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
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- 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
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- 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
- 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)
Animal Behavior & Ethology (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Physical Education & Sports Medicine (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Oncology (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Transplantation (AREA)
Biomedical Technology (AREA)
Communicable Diseases (AREA)
Neurosurgery (AREA)
Hematology (AREA)
Pulmonology (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
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)

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

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

Country Status (29)

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

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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 TW TW091119570A patent/TWI297690B/zh not_active IP Right Cessation
- 2002-08-28 AR ARP020103229A patent/AR036374A1/es unknown
- 2002-08-29 CA CA002458684A patent/CA2458684C/en not_active Expired - Fee Related
- 2002-08-29 PL PL02368280A patent/PL368280A1/xx not_active Application Discontinuation
- 2002-08-29 DE DE60211530T patent/DE60211530T2/de not_active Expired - Lifetime
- 2002-08-29 HU HU0401301A patent/HUP0401301A3/hu unknown
- 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 BR BR0212226-0A patent/BR0212226A/pt not_active Application Discontinuation
- 2002-08-29 WO PCT/EP2002/009663 patent/WO2003020721A1/en not_active Ceased
- 2002-08-29 PT PT02797553T patent/PT1423391E/pt unknown
- 2002-08-29 EP EP02797553A patent/EP1423391B8/en not_active Expired - Lifetime
- 2002-08-29 RU RU2004109815/04A patent/RU2331644C2/ru not_active IP Right Cessation
- 2002-08-29 MX MXPA04001935A patent/MXPA04001935A/es active IP Right Grant
- 2002-08-29 IL IL16036702A patent/IL160367A0/xx unknown
- 2002-08-29 PE PE2002000833A patent/PE20030418A1/es not_active Application Discontinuation
- 2002-08-29 AU AU2002333760A patent/AU2002333760B2/en not_active Ceased
- 2002-08-29 NZ NZ531343A patent/NZ531343A/en not_active IP Right Cessation
- 2002-08-29 ES ES02797553T patent/ES2262888T3/es not_active Expired - Lifetime
- 2002-08-29 AT AT02797553T patent/ATE326469T1/de active
- 2002-08-29 CN CNB028168402A patent/CN100372849C/zh not_active Expired - Fee Related
- 2002-08-29 JP JP2003524991A patent/JP4629334B2/ja not_active Expired - Fee Related
- 2002-08-29 KR KR1020047003048A patent/KR100695845B1/ko not_active Expired - Fee Related
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
PT1423391E (pt)	2006-09-29
NZ531343A (en)	2006-01-27
ZA200401042B (en)	2004-10-25
JP2005502683A (ja)	2005-01-27
ES2262888T3 (es)	2006-12-01
CN1549817A (zh)	2004-11-24
PL368280A1 (en)	2005-03-21
GB0121033D0 (en)	2001-10-24
CA2458684C (en)	2009-04-07
US20050054851A1 (en)	2005-03-10
AR036374A1 (es)	2004-09-01
CY1105573T1 (el)	2010-07-28
CA2458684A1 (en)	2003-03-13
MXPA04001935A (es)	2004-06-15
EP1423391A1 (en)	2004-06-02
DE60211530D1 (de)	2006-06-22
IL198643A (en)	2010-12-30
AU2002333760B2 (en)	2007-01-04
MY157368A (en)	2016-06-15
TWI297690B (en)	2008-06-11
KR20040029123A (ko)	2004-04-03
EP1423391B1 (en)	2006-05-17
PE20030418A1 (es)	2003-06-12
US7452886B2 (en)	2008-11-18
IL160367A (en)	2009-12-24
NO20041180L (no)	2004-03-19
CN100372849C (zh)	2008-03-05
IL160367A0 (en)	2004-07-25
DK1423391T3 (da)	2006-09-25
HUP0401301A3 (en)	2008-03-28
EP1423391B8 (en)	2007-12-12
BR0212226A (pt)	2004-08-17
ATE326469T1 (de)	2006-06-15
RU2331644C2 (ru)	2008-08-20
WO2003020721A1 (en)	2003-03-13
HK1072254A1 (zh)	2005-08-19
KR100695845B1 (ko)	2007-03-20
HUP0401301A2 (hu)	2004-10-28
RU2004109815A (ru)	2005-10-20
ECSP044998A (es)	2004-04-28
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