-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[(1-ethyl-2,4-dioxo-1,3,8-triazaspiro[4.5]decan-8-yl)methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound CCN1C(=O)NC(=O)C11CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 ZDJLKHADBWOJQU-UHFFFAOYSA-N 0.000 claims 1
GXOJVJRVBSWEIY-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[(1-methyl-2,4-dioxo-3-propyl-1,3,8-triazaspiro[4.5]decan-8-yl)methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound O=C1N(CCC)C(=O)N(C)C11CCN(CC=2N(C3=NC(=NC=C3C=2)C#N)CC(C)(C)C)CC1 GXOJVJRVBSWEIY-UHFFFAOYSA-N 0.000 claims 1
ZUFKLYQKICZFHV-UHFFFAOYSA-N 7-(2,2-dimethylpropyl)-6-[[4-[2-(2-pyrrolidin-1-ylethoxy)phenyl]piperidin-1-yl]methyl]pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound C=1C2=CN=C(C#N)N=C2N(CC(C)(C)C)C=1CN(CC1)CCC1C1=CC=CC=C1OCCN1CCCC1 ZUFKLYQKICZFHV-UHFFFAOYSA-N 0.000 claims 1
XYPKNCIOPIPZEG-UHFFFAOYSA-N 8-(bromomethyl)-9-(2,2-dimethylpropyl)purine-2-carbonitrile Chemical compound N1=C(C#N)N=C2N(CC(C)(C)C)C(CBr)=NC2=C1 XYPKNCIOPIPZEG-UHFFFAOYSA-N 0.000 claims 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims 1
DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 1
150000001732 carboxylic acid derivatives Chemical class 0.000 claims 1
ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims 1
125000001041 indolyl group Chemical group 0.000 claims 1
JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 336
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 291
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 195
239000000203 mixture Substances 0.000 description 157
239000000243 solution Substances 0.000 description 131
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 116
238000005160 1H NMR spectroscopy Methods 0.000 description 114
239000012267 brine Substances 0.000 description 113
239000011541 reaction mixture Substances 0.000 description 113
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 113
239000000047 product Substances 0.000 description 86
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 81
229910001868 water Inorganic materials 0.000 description 72
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
239000000284 extract Substances 0.000 description 68
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 68
238000010898 silica gel chromatography Methods 0.000 description 67
238000000034 method Methods 0.000 description 62
239000012044 organic layer Substances 0.000 description 60
239000007858 starting material Substances 0.000 description 59
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 58
229910052943 magnesium sulfate Inorganic materials 0.000 description 58
235000019341 magnesium sulphate Nutrition 0.000 description 58
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
230000002829 reductive effect Effects 0.000 description 52
238000006243 chemical reaction Methods 0.000 description 51
239000000741 silica gel Substances 0.000 description 51
229910002027 silica gel Inorganic materials 0.000 description 51
239000002904 solvent Substances 0.000 description 40
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
229910000027 potassium carbonate Inorganic materials 0.000 description 35
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 34
235000019439 ethyl acetate Nutrition 0.000 description 34
229910052938 sodium sulfate Inorganic materials 0.000 description 34
235000011152 sodium sulphate Nutrition 0.000 description 34
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 33
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
239000012299 nitrogen atmosphere Substances 0.000 description 25
SVNIABUZGXNWNA-UHFFFAOYSA-N 6-(bromomethyl)-7-(2,2-dimethylpropyl)pyrrolo[2,3-d]pyrimidine-2-carbonitrile Chemical compound N1=C(C#N)N=C2N(CC(C)(C)C)C(CBr)=CC2=C1 SVNIABUZGXNWNA-UHFFFAOYSA-N 0.000 description 24
235000011181 potassium carbonates Nutrition 0.000 description 24
238000003756 stirring Methods 0.000 description 23
239000012043 crude product Substances 0.000 description 22
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
239000000725 suspension Substances 0.000 description 20
238000004440 column chromatography Methods 0.000 description 19
238000000746 purification Methods 0.000 description 19
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
239000003480 eluent Substances 0.000 description 16
239000007787 solid Substances 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 15
239000000706 filtrate Substances 0.000 description 15
238000001816 cooling Methods 0.000 description 13
238000001704 evaporation Methods 0.000 description 13
230000008020 evaporation Effects 0.000 description 13
239000005457 ice water Substances 0.000 description 13
239000011734 sodium Substances 0.000 description 13
WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 13
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P35/02—Antineoplastic agents specific for leukemia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Pharmacology & Pharmacy (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
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Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Oncology (AREA)
Orthopedic Medicine & Surgery (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Neurosurgery (AREA)
Urology & Nephrology (AREA)
Transplantation (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Vascular Medicine (AREA)
Communicable Diseases (AREA)
Pain & Pain Management (AREA)
Hematology (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO20041180A 2001-08-30 2004-03-19 Pyrrolopyrimidiner, anvendelse derav og farmasoytisk sammensetning omfattende en slik forbindelse NO328890B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GBGB0121033.5A GB0121033D0 (en)	2001-08-30	2001-08-30	Organic compounds
PCT/EP2002/009663 WO2003020721A1 (en)	2001-08-30	2002-08-29	Pyrrolo pyrimidines as agents for the inhibition of cystein proteases

Publications (2)

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NO20041180L NO20041180L (no)	2004-03-19
NO328890B1 true NO328890B1 (no)	2010-06-07

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Country Status (29)

Country	Link
US (2)	US7452886B2 (es)
EP (1)	EP1423391B8 (es)
JP (1)	JP4629334B2 (es)
KR (1)	KR100695845B1 (es)
CN (1)	CN100372849C (es)
AR (1)	AR036374A1 (es)
AT (1)	ATE326469T1 (es)
AU (1)	AU2002333760B2 (es)
BR (1)	BR0212226A (es)
CA (1)	CA2458684C (es)
CY (1)	CY1105573T1 (es)
DE (1)	DE60211530T2 (es)
DK (1)	DK1423391T3 (es)
EC (1)	ECSP044998A (es)
ES (1)	ES2262888T3 (es)
GB (1)	GB0121033D0 (es)
HU (1)	HUP0401301A3 (es)
IL (3)	IL160367A0 (es)
MX (1)	MXPA04001935A (es)
MY (1)	MY157368A (es)
NO (1)	NO328890B1 (es)
NZ (1)	NZ531343A (es)
PE (1)	PE20030418A1 (es)
PL (1)	PL368280A1 (es)
PT (1)	PT1423391E (es)
RU (1)	RU2331644C2 (es)
TW (1)	TWI297690B (es)
WO (1)	WO2003020721A1 (es)
ZA (1)	ZA200401042B (es)

Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20030144234A1 (en) *	2001-08-30	2003-07-31	Buxton Francis Paul	Methods for the treatment of chronic pain and compositions therefor
SE0201980D0 (sv) *	2002-06-24	2002-06-24	Astrazeneca Ab	Novel compounds
GB0220187D0 (en)	2002-08-30	2002-10-09	Novartis Ag	Organic compounds
KR101095807B1 (ko)	2002-09-24	2011-12-21	노파르티스 아게	탈수초성 장애의 치료에 있어서의 스핑고신-1-포스페이트 수용체 아고니스트
AR043692A1 (es) *	2003-02-06	2005-08-10	Novartis Ag	2-cianopirrolopirimidinas y sus usos farmaceuticos
GB0304640D0 (en) *	2003-02-28	2003-04-02	Novartis Ag	Organic compounds
JP4710606B2 (ja) *	2003-04-18	2011-06-29	小野薬品工業株式会社	スピロピペリジン化合物およびその医薬用途
MXPA05011593A (es) *	2003-04-28	2005-12-15	Novartis Ag	Composicion farmaceutica que comprende un inhibidor de catepsina s y un opioide.
EP1797883A3 (en) *	2003-04-28	2007-08-01	Novartis AG	Pharmaceutical composition comprising a cathepsin S inhibitor and an opioid
CA2523085A1 (en) *	2003-04-30	2004-11-18	Fmc Corporation	Insecticidal (dihalopropenyl) phenylalkyl substituted dihydrobenzofuran and dihydrobenzopyran derivatives
WO2005011703A1 (en) *	2003-08-04	2005-02-10	Akzo Nobel N.V.	2-cyano-1,3,5-triazine-4,6-diamine derivatives
EP1786816A4 (en) *	2003-09-10	2009-11-04	Virochem Pharma Inc	SPIROHYDANTOIN COMPOUNDS AND METHODS FOR MODULATING CHEMOKINE RECEPTOR ACTIVITY
MXPA06009019A (es)	2004-02-18	2007-03-08	Astrazeneca Ab	Compuestos de tetrazol y su uso como antagonistas del receptor de glutamato metabotropico.
US20070197510A1 (en) *	2004-03-10	2007-08-23	Kazuyuki Ohmoto	Nitriles and medicinal compositions containing the same as the active ingredient
ES2251292B1 (es)	2004-04-20	2007-07-01	Inke, S.A.	Procedimiento para la obtencion de un compuesto farmaceuticamente activo y de sus intermedios de sintesis.
CN1980934B (zh)	2004-05-03	2011-10-26	詹森药业有限公司	作为选择性雄激素受体调节剂（sarms）的新的吲哚衍生物
TW200614993A (en)	2004-06-11	2006-05-16	Akzo Nobel Nv	4-phenyl-pyrimidine-2-carbonitrile derivatives
US7951816B2 (en)	2004-08-27	2011-05-31	Ono Pharmaceutical Co., Ltd.	Compound containing basic group and use thereof
KR100651849B1 (ko) *	2005-02-01	2006-12-01	엘지전자 주식회사	세탁기
RU2424234C2 (ru) *	2005-08-05	2011-07-20	Ибриженикс Са	Новые ингибиторы цистеиновых протеаз и их терапевтическое применение
AU2006286489B2 (en)	2005-09-01	2012-08-09	Ares Trading S.A.	Treatment of optic neuritis
TW200745055A (en) *	2005-09-23	2007-12-16	Organon Nv	4-Phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives
US7326715B2 (en)	2005-09-23	2008-02-05	N.V. Organon	4-Phenyl-6-substituted-pyrimidine-2-carbonitrile derivatives
AR056720A1 (es) *	2005-10-26	2007-10-17	Smithkline Beecham Corp	Compuesto de tiazol substtuido composicion farmaceuticamente que lo comprende y su uso para preparar un medicamento
WO2007058322A1 (ja)	2005-11-18	2007-05-24	Ono Pharmaceutical Co., Ltd.	塩基性基を含有する化合物およびその用途
EP1957494A2 (en) *	2005-12-05	2008-08-20	Incyte Corporation	Lactam compounds and methods of using the same
US7687515B2 (en)	2006-01-17	2010-03-30	N.V. Organon	6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives
US8618122B2 (en)	2006-05-16	2013-12-31	Ono Pharmaceutical Co., Ltd.	Compound having acidic group which may be protected, and use thereof
WO2008032191A2 (en)	2006-09-13	2008-03-20	Astrazeneca Ab	Spiro-oxazolidinone compounds and their use as metabotropic glutamate receptor potentiators
TW200911803A (en) *	2007-07-16	2009-03-16	Organon Nv	6-phenyl-1H-imidazo [4,5-c] pyridine-4-carbonitrile derivatives
US7932251B2 (en)	2007-07-16	2011-04-26	N.V. Organon	6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives
AU2008312055A1 (en)	2007-10-19	2009-04-23	Astrazeneca Ab	Tetrazole derivatives as modulators of metabotropic glutamate receptors (mGluRs)
JP2011525189A (ja)	2008-06-20	2011-09-15	ノバルティスアーゲー	多発性硬化症を治療するための小児科の組成物
TW201035094A (en)	2009-01-16	2010-10-01	Organon Nv	6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives
US8026236B2 (en)	2009-01-16	2011-09-27	N.V. Organon	6-phenyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile derivatives
CA2766100C (en)	2009-06-29	2018-05-22	Incyte Corporation	Pyrimidinones as pi3k inhibitors
WO2011075643A1 (en)	2009-12-18	2011-06-23	Incyte Corporation	Substituted heteroaryl fused derivatives as pi3k inhibitors
CN102892768A (zh)	2009-12-30	2013-01-23	艾科尔公司	被取代的吡咯并氨基嘧啶化合物
EP2523954B1 (en)	2010-01-15	2014-04-16	Merck Sharp & Dohme B.V.	1h-[1,2,3]triazolo[4,5-c]pyridine-4- carbonitrile derivatives as cathepsin s inhibitors
WO2011130342A1 (en)	2010-04-14	2011-10-20	Incyte Corporation	FUSED DERIVATIVES AS ΡI3Κδ INHIBITORS
WO2011163195A1 (en)	2010-06-21	2011-12-29	Incyte Corporation	Fused pyrrole derivatives as pi3k inhibitors
WO2012027495A1 (en)	2010-08-27	2012-03-01	University Of The Pacific	Piperazinylpyrimidine analogues as protein kinase inhibitors
EP2626431B1 (en)	2010-10-06	2015-09-16	Fundació Institut de Recerca Biomèdica (IRB Barcelona)	Method for the diagnosis, prognosis and treatment of breast cancer metastasis
ES2764848T3 (es)	2010-12-20	2020-06-04	Incyte Holdings Corp	N-(1-(fenilo sustituido)etilo)-9H-purina-6-aminas como inhibidores de PI3K
WO2012125629A1 (en)	2011-03-14	2012-09-20	Incyte Corporation	Substituted diamino-pyrimidine and diamino-pyridine derivatives as pi3k inhibitors
US9126948B2 (en)	2011-03-25	2015-09-08	Incyte Holdings Corporation	Pyrimidine-4,6-diamine derivatives as PI3K inhibitors
KR102131612B1 (ko)	2011-09-02	2020-07-08	인사이트 홀딩스 코포레이션	Ｐｉ３ｋ 억제제로서 헤테로시클릴아민
AR090548A1 (es)	2012-04-02	2014-11-19	Incyte Corp	Azaheterociclobencilaminas biciclicas como inhibidores de pi3k
EP2650682A1 (en)	2012-04-09	2013-10-16	Fundació Privada Institut de Recerca Biomèdica	Method for the prognosis and treatment of cancer metastasis
MX355055B (es) *	2012-04-17	2018-04-03	Astellas Pharma Inc	Compuesto heterociclico aromatico biciclico nitrogenado.
CN104603288B (zh)	2012-06-06	2018-12-14	生物医学研究机构基金会	用于肺癌转移的诊断、预后和治疗的方法
US10119171B2 (en)	2012-10-12	2018-11-06	Inbiomotion S.L.	Method for the diagnosis, prognosis and treatment of prostate cancer metastasis
HK1213946A1 (zh)	2012-10-12	2016-07-15	Inbiomotion S.L.	用於使用c-maf对前列腺癌转移进行诊断、预後和治疗的方法
US20160032399A1 (en)	2013-03-15	2016-02-04	Inbiomotion S.L.	Method for the Prognosis and Treatment of Renal Cell Carcinoma Metastasis
US20160032400A1 (en)	2013-03-15	2016-02-04	Fundació Institut De Recerca Biomèdica (Irb Barcelona)	Method for the prognosis and treatment of cancer metastasis
EP3055429B1 (en)	2013-10-09	2019-03-27	Fundació Institut de Recerca Biomèdica (IRB Barcelona)	Method for the prognosis and treatment of metastasizing cancer of the bone originating from breast cancer
WO2015191677A1 (en)	2014-06-11	2015-12-17	Incyte Corporation	Bicyclic heteroarylaminoalkyl phenyl derivatives as pi3k inhibitors
EP3229909B1 (en)	2014-12-11	2020-10-14	Inbiomotion S.L.	Binding members for human c-maf
SI3831833T1 (sl)	2015-02-27	2023-03-31	Incyte Holdings Corporation	Postopki za pripravo inhibitorja PI3K
WO2016183063A1 (en)	2015-05-11	2016-11-17	Incyte Corporation	Crystalline forms of a pi3k inhibitor
WO2016183060A1 (en)	2015-05-11	2016-11-17	Incyte Corporation	Process for the synthesis of a phosphoinositide 3-kinase inhibitor
KR102867720B1 (ko)	2016-05-25	2025-10-01	인바이오모션 에스.엘.	c-MAF 상태에 기초한 유방암의 치료
AU2018372762B2 (en)	2017-11-22	2025-08-21	Inbiomotion S.L.	Therapeutic treatment of breast cancer based on c-maf status
KR102054910B1 (ko) *	2017-12-19	2019-12-12	한림제약(주)	피롤로[2,3-d]피리미딘 유도체 또는 이의 염 및 이를 포함하는 약학 조성물
EP3781156A4 (en)	2018-04-16	2022-05-18	C4 Therapeutics, Inc.	SPIROCYCLIC COMPOUNDS
EP3556760A1 (en) *	2018-04-19	2019-10-23	F. Hoffmann-La Roche AG	Spiro compounds
IL278889B2 (en)	2018-06-01	2025-11-01	Incyte Corp	Dosing regimen for the treatment of pi3k related disorders
WO2020201572A1 (en)	2019-04-05	2020-10-08	Université De Bretagne Occidentale	Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning
WO2022226166A1 (en) *	2021-04-22	2022-10-27	Protego Biopharma, Inc.	Spirocyclic imidazolidinones and imidazolidinediones for treatment of light chain amyloidosis
CA3239086A1 (en) *	2021-12-01	2023-06-08	St Pharm Co., Ltd.	Method for preparing triazolopyrimidinone derivative

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE1251074B (de)	1960-11-02	1967-09-28	J R Geigy A -G , Basel (Schweiz)	Selektives Herbizid
CH627919A5 (de)	1977-04-14	1982-02-15	Ciba Geigy Ag	Herbizide mittel.
US5958930A (en) *	1991-04-08	1999-09-28	Duquesne University Of The Holy Ghost	Pyrrolo pyrimidine and furo pyrimidine derivatives
DK0682027T3 (da) *	1994-05-03	1998-05-04	Ciba Geigy Ag	Pyrrolopyrimidinderivater med antiproliferativ virkning
US5683999A (en) *	1995-03-17	1997-11-04	The Dupont Merck Pharmaceutical Company	Cyclic urea HIV protease inhibitors
DK0831829T3 (da) *	1995-06-07	2003-12-15	Pfizer	Heterocykliske, ringkondenserede pyrimidinderivater
CA2283961A1 (en) *	1997-03-19	1998-09-24	Basf Aktiengesellschaft	Pyrrolo[2,3d]pyrimidines and their use as tyrosine kinase inhibitors
JP2002519325A (ja) *	1998-06-30	2002-07-02	イーライ・リリー・アンド・カンパニー	二環性ｓＰＬＡ２インヒビター
CA2344249A1 (en) *	1998-09-18	2000-03-30	Basf Aktiengesellschaft	Pyrrolopyrimidines as protein kinase inhibitors
JP4078074B2 (ja) *	1999-12-10	2008-04-23	ファイザー・プロダクツ・インク	ピロロ［２，３−ｄ］ピリミジン化合物
EP1265897A1 (en) *	2000-03-20	2002-12-18	Axys Pharmaceuticals, Inc.	Non-amidine containing protease inhibitors
WO2001083460A1 (en)	2000-04-28	2001-11-08	Tanabe Seiyaku Co., Ltd.	Cyclic compounds

2001
- 2001-08-30 GB GBGB0121033.5A patent/GB0121033D0/en not_active Ceased
2002
- 2002-08-27 MY MYPI20023181A patent/MY157368A/en unknown
- 2002-08-28 AR ARP020103229A patent/AR036374A1/es unknown
- 2002-08-28 TW TW091119570A patent/TWI297690B/zh not_active IP Right Cessation
- 2002-08-29 WO PCT/EP2002/009663 patent/WO2003020721A1/en not_active Ceased
- 2002-08-29 HU HU0401301A patent/HUP0401301A3/hu unknown
- 2002-08-29 AT AT02797553T patent/ATE326469T1/de active
- 2002-08-29 KR KR1020047003048A patent/KR100695845B1/ko not_active Expired - Fee Related
- 2002-08-29 PE PE2002000833A patent/PE20030418A1/es not_active Application Discontinuation
- 2002-08-29 ES ES02797553T patent/ES2262888T3/es not_active Expired - Lifetime
- 2002-08-29 PL PL02368280A patent/PL368280A1/xx not_active Application Discontinuation
- 2002-08-29 RU RU2004109815/04A patent/RU2331644C2/ru not_active IP Right Cessation
- 2002-08-29 CA CA002458684A patent/CA2458684C/en not_active Expired - Fee Related
- 2002-08-29 JP JP2003524991A patent/JP4629334B2/ja not_active Expired - Fee Related
- 2002-08-29 MX MXPA04001935A patent/MXPA04001935A/es active IP Right Grant
- 2002-08-29 NZ NZ531343A patent/NZ531343A/en not_active IP Right Cessation
- 2002-08-29 AU AU2002333760A patent/AU2002333760B2/en not_active Ceased
- 2002-08-29 CN CNB028168402A patent/CN100372849C/zh not_active Expired - Fee Related
- 2002-08-29 IL IL16036702A patent/IL160367A0/xx unknown
- 2002-08-29 PT PT02797553T patent/PT1423391E/pt unknown
- 2002-08-29 DE DE60211530T patent/DE60211530T2/de not_active Expired - Lifetime
- 2002-08-29 BR BR0212226-0A patent/BR0212226A/pt not_active Application Discontinuation
- 2002-08-29 DK DK02797553T patent/DK1423391T3/da active
- 2002-08-29 US US10/487,760 patent/US7452886B2/en not_active Expired - Fee Related
- 2002-08-29 EP EP02797553A patent/EP1423391B8/en not_active Expired - Lifetime
2004
- 2004-02-09 ZA ZA200401042A patent/ZA200401042B/en unknown
- 2004-02-12 IL IL160367A patent/IL160367A/en not_active IP Right Cessation
- 2004-03-01 EC EC2004004998A patent/ECSP044998A/es unknown
- 2004-03-19 NO NO20041180A patent/NO328890B1/no not_active IP Right Cessation
2006
- 2006-08-03 CY CY20061101095T patent/CY1105573T1/el unknown
2008
- 2008-09-25 US US12/237,896 patent/US20090054467A1/en not_active Abandoned
2009
- 2009-05-07 IL IL198643A patent/IL198643A/en not_active IP Right Cessation

Also Published As

Publication number	Publication date
TWI297690B (en)	2008-06-11
RU2331644C2 (ru)	2008-08-20
DE60211530D1 (de)	2006-06-22
CA2458684A1 (en)	2003-03-13
EP1423391B1 (en)	2006-05-17
ZA200401042B (en)	2004-10-25
MY157368A (en)	2016-06-15
US7452886B2 (en)	2008-11-18
IL198643A (en)	2010-12-30
NZ531343A (en)	2006-01-27
KR100695845B1 (ko)	2007-03-20
ECSP044998A (es)	2004-04-28
AU2002333760B2 (en)	2007-01-04
PE20030418A1 (es)	2003-06-12
US20050054851A1 (en)	2005-03-10
IL160367A (en)	2009-12-24
MXPA04001935A (es)	2004-06-15
CA2458684C (en)	2009-04-07
HUP0401301A3 (en)	2008-03-28
DK1423391T3 (da)	2006-09-25
NO20041180L (no)	2004-03-19
GB0121033D0 (en)	2001-10-24
EP1423391B8 (en)	2007-12-12
IL160367A0 (en)	2004-07-25
CN1549817A (zh)	2004-11-24
KR20040029123A (ko)	2004-04-03
JP2005502683A (ja)	2005-01-27
DE60211530T2 (de)	2006-12-21
PL368280A1 (en)	2005-03-21
CN100372849C (zh)	2008-03-05
AR036374A1 (es)	2004-09-01
ES2262888T3 (es)	2006-12-01
WO2003020721A1 (en)	2003-03-13
ATE326469T1 (de)	2006-06-15
US20090054467A1 (en)	2009-02-26
BR0212226A (pt)	2004-08-17
PT1423391E (pt)	2006-09-29
HK1072254A1 (zh)	2005-08-19
RU2004109815A (ru)	2005-10-20
CY1105573T1 (el)	2010-07-28
EP1423391A1 (en)	2004-06-02
JP4629334B2 (ja)	2011-02-09
HUP0401301A2 (hu)	2004-10-28

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