SK14562001A3 - Substituované azoly, spôsob ich prípravy, farmaceutická kompozícia s ich obsahom a ich použitie - Google Patents

Substituované azoly, spôsob ich prípravy, farmaceutická kompozícia s ich obsahom a ich použitie Download PDF

Info

Publication number: SK14562001A3
Authority: SK; Slovakia
Prior art keywords: fluorophenyl; amino; pyrimidyl; alkyl; group
Prior art date: 1999-04-14

Application number

SK1456-2001A

Other languages

English (en)

Slovak (sk)

Inventor

L�Szlo R�V�Sz

Achim Schlapbach

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.)

1999-04-14

Filing date

2000-04-12

Publication date

2002-03-05

1999-04-14 Priority claimed from GBGB9908532.6A external-priority patent/GB9908532D0/en

1999-04-14 Priority claimed from GBGB9908531.8A external-priority patent/GB9908531D0/en

2000-04-12 Application filed by Novartis Ag filed Critical Novartis Ag

2002-03-05 Publication of SK14562001A3 publication Critical patent/SK14562001A3/sk

Links

238000000034 method Methods 0.000 title claims description 20
238000002360 preparation method Methods 0.000 title claims description 4
239000008194 pharmaceutical composition Substances 0.000 title claims description 3
150000003851 azoles Chemical class 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 141
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 173
-1 CF 3 Chemical group 0.000 claims description 157
125000004432 carbon atom Chemical group C* 0.000 claims description 80
125000000217 alkyl group Chemical group 0.000 claims description 73
229910052736 halogen Inorganic materials 0.000 claims description 63
150000002367 halogens Chemical group 0.000 claims description 63
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 60
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 56
229910052757 nitrogen Inorganic materials 0.000 claims description 40
125000001424 substituent group Chemical group 0.000 claims description 33
239000002253 acid Substances 0.000 claims description 28
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
125000003545 alkoxy group Chemical group 0.000 claims description 27
229910052739 hydrogen Inorganic materials 0.000 claims description 26
239000001257 hydrogen Substances 0.000 claims description 25
125000004433 nitrogen atom Chemical group N* 0.000 claims description 25
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 24
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 23
125000003118 aryl group Chemical group 0.000 claims description 22
125000000753 cycloalkyl group Chemical group 0.000 claims description 22
150000002148 esters Chemical class 0.000 claims description 22
125000001072 heteroaryl group Chemical group 0.000 claims description 22
125000005842 heteroatom Chemical group 0.000 claims description 22
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 21
229910052799 carbon Inorganic materials 0.000 claims description 19
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 19
125000005843 halogen group Chemical group 0.000 claims description 18
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 17
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 14
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 13
125000006413 ring segment Chemical group 0.000 claims description 12
125000003710 aryl alkyl group Chemical group 0.000 claims description 11
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 11
108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 10
125000004414 alkyl thio group Chemical group 0.000 claims description 10
125000002947 alkylene group Chemical group 0.000 claims description 10
125000003368 amide group Chemical group 0.000 claims description 10
125000004093 cyano group Chemical group *C#N 0.000 claims description 10
125000004076 pyridyl group Chemical group 0.000 claims description 10
238000011282 treatment Methods 0.000 claims description 10
150000001412 amines Chemical class 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 8
OMOCVUPRTIPABZ-UHFFFAOYSA-N 1-(1h-imidazol-2-yl)piperidine Chemical compound C1CCCCN1C1=NC=CN1 OMOCVUPRTIPABZ-UHFFFAOYSA-N 0.000 claims description 8
125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 8
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 8
125000003386 piperidinyl group Chemical group 0.000 claims description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
125000004663 dialkyl amino group Chemical group 0.000 claims description 7
125000002757 morpholinyl group Chemical group 0.000 claims description 7
125000004193 piperazinyl group Chemical group 0.000 claims description 7
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
125000001831 (C6-C10) heteroaryl group Chemical group 0.000 claims description 6
RGEMRXMFQPBDKB-IBGZPJMESA-N 4-[2-(4-fluorophenyl)-4-piperidin-1-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(N2CCCCC2)N=C1C1=CC=C(F)C=C1 RGEMRXMFQPBDKB-IBGZPJMESA-N 0.000 claims description 6
150000007942 carboxylates Chemical class 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
125000001544 thienyl group Chemical group 0.000 claims description 6
125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 5
102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 5
125000003277 amino group Chemical group 0.000 claims description 5
125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
238000004519 manufacturing process Methods 0.000 claims description 5
239000002243 precursor Substances 0.000 claims description 5
125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 4
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
239000002260 anti-inflammatory agent Substances 0.000 claims description 4
229940121363 anti-inflammatory agent Drugs 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
150000001721 carbon Chemical group 0.000 claims description 4
229960003444 immunosuppressant agent Drugs 0.000 claims description 4
230000001861 immunosuppressant effect Effects 0.000 claims description 4
239000003018 immunosuppressive agent Substances 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 4
125000004953 trihalomethyl group Chemical group 0.000 claims description 4
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
229920002554 vinyl polymer Polymers 0.000 claims description 4
BLNLTPFOJOESQM-SFHVURJKSA-N 4-[2-(4-fluorophenyl)-4-pyridin-4-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2C=CN=CC=2)N=C1C1=CC=C(F)C=C1 BLNLTPFOJOESQM-SFHVURJKSA-N 0.000 claims description 3
HPTDTEXEPXTGON-KRWDZBQOSA-N 4-[2-(4-fluorophenyl)-4-thiophen-3-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C2=CSC=C2)N=C1C1=CC=C(F)C=C1 HPTDTEXEPXTGON-KRWDZBQOSA-N 0.000 claims description 3
FHMNRQWWQTWZMQ-OOJLDXBWSA-N 4-[3-bromo-2-(4-fluorophenyl)-2h-imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=CN(Br)C1C1=CC=C(F)C=C1 FHMNRQWWQTWZMQ-OOJLDXBWSA-N 0.000 claims description 3
VADIUNQAYZTCLW-SFHVURJKSA-N 4-[4-(3-chlorophenyl)-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2C=C(Cl)C=CC=2)N=C1C1=CC=C(F)C=C1 VADIUNQAYZTCLW-SFHVURJKSA-N 0.000 claims description 3
GOYRICSRRPAVRO-INIZCTEOSA-N 4-[4-(5-chlorothiophen-2-yl)-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2SC(Cl)=CC=2)N=C1C1=CC=C(F)C=C1 GOYRICSRRPAVRO-INIZCTEOSA-N 0.000 claims description 3
HEYFMIPJWRNZOJ-UHFFFAOYSA-N 4-[4-bromo-2-[3-(trifluoromethyl)phenyl]imidazol-1-yl]-n-cyclopentylpyrimidin-2-amine Chemical compound FC(F)(F)C1=CC=CC(C=2N(C=C(Br)N=2)C=2N=C(NC3CCCC3)N=CC=2)=C1 HEYFMIPJWRNZOJ-UHFFFAOYSA-N 0.000 claims description 3
GURHPKMAUZMMMN-UHFFFAOYSA-N 4-[4-bromo-2-[3-(trifluoromethyl)phenyl]imidazol-1-yl]-n-cyclopropylpyrimidin-2-amine Chemical compound FC(F)(F)C1=CC=CC(C=2N(C=C(Br)N=2)C=2N=C(NC3CC3)N=CC=2)=C1 GURHPKMAUZMMMN-UHFFFAOYSA-N 0.000 claims description 3
KBONZBOHMUFXCB-INIZCTEOSA-N 4-[4-ethenyl-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=C)N=C1C1=CC=C(F)C=C1 KBONZBOHMUFXCB-INIZCTEOSA-N 0.000 claims description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
206010061218 Inflammation Diseases 0.000 claims description 3
230000004054 inflammatory process Effects 0.000 claims description 3
150000002576 ketones Chemical class 0.000 claims description 3
125000002971 oxazolyl group Chemical group 0.000 claims description 3
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 2
AJDUKCUQHQRXNS-SFHVURJKSA-N 4-[2,4-bis(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2C=CC(F)=CC=2)N=C1C1=CC=C(F)C=C1 AJDUKCUQHQRXNS-SFHVURJKSA-N 0.000 claims description 2
ITGCQBSBVQWQFS-IBGZPJMESA-N 4-[2-(4-ethylpiperazin-1-yl)-4-(4-fluorophenyl)-1,3-oxazol-5-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound C1CN(CC)CCN1C1=NC(C=2C=CC(F)=CC=2)=C(C=2N=C(N[C@@H](C)C=3C=CC=CC=3)N=CC=2)O1 ITGCQBSBVQWQFS-IBGZPJMESA-N 0.000 claims description 2
WOZNUFNHHCRSBL-IBGZPJMESA-N 4-[2-(4-fluorophenyl)-1-[2-[[(1s)-1-phenylethyl]amino]pyrimidin-4-yl]imidazol-4-yl]-1-methylpiperidin-4-ol Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C2(O)CCN(C)CC2)N=C1C1=CC=C(F)C=C1 WOZNUFNHHCRSBL-IBGZPJMESA-N 0.000 claims description 2
XOFQUNFVZPBJMU-IBGZPJMESA-N 4-[2-(4-fluorophenyl)-4-(4-methoxyphenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound C1=CC(OC)=CC=C1C1=CN(C=2N=C(N[C@@H](C)C=3C=CC=CC=3)N=CC=2)C(C=2C=CC(F)=CC=2)=N1 XOFQUNFVZPBJMU-IBGZPJMESA-N 0.000 claims description 2
NMIIJPIOVJUYGH-KRWDZBQOSA-N 4-[2-(4-fluorophenyl)-4-(furan-2-yl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2OC=CC=2)N=C1C1=CC=C(F)C=C1 NMIIJPIOVJUYGH-KRWDZBQOSA-N 0.000 claims description 2
GKNRTYXCNFXLIQ-SFHVURJKSA-N 4-[2-(4-fluorophenyl)-4-pyridin-2-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2N=CC=CC=2)N=C1C1=CC=C(F)C=C1 GKNRTYXCNFXLIQ-SFHVURJKSA-N 0.000 claims description 2
OBGCSBYRWKZXLY-SFHVURJKSA-N 4-[2-(4-fluorophenyl)-4-pyridin-3-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2C=NC=CC=2)N=C1C1=CC=C(F)C=C1 OBGCSBYRWKZXLY-SFHVURJKSA-N 0.000 claims description 2
YHXGGIIVEZOFIA-KRWDZBQOSA-N 4-[2-(4-fluorophenyl)-4-thiophen-2-ylimidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2SC=CC=2)N=C1C1=CC=C(F)C=C1 YHXGGIIVEZOFIA-KRWDZBQOSA-N 0.000 claims description 2
DWVCIXHAUWGUCG-IBGZPJMESA-N 4-[4-(1-benzofuran-2-yl)-2-(4-fluorophenyl)imidazol-1-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1N1C=C(C=2OC3=CC=CC=C3C=2)N=C1C1=CC=C(F)C=C1 DWVCIXHAUWGUCG-IBGZPJMESA-N 0.000 claims description 2
BBICRYPQRHEQGA-KRWDZBQOSA-N 4-[4-(4-fluorophenyl)-2-pyridin-4-yl-1,3-oxazol-5-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1C=1OC(C=2C=CN=CC=2)=NC=1C1=CC=C(F)C=C1 BBICRYPQRHEQGA-KRWDZBQOSA-N 0.000 claims description 2
YYEFWHDWSRRIOJ-UHFFFAOYSA-N 4-[4-bromo-2-[4-(fluoromethyl)phenyl]imidazol-1-yl]-n-cyclohexylpyrimidin-2-amine Chemical compound C1=CC(CF)=CC=C1C1=NC(Br)=CN1C1=CC=NC(NC2CCCCC2)=N1 YYEFWHDWSRRIOJ-UHFFFAOYSA-N 0.000 claims description 2
KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical group NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 claims description 2
RHDNHDHIJPHLRC-UHFFFAOYSA-N N,N-diethyl-2H-1,3-oxazol-3-amine Chemical compound C(C)N(N1COC=C1)CC RHDNHDHIJPHLRC-UHFFFAOYSA-N 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000004475 heteroaralkyl group Chemical group 0.000 claims description 2
230000002401 inhibitory effect Effects 0.000 claims description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
GAWGXNMMMFKVQR-UHFFFAOYSA-N 2-[5-(methylideneamino)-1H-imidazol-2-yl]guanidine Chemical compound C=NC=1N=C(NC=1)NC(=N)N GAWGXNMMMFKVQR-UHFFFAOYSA-N 0.000 claims 1
SDEWHSLEPTWRAI-UHFFFAOYSA-N 4-[1-[2-(cyclohexylamino)pyrimidin-4-yl]-2-(4-fluorophenyl)imidazol-4-yl]-1-methylpiperidin-4-ol Chemical compound C1CN(C)CCC1(O)C1=CN(C=2N=C(NC3CCCCC3)N=CC=2)C(C=2C=CC(F)=CC=2)=N1 SDEWHSLEPTWRAI-UHFFFAOYSA-N 0.000 claims 1
JSHSLFORZWNNNH-IBGZPJMESA-N 4-[4-(4-fluorophenyl)-2-(4-methylpiperidin-1-yl)-1,3-oxazol-5-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1C=1OC(N2CCC(C)CC2)=NC=1C1=CC=C(F)C=C1 JSHSLFORZWNNNH-IBGZPJMESA-N 0.000 claims 1
WQFMURNIPAFPJC-KRWDZBQOSA-N 4-[4-(4-fluorophenyl)-2-piperazin-1-yl-1,3-oxazol-5-yl]-n-[(1s)-1-phenylethyl]pyrimidin-2-amine Chemical compound N([C@@H](C)C=1C=CC=CC=1)C(N=1)=NC=CC=1C=1OC(N2CCNCC2)=NC=1C1=CC=C(F)C=C1 WQFMURNIPAFPJC-KRWDZBQOSA-N 0.000 claims 1
125000000623 heterocyclic group Chemical group 0.000 claims 1
201000010099 disease Diseases 0.000 abstract description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 8
102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 abstract description 6
108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 abstract description 5
108010002352 Interleukin-1 Proteins 0.000 abstract description 4
102000000589 Interleukin-1 Human genes 0.000 abstract description 4
206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
208000001132 Osteoporosis Diseases 0.000 abstract description 3
230000004097 bone metabolism Effects 0.000 abstract description 2
230000001404 mediated effect Effects 0.000 abstract description 2
239000002829 mitogen activated protein kinase inhibitor Substances 0.000 abstract 1
239000000243 solution Substances 0.000 description 110
239000000203 mixture Substances 0.000 description 81
238000001819 mass spectrum Methods 0.000 description 75
238000005160 1H NMR spectroscopy Methods 0.000 description 72
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
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239000011541 reaction mixture Substances 0.000 description 44
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WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 42
229910052938 sodium sulfate Inorganic materials 0.000 description 41
235000011152 sodium sulphate Nutrition 0.000 description 41
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 38
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239000003795 chemical substances by application Substances 0.000 description 27
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 24
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YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
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238000004587 chromatography analysis Methods 0.000 description 15
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102100040247 Tumor necrosis factor Human genes 0.000 description 13
239000008346 aqueous phase Substances 0.000 description 13
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

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Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Immunology (AREA)
Physical Education & Sports Medicine (AREA)
Diabetes (AREA)
Rheumatology (AREA)
Orthopedic Medicine & Surgery (AREA)
Dermatology (AREA)
Pulmonology (AREA)
Hematology (AREA)
Neurology (AREA)
Pain & Pain Management (AREA)
Transplantation (AREA)
Endocrinology (AREA)
Biomedical Technology (AREA)
Ophthalmology & Optometry (AREA)
Neurosurgery (AREA)
Emergency Medicine (AREA)
Obesity (AREA)
Oncology (AREA)
Communicable Diseases (AREA)
Gastroenterology & Hepatology (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

SK1456-2001A 1999-04-14 2000-04-12 Substituované azoly, spôsob ich prípravy, farmaceutická kompozícia s ich obsahom a ich použitie SK14562001A3 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9908532.6A GB9908532D0 (en)	1999-04-14	1999-04-14	Organic compounds
GBGB9908531.8A GB9908531D0 (en)	1999-04-14	1999-04-14	Organic compounds
PCT/EP2000/003290 WO2000063204A2 (fr)	1999-04-14	2000-04-12	Azoles substitues

Publications (1)

Publication Number	Publication Date
SK14562001A3 true SK14562001A3 (sk)	2002-03-05

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ID=26315413

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1456-2001A SK14562001A3 (sk)	1999-04-14	2000-04-12	Substituované azoly, spôsob ich prípravy, farmaceutická kompozícia s ich obsahom a ich použitie

Country Status (25)

Country	Link
US (1)	US6579874B2 (fr)
EP (1)	EP1224180B1 (fr)
JP (1)	JP2003503311A (fr)
KR (1)	KR20010108504A (fr)
CN (1)	CN1378544A (fr)
AR (1)	AR023465A1 (fr)
AT (1)	ATE244236T1 (fr)
AU (1)	AU4295300A (fr)
BR (1)	BR0010598A (fr)
CA (1)	CA2370417A1 (fr)
CO (1)	CO5170501A1 (fr)
CZ (1)	CZ20013696A3 (fr)
DE (1)	DE60003709T2 (fr)
DK (1)	DK1224180T3 (fr)
ES (1)	ES2202114T3 (fr)
HU (1)	HUP0302747A2 (fr)
IL (1)	IL145836A0 (fr)
MX (1)	MXPA01010434A (fr)
NO (1)	NO20014987L (fr)
PE (1)	PE20010031A1 (fr)
PL (1)	PL364789A1 (fr)
PT (1)	PT1224180E (fr)
SK (1)	SK14562001A3 (fr)
TR (1)	TR200102967T2 (fr)
WO (1)	WO2000063204A2 (fr)

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PA8579601A1 (es)	2002-08-30	2004-05-07	Pfizer Prod Inc	Compuestos antiinflamatorios de di y trifloruro-triazolo-piridinas
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EP1992344A1 (fr)	2007-05-18	2008-11-19	Institut Curie	P38 alpha comme cible therapeutique pour les maladies associées á une mutation de FGFR3
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EP2113503A1 (fr)	2008-04-28	2009-11-04	Laboratorios Almirall, S.A.	Nouveaux dérivés d'indolin-2-one substitués et leur utilisation comme inhibiteurs de p38 mitogen-activated kinase
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2000
- 2000-04-11 CO CO00026470A patent/CO5170501A1/es not_active Application Discontinuation
- 2000-04-12 DK DK00922630T patent/DK1224180T3/da active
- 2000-04-12 PL PL00364789A patent/PL364789A1/xx not_active Application Discontinuation
- 2000-04-12 KR KR1020017013086A patent/KR20010108504A/ko not_active Withdrawn
- 2000-04-12 CZ CZ20013696A patent/CZ20013696A3/cs unknown
- 2000-04-12 AU AU42953/00A patent/AU4295300A/en not_active Abandoned
- 2000-04-12 PT PT00922630T patent/PT1224180E/pt unknown
- 2000-04-12 PE PE2000000337A patent/PE20010031A1/es not_active Application Discontinuation
- 2000-04-12 MX MXPA01010434A patent/MXPA01010434A/es unknown
- 2000-04-12 EP EP00922630A patent/EP1224180B1/fr not_active Expired - Lifetime
- 2000-04-12 JP JP2000612294A patent/JP2003503311A/ja active Pending
- 2000-04-12 AT AT00922630T patent/ATE244236T1/de not_active IP Right Cessation
- 2000-04-12 BR BR0010598-8A patent/BR0010598A/pt not_active IP Right Cessation
- 2000-04-12 TR TR2001/02967T patent/TR200102967T2/xx unknown
- 2000-04-12 WO PCT/EP2000/003290 patent/WO2000063204A2/fr not_active Ceased
- 2000-04-12 DE DE60003709T patent/DE60003709T2/de not_active Expired - Fee Related
- 2000-04-12 IL IL14583600A patent/IL145836A0/xx unknown
- 2000-04-12 HU HU0302747A patent/HUP0302747A2/hu unknown
- 2000-04-12 ES ES00922630T patent/ES2202114T3/es not_active Expired - Lifetime
- 2000-04-12 CA CA002370417A patent/CA2370417A1/fr not_active Abandoned
- 2000-04-12 CN CN00807552A patent/CN1378544A/zh active Pending
- 2000-04-12 SK SK1456-2001A patent/SK14562001A3/sk unknown
- 2000-04-12 AR ARP000101686A patent/AR023465A1/es unknown
2001
- 2001-10-12 US US09/975,913 patent/US6579874B2/en not_active Expired - Fee Related
- 2001-10-12 NO NO20014987A patent/NO20014987L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CZ20013696A3 (cs)	2002-02-13
BR0010598A (pt)	2002-02-05
WO2000063204A2 (fr)	2000-10-26
PT1224180E (pt)	2003-11-28
US6579874B2 (en)	2003-06-17
JP2003503311A (ja)	2003-01-28
AR023465A1 (es)	2002-09-04
NO20014987L (no)	2001-12-14
PE20010031A1 (es)	2001-02-23
US20020049220A1 (en)	2002-04-25
IL145836A0 (en)	2002-07-25
AU4295300A (en)	2000-11-02
DE60003709T2 (de)	2004-12-23
HUP0302747A2 (hu)	2003-12-29
MXPA01010434A (es)	2002-03-27
NO20014987D0 (no)	2001-10-12
DE60003709D1 (de)	2003-08-07
EP1224180B1 (fr)	2003-07-02
ES2202114T3 (es)	2004-04-01
DK1224180T3 (da)	2003-10-20
WO2000063204A3 (fr)	2002-05-23
ATE244236T1 (de)	2003-07-15
TR200102967T2 (tr)	2002-01-21
PL364789A1 (en)	2004-12-13
CO5170501A1 (es)	2002-06-27
EP1224180A2 (fr)	2002-07-24
KR20010108504A (ko)	2001-12-07
CA2370417A1 (fr)	2000-10-26
CN1378544A (zh)	2002-11-06

Publication	Publication Date	Title
SK14562001A3 (sk)	2002-03-05	Substituované azoly, spôsob ich prípravy, farmaceutická kompozícia s ich obsahom a ich použitie
US6608072B1 (en)	2003-08-19	Thiazole compounds and their pharmaceutical use
JP3704362B2 (ja)	2005-10-12	２−置換４，５−ジアリールイミダゾール
CN101505752B (zh)	2012-12-05	脯氨酸羟化酶抑制剂
DE69723104T2 (de)	2004-04-29	Piridin-2-yl-methylamin-derivate, verfahren zu deren herstellung und ihre verwendung als arzneimittel
WO2000026209A1 (fr)	2000-05-11	4-phenyl-5-pyrimidinyl-imidazoles anti-inflammatoires
US9453014B2 (en)	2016-09-27	Cyclic amide derivatives as inhibitors of 11-β-hydroxysteroid dehydrogenase and uses thereof
AU2017263361A1 (en)	2018-10-04	Cyclopropyl-amide compounds as dual LSD1/HDAC inhibitors
EP2668183A1 (fr)	2013-12-04	Inhibition de l'il17 et de l'ifn-gamma dans le traitement d'une inflammation autoimmune
SK279472B6 (sk)	1998-11-04	Fenoxy- a fenoxyalkylpiperidíny, farmaceutický pro
SK283461B6 (sk)	2003-08-05	Deriváty oxadiazolu a tiadiazolu, ich použitie, spôsob a medziprodukty na ich výrobu a farmaceutické kompozície na ich báze
WO2001032173A1 (fr)	2001-05-10	Inhibiteurs de neurocytotoxicite de l'acide kainique
WO2002022588A1 (fr)	2002-03-21	Nouveau derive de pyrimidine et nouveau derive de pyridine
EP0215250B1 (fr)	1992-12-30	1,4-Dihydropyridines substitués en position 2, leur procédé de préparation et compositions pharmaceutiques les contenant
ES2228884T3 (es)	2005-04-16	Nuevos derivados de imidazol.
US20210284658A1 (en)	2021-09-16	Novel thiazole derivatives and pharmaceutically acceptable salts thereof
CA2794676A1 (fr)	2011-10-06	Inhibiteurs de cytokine
JP3999861B2 (ja)	2007-10-31	新規ピリダジン誘導体及びこれを有効成分とする医薬
JPH11209344A (ja)	1999-08-03	含窒素複素環化合物
JP3739916B2 (ja)	2006-01-25	サイトカイン産生阻害剤
NZ626745B2 (en)	2016-09-27	Cyclic amide derivatives as inhibitors of 11 - beta - hydroxysteroid dehydrogenase and uses thereof
HK1063462A (en)	2004-12-31	4-imidazolin-2-one compounds