NO323766B1 - Azaindoler, farmasoytiske sammensetninger innbefattende og deres anvendelse for fremstilling av medikament - Google Patents
Azaindoler, farmasoytiske sammensetninger innbefattende og deres anvendelse for fremstilling av medikament Download PDFInfo
- Publication number
- NO323766B1 NO323766B1 NO20023032A NO20023032A NO323766B1 NO 323766 B1 NO323766 B1 NO 323766B1 NO 20023032 A NO20023032 A NO 20023032A NO 20023032 A NO20023032 A NO 20023032A NO 323766 B1 NO323766 B1 NO 323766B1
- Authority
- NO
- Norway
- Prior art keywords
- pyrrolo
- methyl
- compound according
- alkyl
- optionally substituted
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 453
- 239000000203 mixture Substances 0.000 claims description 158
- 125000000217 alkyl group Chemical group 0.000 claims description 125
- 229910052739 hydrogen Inorganic materials 0.000 claims description 92
- 239000001257 hydrogen Substances 0.000 claims description 91
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 86
- 150000003839 salts Chemical class 0.000 claims description 70
- -1 cyclic acetal Chemical class 0.000 claims description 67
- 125000001072 heteroaryl group Chemical group 0.000 claims description 63
- 229940002612 prodrug Drugs 0.000 claims description 62
- 239000000651 prodrug Substances 0.000 claims description 62
- 125000003118 aryl group Chemical group 0.000 claims description 56
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 52
- 239000002253 acid Substances 0.000 claims description 50
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 46
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 42
- 150000002148 esters Chemical class 0.000 claims description 41
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 36
- 150000002431 hydrogen Chemical class 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 35
- 239000012453 solvate Substances 0.000 claims description 33
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 31
- 125000005843 halogen group Chemical group 0.000 claims description 28
- 150000001204 N-oxides Chemical class 0.000 claims description 27
- 150000004677 hydrates Chemical class 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 108091000080 Phosphotransferase Proteins 0.000 claims description 22
- 102000020233 phosphotransferase Human genes 0.000 claims description 22
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 19
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 19
- 125000003107 substituted aryl group Chemical group 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 14
- 125000001475 halogen functional group Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 11
- 125000001041 indolyl group Chemical group 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 8
- 230000003197 catalytic effect Effects 0.000 claims description 8
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 6
- 206010003246 arthritis Diseases 0.000 claims description 6
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 125000000304 alkynyl group Chemical group 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 208000018937 joint inflammation Diseases 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- FTJGHPGHUSLQAK-UHFFFAOYSA-N 2-(5-methoxy-1-methylindol-3-yl)-1h-pyrrolo[2,3-b]pyridine-4-carbonitrile Chemical compound C1=CN=C2NC(C3=CN(C)C4=CC=C(C=C43)OC)=CC2=C1C#N FTJGHPGHUSLQAK-UHFFFAOYSA-N 0.000 claims description 3
- CNJGCQXKBAUFNA-UHFFFAOYSA-N 4-(3-methyl-1h-pyrrolo[2,3-b]pyridin-2-yl)benzoic acid Chemical compound N1C2=NC=CC=C2C(C)=C1C1=CC=C(C(O)=O)C=C1 CNJGCQXKBAUFNA-UHFFFAOYSA-N 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 3
- 150000002894 organic compounds Chemical class 0.000 claims description 3
- QBUASRVBPRBVRJ-UHFFFAOYSA-N 1-[1-methyl-3-(1h-pyrrolo[2,3-b]pyridin-2-yl)indol-5-yl]oxycyclobutane-1-carboxamide Chemical compound C=1C=C2N(C)C=C(C=3NC4=NC=CC=C4C=3)C2=CC=1OC1(C(N)=O)CCC1 QBUASRVBPRBVRJ-UHFFFAOYSA-N 0.000 claims description 2
- QOWCSDWRCIPYJJ-UHFFFAOYSA-N 2-(4-bromophenyl)-3-methyl-1h-pyrrolo[2,3-b]pyridine Chemical compound N1C2=NC=CC=C2C(C)=C1C1=CC=C(Br)C=C1 QOWCSDWRCIPYJJ-UHFFFAOYSA-N 0.000 claims description 2
- PAUWEYGKUDICMQ-UHFFFAOYSA-N 2-(4-chlorophenyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CC(Cl)=CC=C1C1=CC2=CC=CN=C2N1 PAUWEYGKUDICMQ-UHFFFAOYSA-N 0.000 claims description 2
- SHISXEDJQZVJAL-UHFFFAOYSA-N 2-(4-methoxyphenyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=CC2=CC=CN=C2N1 SHISXEDJQZVJAL-UHFFFAOYSA-N 0.000 claims description 2
- UNQRREMUTOUZSE-UHFFFAOYSA-N 2-(4-methoxyphenyl)-3-methyl-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CC(OC)=CC=C1C1=C(C)C2=CC=CN=C2N1 UNQRREMUTOUZSE-UHFFFAOYSA-N 0.000 claims description 2
- PPWLAQVKIFDULF-UHFFFAOYSA-N 2-phenyl-1h-pyrrolo[2,3-b]pyridine Chemical compound N1C2=NC=CC=C2C=C1C1=CC=CC=C1 PPWLAQVKIFDULF-UHFFFAOYSA-N 0.000 claims description 2
- ALSYTSCUTDAYIU-UHFFFAOYSA-N 2-pyridin-3-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound N1C2=NC=CC=C2C=C1C1=CC=CN=C1 ALSYTSCUTDAYIU-UHFFFAOYSA-N 0.000 claims description 2
- UGBJLTPTFVECSC-UHFFFAOYSA-N 3-methyl-2-phenyl-1h-pyrrolo[2,3-b]pyridine Chemical compound N1C2=NC=CC=C2C(C)=C1C1=CC=CC=C1 UGBJLTPTFVECSC-UHFFFAOYSA-N 0.000 claims description 2
- PPRZWBLCPANUPB-UHFFFAOYSA-N 4-methyl-2-phenyl-1h-pyrrolo[2,3-b]pyridine Chemical compound C=1C=2C(C)=CC=NC=2NC=1C1=CC=CC=C1 PPRZWBLCPANUPB-UHFFFAOYSA-N 0.000 claims description 2
- LQAFCJAXORNEHL-UHFFFAOYSA-N 5-methyl-2-phenyl-1h-pyrrolo[2,3-b]pyridine Chemical compound C=1C2=CC(C)=CN=C2NC=1C1=CC=CC=C1 LQAFCJAXORNEHL-UHFFFAOYSA-N 0.000 claims description 2
- 229910014033 C-OH Inorganic materials 0.000 claims description 2
- 229910014570 C—OH Inorganic materials 0.000 claims description 2
- UVPSSGJTBLNVRE-UHFFFAOYSA-N Moniliformin Natural products O=C1C(OC)=CC(=O)C=2C1=C1C(=O)C(OC)=CC(=O)C1=CC=2 UVPSSGJTBLNVRE-UHFFFAOYSA-N 0.000 claims description 2
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000004442 acylamino group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000003435 aroyl group Chemical group 0.000 claims description 2
- 125000005239 aroylamino group Chemical group 0.000 claims description 2
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 2
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 2
- 125000005135 aryl sulfinyl group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- 125000005110 aryl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 125000005114 heteroarylalkoxy group Chemical group 0.000 claims description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 2
- 208000027866 inflammatory disease Diseases 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- KGPQKNJSZNXOPV-UHFFFAOYSA-N moniliformin Chemical compound OC1=CC(=O)C1=O KGPQKNJSZNXOPV-UHFFFAOYSA-N 0.000 claims description 2
- 125000003226 pyrazolyl 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
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 101100256910 Drosophila melanogaster sick gene Proteins 0.000 claims 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- UPAYIGZHWMYXCV-UHFFFAOYSA-N 3-methyl-2-(4-methylphenyl)-1h-pyrrolo[2,3-b]pyridine Chemical compound N1C2=NC=CC=C2C(C)=C1C1=CC=C(C)C=C1 UPAYIGZHWMYXCV-UHFFFAOYSA-N 0.000 claims 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims 1
- QCMDUUAPARGBIF-UHFFFAOYSA-N methyl 4-(3-methyl-1h-pyrrolo[2,3-b]pyridin-2-yl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1C1=C(C)C2=CC=CN=C2N1 QCMDUUAPARGBIF-UHFFFAOYSA-N 0.000 claims 1
- ITJRVXVDBRQCJG-UHFFFAOYSA-N propan-2-yl 4-(3-methyl-1h-pyrrolo[2,3-b]pyridin-2-yl)benzoate Chemical compound C1=CC(C(=O)OC(C)C)=CC=C1C1=C(C)C2=CC=CN=C2N1 ITJRVXVDBRQCJG-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 406
- 239000007787 solid Substances 0.000 description 319
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 198
- 239000000243 solution Substances 0.000 description 195
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 155
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 146
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 124
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 123
- 238000002844 melting Methods 0.000 description 105
- 230000008018 melting Effects 0.000 description 105
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 95
- 238000000034 method Methods 0.000 description 92
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- 238000005481 NMR spectroscopy Methods 0.000 description 63
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 53
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 52
- IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 47
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- 238000003756 stirring Methods 0.000 description 45
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- 238000004809 thin layer chromatography Methods 0.000 description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 37
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- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 9
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- ZXUCBXRTRRIBSO-UHFFFAOYSA-L tetrabutylazanium;sulfate Chemical compound [O-]S([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC ZXUCBXRTRRIBSO-UHFFFAOYSA-L 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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GBGB9930698.7A GB9930698D0 (en) | 1999-12-24 | 1999-12-24 | Chemical compounds |
US21581800P | 2000-07-05 | 2000-07-05 | |
PCT/GB2000/004993 WO2001047922A2 (en) | 1999-12-24 | 2000-12-27 | Azaindoles |
Publications (3)
Publication Number | Publication Date |
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NO20023032L NO20023032L (no) | 2002-06-21 |
NO20023032D0 NO20023032D0 (no) | 2002-06-21 |
NO323766B1 true NO323766B1 (no) | 2007-07-02 |
Family
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Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20023032A NO323766B1 (no) | 1999-12-24 | 2002-06-21 | Azaindoler, farmasoytiske sammensetninger innbefattende og deres anvendelse for fremstilling av medikament |
NO20066017A NO330747B1 (no) | 1999-12-24 | 2006-12-27 | Farmasoytiske sammensetninger omfattende azaindoler, forbindelser som er azaindoler samt anvendelse derav. |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20066017A NO330747B1 (no) | 1999-12-24 | 2006-12-27 | Farmasoytiske sammensetninger omfattende azaindoler, forbindelser som er azaindoler samt anvendelse derav. |
Country Status (27)
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US (2) | US6770643B2 (bg) |
EP (2) | EP1990343B1 (bg) |
JP (1) | JP5436507B2 (bg) |
KR (2) | KR100910488B1 (bg) |
CN (2) | CN100379734C (bg) |
AP (2) | AP1587A (bg) |
AU (1) | AU777717B2 (bg) |
BG (2) | BG66066B1 (bg) |
BR (1) | BR0017038A (bg) |
CA (2) | CA2395593C (bg) |
CY (1) | CY1110951T1 (bg) |
CZ (2) | CZ301751B6 (bg) |
DZ (1) | DZ3377A1 (bg) |
EA (1) | EA005212B1 (bg) |
EE (1) | EE05180B1 (bg) |
HK (1) | HK1050191B (bg) |
HR (1) | HRP20020547B1 (bg) |
HU (1) | HUP0203895A3 (bg) |
IL (3) | IL150388A0 (bg) |
MA (1) | MA26857A1 (bg) |
MX (1) | MXPA02006338A (bg) |
NO (2) | NO323766B1 (bg) |
NZ (1) | NZ519121A (bg) |
OA (1) | OA12514A (bg) |
PL (1) | PL209572B1 (bg) |
SK (2) | SK288019B6 (bg) |
WO (1) | WO2001047922A2 (bg) |
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