NO318383B1 - Derivater av 2-aminopyridiner, anvendelse av dem som medikamenter og farmasoytiske preparater inneholdende dem - Google Patents

Derivater av 2-aminopyridiner, anvendelse av dem som medikamenter og farmasoytiske preparater inneholdende dem Download PDF

Info

Publication number: NO318383B1
Authority: NO; Norway
Prior art keywords: amino; methyl; hydrochloride; residue; pyridinyl
Prior art date: 1998-07-08

Application number

NO20010031A

Other languages

English (en)

Norwegian (no)

Other versions

NO20010031L (no

NO20010031D0 (no

Inventor

De Lassauniere Pierre Chabrier

Jerry Harnett

Serge Auvin

Dominique Pons

Dennis C H Bigg

Gerard Ulibarri

Original Assignee

Sod Conseils Rech Applic

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.)

1998-07-08

Filing date

2001-01-03

Publication date

2005-03-14

1998-07-08 Priority claimed from FR9808732A external-priority patent/FR2780971B1/fr

1999-04-02 Priority claimed from FR9904133A external-priority patent/FR2791674A1/fr

2001-01-03 Application filed by Sod Conseils Rech Applic filed Critical Sod Conseils Rech Applic

2001-01-03 Publication of NO20010031D0 publication Critical patent/NO20010031D0/no

2001-01-05 Publication of NO20010031L publication Critical patent/NO20010031L/no

2005-03-14 Publication of NO318383B1 publication Critical patent/NO318383B1/no

Links

239000003814 drug Substances 0.000 title claims description 10
239000000825 pharmaceutical preparation Substances 0.000 title claims description 8
229940079593 drug Drugs 0.000 title claims description 4
150000003930 2-aminopyridines Chemical class 0.000 title abstract description 6
102000008299 Nitric Oxide Synthase Human genes 0.000 claims abstract description 12
108010021487 Nitric Oxide Synthase Proteins 0.000 claims abstract description 12
238000002360 preparation method Methods 0.000 claims abstract description 8
150000001875 compounds Chemical class 0.000 claims description 55
-1 methylenedioxy ring Chemical group 0.000 claims description 54
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 46
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 42
125000004432 carbon atom Chemical group C* 0.000 claims description 34
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
150000003839 salts Chemical class 0.000 claims description 33
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
125000000217 alkyl group Chemical group 0.000 claims description 22
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 18
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 15
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 14
229910052736 halogen Inorganic materials 0.000 claims description 13
125000003342 alkenyl group Chemical group 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 10
125000003545 alkoxy group Chemical group 0.000 claims description 10
230000002401 inhibitory effect Effects 0.000 claims description 10
125000004193 piperazinyl group Chemical group 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 9
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
230000003859 lipid peroxidation Effects 0.000 claims description 8
125000000304 alkynyl group Chemical group 0.000 claims description 7
METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 6
125000002947 alkylene group Chemical group 0.000 claims description 5
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 4
125000005843 halogen group Chemical group 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
150000001732 carboxylic acid derivatives Chemical group 0.000 claims 2
150000003254 radicals Chemical class 0.000 claims 2
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 1
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 1
239000004480 active ingredient Substances 0.000 claims 1
IRGUYZYDZVJINS-WLHGVMLRSA-N n-[4-(6-amino-4-methylpyridin-2-yl)butyl]-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxamide;(e)-but-2-enedioic acid Chemical compound OC(=O)\C=C\C(O)=O.CC1=CC(N)=NC(CCCCNC(=O)C2(C)OC3=C(C)C(C)=C(O)C(C)=C3CC2)=C1 IRGUYZYDZVJINS-WLHGVMLRSA-N 0.000 claims 1
238000000034 method Methods 0.000 abstract description 17
230000000694 effects Effects 0.000 abstract description 10
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 abstract description 4
239000003112 inhibitor Substances 0.000 abstract description 4
230000001225 therapeutic effect Effects 0.000 abstract description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 2
239000001301 oxygen Substances 0.000 abstract 2
229910052760 oxygen Inorganic materials 0.000 abstract 2
239000008194 pharmaceutical composition Substances 0.000 abstract 1
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 189
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 117
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 92
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 81
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 80
239000000543 intermediate Substances 0.000 description 74
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
239000000243 solution Substances 0.000 description 48
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
238000002844 melting Methods 0.000 description 34
230000008018 melting Effects 0.000 description 34
239000007787 solid Substances 0.000 description 30
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 28
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
IZZIWIAOVZOBLF-UHFFFAOYSA-N 5-methoxysalicylic acid Chemical compound COC1=CC=C(O)C(C(O)=O)=C1 IZZIWIAOVZOBLF-UHFFFAOYSA-N 0.000 description 24
150000001412 amines Chemical class 0.000 description 23
239000000047 product Substances 0.000 description 23
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
239000000843 powder Substances 0.000 description 22
239000003480 eluent Substances 0.000 description 21
239000011541 reaction mixture Substances 0.000 description 20
229910052938 sodium sulfate Inorganic materials 0.000 description 20
235000011152 sodium sulphate Nutrition 0.000 description 20
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
239000000377 silicon dioxide Substances 0.000 description 18
150000001408 amides Chemical class 0.000 description 16
238000003756 stirring Methods 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
238000001704 evaporation Methods 0.000 description 15
230000008020 evaporation Effects 0.000 description 15
239000000203 mixture Substances 0.000 description 14
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical class [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 13
239000003921 oil Substances 0.000 description 13
235000019198 oils Nutrition 0.000 description 13
239000012074 organic phase Substances 0.000 description 13
AAUQLHHARJUJEH-UHFFFAOYSA-N 2-hydroxy-5-methoxybenzoic acid Natural products COC1=CC=CC(O)=C1C(O)=O AAUQLHHARJUJEH-UHFFFAOYSA-N 0.000 description 12
238000009833 condensation Methods 0.000 description 12
230000005494 condensation Effects 0.000 description 12
238000011282 treatment Methods 0.000 description 12
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 11
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
238000003786 synthesis reaction Methods 0.000 description 11
GLEVLJDDWXEYCO-UHFFFAOYSA-N Trolox Chemical compound O1C(C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-UHFFFAOYSA-N 0.000 description 10
239000007864 aqueous solution Substances 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
238000010908 decantation Methods 0.000 description 9
239000012458 free base Substances 0.000 description 9
150000001299 aldehydes Chemical group 0.000 description 8
239000003642 reactive oxygen metabolite Substances 0.000 description 8
MNDTVJMRXYKBPV-UHFFFAOYSA-N 4-amino-2,6-ditert-butylphenol Chemical compound CC(C)(C)C1=CC(N)=CC(C(C)(C)C)=C1O MNDTVJMRXYKBPV-UHFFFAOYSA-N 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
150000001735 carboxylic acids Chemical class 0.000 description 6
238000006243 chemical reaction Methods 0.000 description 6
239000012230 colorless oil Substances 0.000 description 6
238000010511 deprotection reaction Methods 0.000 description 6
239000012429 reaction media Substances 0.000 description 6
239000012047 saturated solution Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 5
150000001298 alcohols Chemical class 0.000 description 5
239000002585 base Substances 0.000 description 5
DKZBBWMURDFHNE-NSCUHMNNSA-N coniferyl aldehyde Chemical compound COC1=CC(\C=C\C=O)=CC=C1O DKZBBWMURDFHNE-NSCUHMNNSA-N 0.000 description 5
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
229940118019 malondialdehyde Drugs 0.000 description 5
DKZBBWMURDFHNE-UHFFFAOYSA-N trans-coniferylaldehyde Natural products COC1=CC(C=CC=O)=CC=C1O DKZBBWMURDFHNE-UHFFFAOYSA-N 0.000 description 5
VGXWRKFUIOSXDW-UHFFFAOYSA-N 2-(2,5-dimethylpyrrol-1-yl)-4,6-dimethylpyridine Chemical compound CC1=CC=C(C)N1C1=CC(C)=CC(C)=N1 VGXWRKFUIOSXDW-UHFFFAOYSA-N 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 4
DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 4
BZORFPDSXLZWJF-UHFFFAOYSA-N N,N-dimethyl-1,4-phenylenediamine Chemical compound CN(C)C1=CC=C(N)C=C1 BZORFPDSXLZWJF-UHFFFAOYSA-N 0.000 description 4
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
125000003118 aryl group Chemical group 0.000 description 4
239000012267 brine Substances 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
238000001035 drying Methods 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
FCGKUUOTWLWJHE-UHFFFAOYSA-N 2,6-ditert-butyl-4-nitrophenol Chemical compound CC(C)(C)C1=CC([N+]([O-])=O)=CC(C(C)(C)C)=C1O FCGKUUOTWLWJHE-UHFFFAOYSA-N 0.000 description 3
QFXXARKSLAKVRL-UHFFFAOYSA-N 2-(3-chloropropoxy)oxane Chemical compound ClCCCOC1CCCCO1 QFXXARKSLAKVRL-UHFFFAOYSA-N 0.000 description 3
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 3
BRBUBVKGJRPRRD-UHFFFAOYSA-N 4,6-dimethylpyridin-2-amine Chemical compound CC1=CC(C)=NC(N)=C1 BRBUBVKGJRPRRD-UHFFFAOYSA-N 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
239000007995 HEPES buffer Substances 0.000 description 3
ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 3
229930064664 L-arginine Natural products 0.000 description 3
235000014852 L-arginine Nutrition 0.000 description 3
229930040373 Paraformaldehyde Natural products 0.000 description 3
241000700159 Rattus Species 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
230000002378 acidificating effect Effects 0.000 description 3
235000019270 ammonium chloride Nutrition 0.000 description 3
239000012300 argon atmosphere Substances 0.000 description 3
125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 description 3
239000000872 buffer Substances 0.000 description 3
150000003857 carboxamides Chemical class 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
210000003710 cerebral cortex Anatomy 0.000 description 3
206010008118 cerebral infarction Diseases 0.000 description 3
208000035475 disorder Diseases 0.000 description 3
238000001914 filtration Methods 0.000 description 3
239000006260 foam Substances 0.000 description 3
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 description 3
AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 3
229920002866 paraformaldehyde Polymers 0.000 description 3
230000007170 pathology Effects 0.000 description 3
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 3
238000010992 reflux Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
239000000126 substance Substances 0.000 description 3
239000000725 suspension Substances 0.000 description 3
125000004747 1,1-dimethylethoxycarbonyl group Chemical group CC(C)(OC(=O)*)C 0.000 description 2
YHYKLKNNBYLTQY-UHFFFAOYSA-N 1,1-diphenylhydrazine Chemical class C=1C=CC=CC=1N(N)C1=CC=CC=C1 YHYKLKNNBYLTQY-UHFFFAOYSA-N 0.000 description 2
ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 2
WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 2
AKEUNCKRJATALU-UHFFFAOYSA-N 2,6-dihydroxybenzoic acid Chemical compound OC(=O)C1=C(O)C=CC=C1O AKEUNCKRJATALU-UHFFFAOYSA-N 0.000 description 2
YSUIQYOGTINQIN-UZFYAQMZSA-N 2-amino-9-[(1S,6R,8R,9S,10R,15R,17R,18R)-8-(6-aminopurin-9-yl)-9,18-difluoro-3,12-dihydroxy-3,12-bis(sulfanylidene)-2,4,7,11,13,16-hexaoxa-3lambda5,12lambda5-diphosphatricyclo[13.2.1.06,10]octadecan-17-yl]-1H-purin-6-one Chemical compound NC1=NC2=C(N=CN2[C@@H]2O[C@@H]3COP(S)(=O)O[C@@H]4[C@@H](COP(S)(=O)O[C@@H]2[C@@H]3F)O[C@H]([C@H]4F)N2C=NC3=C2N=CN=C3N)C(=O)N1 YSUIQYOGTINQIN-UZFYAQMZSA-N 0.000 description 2
QFQYZMGOKIROEC-UHFFFAOYSA-N 3-(1,3-benzodioxol-5-yl)prop-2-enoic acid Chemical compound OC(=O)C=CC1=CC=C2OCOC2=C1 QFQYZMGOKIROEC-UHFFFAOYSA-N 0.000 description 2
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
OEVGRWSCCICFQA-UHFFFAOYSA-N 4-bromo-2,2,3-trimethylbutanoic acid Chemical compound BrCC(C)C(C)(C)C(O)=O OEVGRWSCCICFQA-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
DYFWWZPZBQTLBC-UHFFFAOYSA-N 5-amino-n-[4-(6-amino-4-methylpyridin-2-yl)butyl]-2-hydroxybenzamide;hydrochloride Chemical compound Cl.CC1=CC(N)=NC(CCCCNC(=O)C=2C(=CC=C(N)C=2)O)=C1 DYFWWZPZBQTLBC-UHFFFAOYSA-N 0.000 description 2
WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 description 2
FZHSPPYCNDYIKD-UHFFFAOYSA-N 5-methoxysalicylaldehyde Chemical compound COC1=CC=C(O)C(C=O)=C1 FZHSPPYCNDYIKD-UHFFFAOYSA-N 0.000 description 2
BKLJUYPLUWUEOQ-UHFFFAOYSA-N 6-bromopyridin-2-amine Chemical compound NC1=CC=CC(Br)=N1 BKLJUYPLUWUEOQ-UHFFFAOYSA-N 0.000 description 2
208000024827 Alzheimer disease Diseases 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
201000001320 Atherosclerosis Diseases 0.000 description 2
208000014644 Brain disease Diseases 0.000 description 2
208000032274 Encephalopathy Diseases 0.000 description 2
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical class C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 2
RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 description 2
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/72—Nitrogen atoms
- C07D213/73—Unsubstituted amino or imino radicals
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07K16/2878—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
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- A—HUMAN NECESSITIES
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- A01K2267/0325—Animal model for autoimmune diseases
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
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NO20010031A 1998-07-08 2001-01-03 Derivater av 2-aminopyridiner, anvendelse av dem som medikamenter og farmasoytiske preparater inneholdende dem NO318383B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
FR9808732A FR2780971B1 (fr)	1998-07-08	1998-07-08	Nouveaux derives de 2-aminopyridines, leur application en tant que medicaments et compositions pharmaceutiques les contenant
FR9904133A FR2791674A1 (fr)	1999-04-02	1999-04-02	Nouveaux derives de 2-aminopyridines, leur utilisation en tant que medicaments et compositions pharmaceutiques les contenant
PCT/FR1999/001610 WO2000002860A1 (fr)	1998-07-08	1999-07-05	Derives de 2-aminopyridines, leur utilisation en tant que medicaments et compositions pharmaceutiques les contenant

Publications (3)

Publication Number	Publication Date
NO20010031D0 NO20010031D0 (no)	2001-01-03
NO20010031L NO20010031L (no)	2001-01-05
NO318383B1 true NO318383B1 (no)	2005-03-14

Family

ID=26234430

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20010031A NO318383B1 (no)	1998-07-08	2001-01-03	Derivater av 2-aminopyridiner, anvendelse av dem som medikamenter og farmasoytiske preparater inneholdende dem

Country Status (19)

Country	Link
US (2)	US6762176B1 (es)
EP (1)	EP1095020B1 (es)
JP (1)	JP2002520317A (es)
AR (1)	AR019190A1 (es)
AT (1)	ATE303363T1 (es)
AU (1)	AU756221B2 (es)
CA (1)	CA2337258A1 (es)
CZ (1)	CZ299818B6 (es)
DE (1)	DE69927033T2 (es)
DK (1)	DK1095020T3 (es)
ES (1)	ES2249015T3 (es)
HU (1)	HUP0105073A3 (es)
IL (2)	IL140525A0 (es)
MY (1)	MY128840A (es)
NO (1)	NO318383B1 (es)
PL (1)	PL345354A1 (es)
RU (1)	RU2226527C2 (es)
TW (1)	TW509677B (es)
WO (1)	WO2000002860A1 (es)

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US20050239892A1 (en) *	2003-11-21	2005-10-27	Trustees Of Tufts College	Therapeutic avenathramide compounds
UA87854C2 (en) *	2004-06-07	2009-08-25	Мерк Энд Ко., Инк.	N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators
BRPI0516115A (pt) *	2004-10-14	2008-08-26	Abbott Gmbh & Co Kg	compostos arilsulfonilmetil ou arilsulfonamida aromáticos substituìdos adequados para tratar distúrbios que respondem à modulação do receptor de dopamina d3
US7511035B2 (en) *	2005-01-25	2009-03-31	Glaxo Group Limited	Antibacterial agents
CA2597616A1 (en) *	2005-02-17	2006-08-24	Wyeth	Cycloalkylfused indole, benzothiophene, benzofuran and indene derivatives
ATE552246T1 (de)	2005-05-31	2012-04-15	Pfizer	Substituierte aryloxy-n- bicyclomethylacetamidverbindungen als vr1- antagonisten
US20090318290A1 (en) *	2006-07-06	2009-12-24	Bayer Cropscience Sa	N-(4-pyridin-2-ylbutyl) benzamide derivatives and their use as fungicides
WO2008112164A2 (en)	2007-03-08	2008-09-18	The Board Of Trustees Of The Leland Stanford Junior University	Mitochondrial aldehyde dehydrogenase-2 modulators and methods of use thereof
JP2012502048A (ja) *	2008-09-08	2012-01-26	ボードオブトラスティーズオブザレランドスタンフォードジュニアユニバーシティ	アルデヒドデヒドロゲナーゼ活性のモジュレーターおよびその使用方法
KR20110082180A (ko)	2008-10-28	2011-07-18	더 보드 오브 트러스티스 오브 더 리랜드 스탠포드 쥬니어 유니버시티	알데히드 탈수소효소의 조절자 및 그것의 사용방법
WO2012149106A1 (en)	2011-04-29	2012-11-01	The Board Of Trustees Of The Leland Stanford Junior University	Compositions and methods for increasing proliferation of adult salivary stem cells
US9388156B2 (en)	2012-07-12	2016-07-12	Khondiron IP B.V.	Chromanyl derivatives for treating mitochondrial disease
LT2872497T (lt) *	2012-07-12	2017-04-25	Khondrion Ip B.V.	Chromanilo dariniai, skirti mitochondrinių ligų gydymui
NL2010010C2 (en)	2012-12-19	2014-06-23	Sulfateq B V	Compounds for protection of cells.
JP6410790B2 (ja)	2013-03-14	2018-10-24	ザボードオブトラスティーズオブザレランドスタンフォードジュニアユニバーシティー	ミトコンドリアアルデヒドデヒドロゲナーゼ−２調節因子およびその使用方法
WO2016188766A1 (en) *	2015-05-22	2016-12-01	Sulfateq B.V.	Compound for the prophylaxis or treatment of organ damage
PL3319959T3 (pl)	2015-07-06	2022-02-14	Alkermes, Inc.	Hetero-haloinhibitory deacetylazy histonowej
WO2017007755A1 (en)	2015-07-06	2017-01-12	Rodin Therapeutics, Inc.	Heterobicyclic n-aminophenyl-amides as inhibitors of histone deacetylase
EP3568135B1 (en)	2017-01-11	2021-04-07	Alkermes, Inc.	Bicyclic inhibitors of histone deacetylase
JP7152471B2 (ja)	2017-08-07	2022-10-12	ロダン・セラピューティクス，インコーポレーテッド	ヒストン脱アセチル化酵素の二環阻害剤
CN108558817B (zh) *	2018-03-30	2021-07-09	宁波大学	一种异香豆素类衍生物及其制备方法和用途

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US3037988A (en) *		1962-06-05		Benzoylamiivomethylpykidines
DE2830351A1 (de)	1978-07-11	1980-01-24	Consortium Elektrochem Ind	Acylanilide
US4180574A (en)	1978-12-26	1979-12-25	Abbott Laboratories	Certain ovicidal piperazines
US4386209A (en) *	1982-04-08	1983-05-31	Reilly Tar & Chemical Corporation	Chichibabin reaction
JPS62223173A (ja) *	1986-03-25	1987-10-01	Otsuka Pharmaceut Factory Inc	ピリジルアミノフエノ−ル誘導体及びその製造方法
IL110172A (en) *	1993-07-22	2001-10-31	Lilly Co Eli	Bicycle compounds and pharmaceuticals containing them
AU4515696A (en) *	1994-12-12	1996-07-03	Merck & Co., Inc.	Substituted 2-aminopyridines as inhibitors of nitric oxide synthase
GB9506188D0 (en)	1995-03-27	1995-05-17	Fujisawa Pharmaceutical Co	Amidine derivatives
CA2197364A1 (en) *	1996-02-15	1997-08-16	Toshikazu Suzuki	Phenol compound and process for preparing the same
DK0891332T3 (da) *	1996-03-29	2004-07-05	Pfizer	6-phenylpyridyl-2-aminderivater
HN1997000027A (es) *	1996-12-06	1997-06-05	Pfizer Prod Inc	Derivados de 6-fenil piridil - 2 amina
FR2761066B1 (fr) *	1997-03-24	2000-11-24	Sod Conseils Rech Applic	Nouveaux derives du 2-(iminomethyl)amino-phenyle, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant
FR2764889B1 (fr) *	1997-06-20	2000-09-01	Sod Conseils Rech Applic	Nouveaux derives du 2-(iminomethyl)amino-phenyle, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant

1999
- 1999-06-30 AR ARP990103182A patent/AR019190A1/es unknown
- 1999-07-01 MY MYPI99002793A patent/MY128840A/en unknown
- 1999-07-05 DE DE69927033T patent/DE69927033T2/de not_active Expired - Fee Related
- 1999-07-05 US US09/743,043 patent/US6762176B1/en not_active Expired - Fee Related
- 1999-07-05 ES ES99929395T patent/ES2249015T3/es not_active Expired - Lifetime
- 1999-07-05 IL IL14052599A patent/IL140525A0/xx active IP Right Grant
- 1999-07-05 CA CA002337258A patent/CA2337258A1/fr not_active Abandoned
- 1999-07-05 CZ CZ20010086A patent/CZ299818B6/cs not_active IP Right Cessation
- 1999-07-05 WO PCT/FR1999/001610 patent/WO2000002860A1/fr active IP Right Grant
- 1999-07-05 JP JP2000559091A patent/JP2002520317A/ja active Pending
- 1999-07-05 AU AU46223/99A patent/AU756221B2/en not_active Ceased
- 1999-07-05 DK DK99929395T patent/DK1095020T3/da active
- 1999-07-05 AT AT99929395T patent/ATE303363T1/de not_active IP Right Cessation
- 1999-07-05 EP EP99929395A patent/EP1095020B1/fr not_active Expired - Lifetime
- 1999-07-05 HU HU0105073A patent/HUP0105073A3/hu unknown
- 1999-07-05 PL PL99345354A patent/PL345354A1/xx not_active Application Discontinuation
- 1999-07-05 RU RU2001103646/04A patent/RU2226527C2/ru not_active IP Right Cessation
- 1999-08-18 TW TW088111513A patent/TW509677B/zh not_active IP Right Cessation
2000
- 2000-12-25 IL IL140525A patent/IL140525A/en not_active IP Right Cessation
2001
- 2001-01-03 NO NO20010031A patent/NO318383B1/no not_active IP Right Cessation
2003
- 2003-04-02 US US10/405,828 patent/US6727239B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
IL140525A (en)	2006-08-01
AU4622399A (en)	2000-02-01
PL345354A1 (en)	2001-12-17
DE69927033D1 (de)	2005-10-06
IL140525A0 (en)	2002-02-10
CZ200186A3 (en)	2001-05-16
TW509677B (en)	2002-11-11
JP2002520317A (ja)	2002-07-09
DE69927033T2 (de)	2006-06-14
EP1095020A1 (fr)	2001-05-02
AU756221B2 (en)	2003-01-09
DK1095020T3 (da)	2006-01-16
AR019190A1 (es)	2001-12-26
ES2249015T3 (es)	2006-03-16
MY128840A (en)	2007-02-28
WO2000002860A1 (fr)	2000-01-20
HUP0105073A3 (en)	2002-10-28
NO20010031L (no)	2001-01-05
US6727239B1 (en)	2004-04-27
ATE303363T1 (de)	2005-09-15
US6762176B1 (en)	2004-07-13
CZ299818B6 (cs)	2008-12-03
RU2226527C2 (ru)	2004-04-10
HUP0105073A2 (hu)	2002-04-29
CA2337258A1 (fr)	2000-01-20
EP1095020B1 (fr)	2005-08-31
NO20010031D0 (no)	2001-01-03

Legal Events

Date	Code	Title	Description
2010-03-01	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO318383B1 (no)	2005-03-14	Derivater av 2-aminopyridiner, anvendelse av dem som medikamenter og farmasoytiske preparater inneholdende dem
CN110041327B (zh)	2022-01-21	吡啶酮衍生物、其组合物及作为抗流感病毒药物的应用
EP1536797B1 (en)	2007-04-04	1-amido-4-phenyl-4-benzyloxymethyl-piperidine derivatives and related comounds as neurokinin-1 (nk-1) antagonsists for the treatment of emesis, depression, anxiety and cough
TWI360539B (en)	2012-03-21	3-carbamoyl-2-pyridone derivatives
JPH06107637A (ja)	1994-04-19	ベンズアニリド誘導体
CA3000483A1 (en)	2017-04-13	Compounds, compositions, and methods for modulating cftr
KR20070091634A (ko)	2007-09-11	염증 치료시 ｃｘｃｒ2 억제제로서 사용하기 위한 융합된비사이클릭 카복스아미드 유도체
EP2158201B1 (fr)	2011-04-13	Derives de 7-alkynyl-1,8-naphthyridones, leur preparation et leur application en therapeutique
EP1318149A1 (fr)	2003-06-11	Dérivés d'amidines. leur préparation et leur application à titre de médicaments et les compositions pharmaceutiques les contenant
JPH10503174A (ja)	1998-03-24	Ｐｄｅｉｖインヒビターとして有用なトリ置換フェニル誘導体
WO2003010146A1 (fr)	2003-02-06	Composes derives de quinoleine et quinoxaline, preparation et utilisations
JPH04503212A (ja)	1992-06-11	５―リポキシゲナーゼ阻止剤としての４―ヒドロキシチアゾール
HU205905B (en)	1992-07-28	Process for producing pyridine-2,4- and -2,5-dicarboxylic acid derivatives and pharmaceutical compositions containing them
KR20150022789A (ko)	2015-03-04	포스포디에스테라제 억제제로서 1-페닐-2-피리디닐 알킬 알코올의 유도체
FR2720396A1 (fr)	1995-12-01	Nouveaux N-pyridyl carboxamides et dérivés leur procédé de préparation et les compositions pharmaceutiques qui les contiennent.
NO172392B (no)	1993-04-05	Analogifremgangsmaate for fremstilling av 1h,3h-(1,2-c)-pyrrolo-7-tiazolkarboksamider
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