OA12514A - Azaindoles. - Google Patents

Azaindoles. Download PDF

Info

Publication number: OA12514A
Authority: OA; OAPI
Prior art keywords: compound according; daims; alkyl; aryl; hydrogen
Prior art date: 1999-12-24

Application number

OA1200200199A

Other languages

English (en)

Inventor

Shelley Amendola

Paul Joseph Cox

Stephanie Deprets

Chris Adlin

Justine Yeun Quai Lai

Tahir Nadeem Majid

Andrew David Morley

Original Assignee

Aventis Pharma Ltd

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.)

1999-12-24

Filing date

2000-12-27

Publication date

2006-05-29

1999-12-24 Priority claimed from GBGB9930698.7A external-priority patent/GB9930698D0/en

2000-12-27 Application filed by Aventis Pharma Ltd filed Critical Aventis Pharma Ltd

2006-05-29 Publication of OA12514A publication Critical patent/OA12514A/en

Links

125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 title description 10
150000001875 compounds Chemical class 0.000 claims abstract description 452
239000000203 mixture Substances 0.000 claims abstract description 157
125000000217 alkyl group Chemical group 0.000 claims abstract description 120
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 90
239000001257 hydrogen Substances 0.000 claims abstract description 88
229940002612 prodrug Drugs 0.000 claims abstract description 60
239000000651 prodrug Substances 0.000 claims abstract description 60
125000001072 heteroaryl group Chemical group 0.000 claims abstract description 59
125000003118 aryl group Chemical group 0.000 claims abstract description 55
150000003839 salts Chemical class 0.000 claims abstract description 47
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 42
125000005843 halogen group Chemical group 0.000 claims abstract description 31
125000003342 alkenyl group Chemical group 0.000 claims abstract description 26
125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 17
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 17
125000001475 halogen functional group Chemical group 0.000 claims abstract description 16
125000001424 substituent group Chemical group 0.000 claims abstract description 7
125000002252 acyl group Chemical group 0.000 claims abstract description 6
229910014033 C-OH Inorganic materials 0.000 claims abstract description 4
229910014570 C—OH Inorganic materials 0.000 claims abstract description 4
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 82
-1 cyclic acetal Chemical class 0.000 claims description 75
239000002253 acid Substances 0.000 claims description 71
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 65
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 41
KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 40
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 36
150000002431 hydrogen Chemical class 0.000 claims description 36
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 32
238000011282 treatment Methods 0.000 claims description 32
230000000694 effects Effects 0.000 claims description 30
125000000753 cycloalkyl group Chemical group 0.000 claims description 28
150000001204 N-oxides Chemical class 0.000 claims description 23
150000004677 hydrates Chemical class 0.000 claims description 23
125000003545 alkoxy group Chemical group 0.000 claims description 22
BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 claims description 21
108091000080 Phosphotransferase Proteins 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
102000020233 phosphotransferase Human genes 0.000 claims description 20
PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 19
125000003107 substituted aryl group Chemical group 0.000 claims description 18
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 15
125000003710 aryl alkyl group Chemical group 0.000 claims description 14
206010028980 Neoplasm Diseases 0.000 claims description 12
125000001041 indolyl group Chemical group 0.000 claims description 12
230000002401 inhibitory effect Effects 0.000 claims description 12
102000000551 Syk Kinase Human genes 0.000 claims description 10
108010016672 Syk Kinase Proteins 0.000 claims description 10
125000006414 CCl Chemical group ClC* 0.000 claims description 9
125000005530 alkylenedioxy group Chemical group 0.000 claims description 9
229910052736 halogen Inorganic materials 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
125000000168 pyrrolyl group Chemical group 0.000 claims description 9
125000003302 alkenyloxy group Chemical group 0.000 claims description 8
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 8
125000003831 tetrazolyl group Chemical group 0.000 claims description 8
230000003197 catalytic effect Effects 0.000 claims description 7
150000002367 halogens Chemical group 0.000 claims description 7
238000002560 therapeutic procedure Methods 0.000 claims description 7
206010003246 arthritis Diseases 0.000 claims description 6
125000004076 pyridyl group Chemical group 0.000 claims description 6
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 5
125000000304 alkynyl group Chemical group 0.000 claims description 5
230000001668 ameliorated effect Effects 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
201000004681 Psoriasis Diseases 0.000 claims description 4
201000011510 cancer Diseases 0.000 claims description 4
125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
239000003112 inhibitor Substances 0.000 claims description 4
208000018937 joint inflammation Diseases 0.000 claims description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
208000006673 asthma Diseases 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 claims description 3
239000005711 Benzoic acid Substances 0.000 claims description 2
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
239000000969 carrier Substances 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
125000003226 pyrazolyl group Chemical group 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 4
238000004519 manufacturing process Methods 0.000 claims 1
150000004702 methyl esters Chemical class 0.000 claims 1
102000001253 Protein Kinase Human genes 0.000 abstract description 8
108060006633 protein kinase Proteins 0.000 abstract description 8
239000012453 solvate Substances 0.000 abstract description 2
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 365
239000007787 solid Substances 0.000 description 301
239000000243 solution Substances 0.000 description 183
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 171
OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Substances OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 128
229940093499 ethyl acetate Drugs 0.000 description 121
235000019439 ethyl acetate Nutrition 0.000 description 121
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 111
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 102
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 83
238000000034 method Methods 0.000 description 75
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 70
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 64
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 61
238000004128 high performance liquid chromatography Methods 0.000 description 61
210000004027 cell Anatomy 0.000 description 59
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 58
239000011541 reaction mixture Substances 0.000 description 58
238000006243 chemical reaction Methods 0.000 description 56
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
238000003756 stirring Methods 0.000 description 53
IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 41
238000004809 thin layer chromatography Methods 0.000 description 41
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 38
239000000377 silicon dioxide Substances 0.000 description 38
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 35
229910052757 nitrogen Inorganic materials 0.000 description 34
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 33
210000004072 lung Anatomy 0.000 description 33
238000003818 flash chromatography Methods 0.000 description 32
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 31
239000000427 antigen Substances 0.000 description 31
108091007433 antigens Proteins 0.000 description 31
102000036639 antigens Human genes 0.000 description 31
238000010992 reflux Methods 0.000 description 31
239000012442 inert solvent Substances 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
239000012267 brine Substances 0.000 description 27
230000000875 corresponding effect Effects 0.000 description 27
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 27
YTWCODZNNZBQFV-KBXCAEBGSA-N (1R,2R)-2-[[4-(2-fluoro-5-propan-2-yloxyphenyl)phenoxy]methyl]cyclopropane-1-carboxylic acid Chemical compound FC1=C(C=C(C=C1)OC(C)C)C1=CC=C(C=C1)OC[C@H]1[C@@H](C1)C(=O)O YTWCODZNNZBQFV-KBXCAEBGSA-N 0.000 description 26
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical class CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
229910052799 carbon Inorganic materials 0.000 description 26
239000003921 oil Substances 0.000 description 25
235000019198 oils Nutrition 0.000 description 25
239000012634 fragment Substances 0.000 description 24
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
230000005764 inhibitory process Effects 0.000 description 21
229910052938 sodium sulfate Inorganic materials 0.000 description 21
235000011152 sodium sulphate Nutrition 0.000 description 21
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 20
150000001721 carbon Chemical group 0.000 description 20
229960003010 sodium sulfate Drugs 0.000 description 20
108010058846 Ovalbumin Proteins 0.000 description 19
239000000284 extract Substances 0.000 description 19
229940092253 ovalbumin Drugs 0.000 description 19
239000002904 solvent Substances 0.000 description 19
239000002585 base Substances 0.000 description 18
229940079593 drug Drugs 0.000 description 18
239000003814 drug Substances 0.000 description 18
239000000725 suspension Substances 0.000 description 18
230000008569 process Effects 0.000 description 17
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
241000700159 Rattus Species 0.000 description 16
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 15
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 15
108090000461 Aurora Kinase A Proteins 0.000 description 14
102100032311 Aurora kinase A Human genes 0.000 description 14
LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
125000004432 carbon atom Chemical group C* 0.000 description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
230000004044 response Effects 0.000 description 14
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
102000016621 Focal Adhesion Protein-Tyrosine Kinases Human genes 0.000 description 13
108010067715 Focal Adhesion Protein-Tyrosine Kinases Proteins 0.000 description 13
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
229960000583 acetic acid Drugs 0.000 description 13
238000003556 assay Methods 0.000 description 13
125000004429 atom Chemical group 0.000 description 13
239000010410 layer Substances 0.000 description 13
238000000746 purification Methods 0.000 description 13
210000001519 tissue Anatomy 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 12
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
150000002148 esters Chemical class 0.000 description 12
235000019260 propionic acid Nutrition 0.000 description 12
239000012312 sodium hydride Substances 0.000 description 12
229910000104 sodium hydride Inorganic materials 0.000 description 12
230000006978 adaptation Effects 0.000 description 11
239000006071 cream Substances 0.000 description 11
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 11
238000005304 joining Methods 0.000 description 11
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 11
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 10
108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 10
102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
238000012360 testing method Methods 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 9
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 9
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 9
239000003513 alkali Substances 0.000 description 9
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 9
238000000921 elemental analysis Methods 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
239000012458 free base Substances 0.000 description 9
239000002609 medium Substances 0.000 description 9
ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 8
206010020751 Hypersensitivity Diseases 0.000 description 8
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
229920005654 Sephadex Polymers 0.000 description 8
239000012507 Sephadex™ Substances 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
230000029936 alkylation Effects 0.000 description 8
238000005804 alkylation reaction Methods 0.000 description 8
230000007815 allergy Effects 0.000 description 8
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 8
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
229910052794 bromium Inorganic materials 0.000 description 8
238000011685 brown norway rat Methods 0.000 description 8
239000006185 dispersion Substances 0.000 description 8
238000001914 filtration Methods 0.000 description 8
CAWHJQAVHZEVTJ-UHFFFAOYSA-N methylpyrazine Chemical compound CC1=CN=CC=N1 CAWHJQAVHZEVTJ-UHFFFAOYSA-N 0.000 description 8
239000003960 organic solvent Substances 0.000 description 8
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 7
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
101150041968 CDC13 gene Proteins 0.000 description 7
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 7
239000000872 buffer Substances 0.000 description 7
235000019253 formic acid Nutrition 0.000 description 7
230000014509 gene expression Effects 0.000 description 7
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 7
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 7
210000000440 neutrophil Anatomy 0.000 description 7
229910000027 potassium carbonate Inorganic materials 0.000 description 7
239000000047 product Substances 0.000 description 7
239000000758 substrate Substances 0.000 description 7
229940104230 thymidine Drugs 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
206010070834 Sensitisation Diseases 0.000 description 6
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
239000003054 catalyst Substances 0.000 description 6
231100000673 dose–response relationship Toxicity 0.000 description 6
KVFIJIWMDBAGDP-UHFFFAOYSA-N ethylpyrazine Chemical compound CCC1=CN=CC=N1 KVFIJIWMDBAGDP-UHFFFAOYSA-N 0.000 description 6
210000003630 histaminocyte Anatomy 0.000 description 6
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125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
241000701447 unidentified baculovirus Species 0.000 description 1
238000011144 upstream manufacturing Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000013598 vector Substances 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
230000035899 viability Effects 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
229910021511 zinc hydroxide Inorganic materials 0.000 description 1
229940007718 zinc hydroxide Drugs 0.000 description 1

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- 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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- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- 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

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Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Immunology (AREA)
Pulmonology (AREA)
Epidemiology (AREA)
Rheumatology (AREA)
Diabetes (AREA)
Neurosurgery (AREA)
Hematology (AREA)
Neurology (AREA)
Physical Education & Sports Medicine (AREA)
Vascular Medicine (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Biomedical Technology (AREA)
Pain & Pain Management (AREA)
Emergency Medicine (AREA)
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Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Obesity (AREA)
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Orthopedic Medicine & Surgery (AREA)
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OA1200200199A 1999-12-24 2000-12-27 Azaindoles. OA12514A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GBGB9930698.7A GB9930698D0 (en)	1999-12-24	1999-12-24	Chemical compounds
US21581800P	2000-07-05	2000-07-05
PCT/GB2000/004993 WO2001047922A2 (fr)	1999-12-24	2000-12-27	Azaindoles

Publications (1)

Publication Number	Publication Date
OA12514A true OA12514A (en)	2006-05-29

Family

ID=26316153

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200200199A OA12514A (en)	1999-12-24	2000-12-27	Azaindoles.

Country Status (27)

Country	Link
US (2)	US6770643B2 (fr)
EP (2)	EP1990343B1 (fr)
JP (1)	JP5436507B2 (fr)
KR (2)	KR100755622B1 (fr)
CN (2)	CN100379734C (fr)
AP (2)	AP1917A (fr)
AU (1)	AU777717B2 (fr)
BG (2)	BG66066B1 (fr)
BR (1)	BR0017038A (fr)
CA (2)	CA2395593C (fr)
CY (1)	CY1110951T1 (fr)
CZ (2)	CZ301751B6 (fr)
DZ (1)	DZ3377A1 (fr)
EA (1)	EA005212B1 (fr)
EE (1)	EE05180B1 (fr)
HK (1)	HK1050191B (fr)
HR (1)	HRP20020547B1 (fr)
HU (1)	HUP0203895A3 (fr)
IL (3)	IL150388A0 (fr)
MA (1)	MA26857A1 (fr)
MX (1)	MXPA02006338A (fr)
NO (2)	NO323766B1 (fr)
NZ (1)	NZ519121A (fr)
OA (1)	OA12514A (fr)
PL (1)	PL209572B1 (fr)
SK (2)	SK287882B6 (fr)
WO (1)	WO2001047922A2 (fr)

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- 2008-08-21 IL IL193615A patent/IL193615A0/en unknown
2010
- 2010-03-18 BG BG10110623A patent/BG66176B1/bg unknown
- 2010-11-25 CY CY20101101074T patent/CY1110951T1/el unknown
2011
- 2011-09-08 JP JP2011195789A patent/JP5436507B2/ja not_active Expired - Fee Related

Also Published As

Publication number	Publication date
AU2209401A (en)	2001-07-09
AP1917A (en)	2008-11-12
KR100910488B1 (ko)	2009-08-04
SK9012002A3 (en)	2003-04-01
NO323766B1 (no)	2007-07-02
AP2002002516A0 (en)	2002-06-30
IL150388A0 (en)	2002-12-01
PL209572B1 (pl)	2011-09-30
DZ3377A1 (fr)	2001-07-05
IL193615A0 (en)	2009-05-04
AU777717B2 (en)	2004-10-28
EP1263759B1 (fr)	2010-09-08
SK287882B6 (sk)	2012-02-03
NO330747B1 (no)	2011-07-04
CZ20022207A3 (cs)	2002-11-13
CA2699568A1 (fr)	2001-07-05
CY1110951T1 (el)	2015-06-11
NZ519121A (en)	2004-05-28
US20040198737A1 (en)	2004-10-07
MA26857A1 (fr)	2004-12-20
CA2395593A1 (fr)	2001-07-05
KR20070050103A (ko)	2007-05-14
IL150388A (en)	2010-11-30
JP5436507B2 (ja)	2014-03-05
CZ301750B6 (cs)	2010-06-09
BR0017038A (pt)	2003-01-07
JP2012031181A (ja)	2012-02-16
EP1990343B1 (fr)	2012-04-04
CN100379734C (zh)	2008-04-09
CZ301751B6 (cs)	2010-06-09
KR20020062663A (ko)	2002-07-26
HRP20020547B1 (hr)	2011-06-30
US7227020B2 (en)	2007-06-05
US20040009983A1 (en)	2004-01-15
BG66066B1 (bg)	2011-01-31
PL355819A1 (en)	2004-05-17
BG106836A (bg)	2003-04-30
EE200200343A (et)	2003-06-16
HUP0203895A3 (en)	2004-09-28
HUP0203895A2 (hu)	2003-02-28
NO20066017L (no)	2002-06-21
US6770643B2 (en)	2004-08-03
NO20023032D0 (no)	2002-06-21
AP2006003492A0 (en)	2006-02-28
WO2001047922A2 (fr)	2001-07-05
EP1263759A2 (fr)	2002-12-11
HRP20020547A2 (hr)	2005-10-31
CA2699568C (fr)	2013-03-12
NO20023032L (no)	2002-06-21
MXPA02006338A (es)	2002-12-13
AP1587A (en)	2006-03-02
EP1990343A2 (fr)	2008-11-12
EP1990343A3 (fr)	2008-12-10
HK1050191B (en)	2011-04-29
KR100755622B1 (ko)	2007-09-04
HK1050191A1 (en)	2003-06-13
EA200200707A1 (ru)	2003-02-27
EA005212B1 (ru)	2004-12-30
CN1615873A (zh)	2005-05-18
CN1413213A (zh)	2003-04-23
BG66176B1 (bg)	2011-11-30
BG110623A (bg)	2010-07-30
WO2001047922A3 (fr)	2002-01-17
SK288019B6 (sk)	2012-11-05
EE05180B1 (et)	2009-06-15
CA2395593C (fr)	2011-08-02