SK18952001A3 - Inhibítory replikácie respiračného syncyciálneho vírusu - Google Patents
Inhibítory replikácie respiračného syncyciálneho vírusu Download PDFInfo
- Publication number
- SK18952001A3 SK18952001A3 SK1895-2001A SK18952001A SK18952001A3 SK 18952001 A3 SK18952001 A3 SK 18952001A3 SK 18952001 A SK18952001 A SK 18952001A SK 18952001 A3 SK18952001 A3 SK 18952001A3
- Authority
- SK
- Slovakia
- Prior art keywords
- formula
- alkyl
- piperidinyl
- amine
- hydrogen
- Prior art date
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- 241000725643 Respiratory syncytial virus Species 0.000 title abstract description 4
- 239000003112 inhibitor Substances 0.000 title abstract 2
- 230000029812 viral genome replication Effects 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 163
- -1 homopiperidinyl Chemical group 0.000 claims abstract description 120
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 69
- 239000001257 hydrogen Substances 0.000 claims abstract description 61
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 40
- 125000001424 substituent group Chemical group 0.000 claims abstract description 34
- 238000002360 preparation method Methods 0.000 claims abstract description 30
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 21
- 125000003118 aryl group Chemical group 0.000 claims abstract description 21
- 150000001412 amines Chemical class 0.000 claims abstract description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 20
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract description 14
- 239000003814 drug Substances 0.000 claims abstract description 14
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 12
- 239000002184 metal Chemical class 0.000 claims abstract description 12
- 229910052751 metal Inorganic materials 0.000 claims abstract description 12
- 239000000651 prodrug Substances 0.000 claims abstract description 12
- 229940002612 prodrug Drugs 0.000 claims abstract description 12
- 150000001204 N-oxides Chemical class 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 4
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims abstract description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims abstract description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract 2
- 239000002904 solvent Substances 0.000 claims description 127
- 125000000217 alkyl group Chemical group 0.000 claims description 109
- 238000006243 chemical reaction Methods 0.000 claims description 77
- 239000002253 acid Substances 0.000 claims description 45
- 239000012442 inert solvent Substances 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 239000002585 base Substances 0.000 claims description 38
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 34
- 150000002431 hydrogen Chemical class 0.000 claims description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 239000003638 chemical reducing agent Substances 0.000 claims description 21
- 238000000034 method Methods 0.000 claims description 21
- 125000006239 protecting group Chemical group 0.000 claims description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 18
- 238000010511 deprotection reaction Methods 0.000 claims description 18
- 230000000840 anti-viral effect Effects 0.000 claims description 16
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 13
- 150000001721 carbon Chemical group 0.000 claims description 12
- 238000005576 amination reaction Methods 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 8
- 101150065749 Churc1 gene Proteins 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 230000009385 viral infection Effects 0.000 claims description 7
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 6
- 208000036142 Viral infection Diseases 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 5
- 125000004414 alkyl thio group Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 5
- 230000003000 nontoxic effect Effects 0.000 claims description 5
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 4
- 102100038239 Protein Churchill Human genes 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 229910052698 phosphorus Inorganic materials 0.000 claims description 4
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 4
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 3
- 125000004104 aryloxy group Chemical group 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 150000004696 coordination complex Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 239000012458 free base Substances 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000004590 pyridopyridyl group Chemical group N1=C(C=CC2=C1C=CC=N2)* 0.000 claims description 3
- DQBYJNVVCVXGIK-UHFFFAOYSA-N 1-(quinolin-8-ylmethyl)benzimidazol-2-amine Chemical compound C1=CN=C2C(CN3C4=CC=CC=C4N=C3N)=CC=CC2=C1 DQBYJNVVCVXGIK-UHFFFAOYSA-N 0.000 claims description 2
- JWYUFVNJZUSCSM-UHFFFAOYSA-N 2-aminobenzimidazole Chemical compound C1=CC=C2NC(N)=NC2=C1 JWYUFVNJZUSCSM-UHFFFAOYSA-N 0.000 claims description 2
- JYYASXKOESRUKU-UHFFFAOYSA-N 4-methyl-1h-benzimidazol-2-amine Chemical compound CC1=CC=CC2=C1NC(N)=N2 JYYASXKOESRUKU-UHFFFAOYSA-N 0.000 claims description 2
- QUDVZCYXKXSGTN-UHFFFAOYSA-N O.Cl.Cl.Cl.C(CCN)N Chemical compound O.Cl.Cl.Cl.C(CCN)N QUDVZCYXKXSGTN-UHFFFAOYSA-N 0.000 claims description 2
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- YQDRPPGDAHONPA-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-1-(isoquinolin-1-ylmethyl)benzimidazol-2-amine;trihydrate;trihydrochloride Chemical compound O.O.O.Cl.Cl.Cl.C1CN(CC(N)C(C)C)CCC1NC1=NC2=CC=CC=C2N1CC1=NC=CC2=CC=CC=C12 YQDRPPGDAHONPA-UHFFFAOYSA-N 0.000 claims description 2
- OVVMSCLHGVMCQJ-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-3-(quinolin-2-ylmethyl)imidazo[4,5-b]pyridin-2-amine Chemical compound C1CN(CC(N)C(C)C)CCC1NC1=NC2=CC=CN=C2N1CC1=CC=C(C=CC=C2)C2=N1 OVVMSCLHGVMCQJ-UHFFFAOYSA-N 0.000 claims description 2
- MCRRDAYTPSNFAY-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-3-(quinolin-8-ylmethyl)imidazo[4,5-c]pyridin-2-amine;tetrahydrate;trihydrochloride Chemical compound O.O.O.O.Cl.Cl.Cl.C1CN(CC(N)C(C)C)CCC1NC1=NC2=CC=NC=C2N1CC1=CC=CC2=CC=CN=C12 MCRRDAYTPSNFAY-UHFFFAOYSA-N 0.000 claims description 2
- LIMZOOFCNNTFNO-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-7-methyl-3-(quinolin-8-ylmethyl)imidazo[4,5-b]pyridin-2-amine;hydrate;tetrahydrochloride Chemical compound O.Cl.Cl.Cl.Cl.C1CN(CC(N)C(C)C)CCC1NC1=NC2=C(C)C=CN=C2N1CC1=CC=CC2=CC=CN=C12 LIMZOOFCNNTFNO-UHFFFAOYSA-N 0.000 claims description 2
- PKKIEWLTEGUWQX-UHFFFAOYSA-N n-[1-(2-aminoethyl)piperidin-4-yl]-1-[2-ethoxyethoxy(quinolin-8-yl)methyl]-4-methylbenzimidazol-2-amine;hydrate Chemical compound O.C=1C=CC2=CC=CN=C2C=1C(OCCOCC)N(C1=CC=CC(C)=C1N=1)C=1NC1CCN(CCN)CC1 PKKIEWLTEGUWQX-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 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 2
- 230000009466 transformation Effects 0.000 claims description 2
- 125000001475 halogen functional group Chemical group 0.000 claims 3
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical compound [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 claims 2
- 239000005749 Copper compound Substances 0.000 claims 1
- GAGDHGJTAUUUHC-UHFFFAOYSA-N N-[1-(2-aminoethyl)piperidin-4-yl]-1-(2-chloro-5,6,7,8-tetrahydroquinoxalin-5-yl)-4-methylbenzimidazol-2-amine trihydrate trihydrochloride Chemical compound O.O.O.Cl.Cl.Cl.N=1C=2C(C)=CC=CC=2N(C2C3=NC=C(Cl)N=C3CCC2)C=1NC1CCN(CCN)CC1 GAGDHGJTAUUUHC-UHFFFAOYSA-N 0.000 claims 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims 1
- 150000001880 copper compounds Chemical class 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- NOPNILZZVYTFAO-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-1-(quinolin-8-ylmethyl)imidazo[4,5-b]pyridin-2-amine;dihydrate;trihydrochloride Chemical compound O.O.Cl.Cl.Cl.C1CN(CC(N)C(C)C)CCC1NC1=NC2=NC=CC=C2N1CC1=CC=CC2=CC=CN=C12 NOPNILZZVYTFAO-UHFFFAOYSA-N 0.000 claims 1
- YYHBFBPDJAVWDH-UHFFFAOYSA-N n-[1-(2-amino-3-methylbutyl)piperidin-4-yl]-4-methyl-1-(5,6,7,8-tetrahydroquinoxalin-5-yl)benzimidazol-2-amine Chemical compound C1CN(CC(N)C(C)C)CCC1NC1=NC2=C(C)C=CC=C2N1C1C2=NC=CN=C2CCC1 YYHBFBPDJAVWDH-UHFFFAOYSA-N 0.000 claims 1
- MWRDNDIBVPSSJM-UHFFFAOYSA-N n-[1-(2-aminoethyl)piperidin-4-yl]-7-methyl-3-(quinolin-8-ylmethyl)imidazo[4,5-b]pyridin-2-amine;trihydrate;tetrahydrochloride Chemical compound O.O.O.Cl.Cl.Cl.Cl.N=1C=2C(C)=CC=NC=2N(CC=2C3=NC=CC=C3C=CC=2)C=1NC1CCN(CCN)CC1 MWRDNDIBVPSSJM-UHFFFAOYSA-N 0.000 claims 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims 1
- 238000000844 transformation Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 138
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 3
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 abstract 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 125000003373 pyrazinyl group Chemical group 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 254
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 95
- 239000000460 chlorine Substances 0.000 description 82
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 73
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 57
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 55
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 52
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000012044 organic layer Substances 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
- 239000000243 solution Substances 0.000 description 35
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000003480 eluent Substances 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 239000003054 catalyst Substances 0.000 description 31
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
- 238000010992 reflux Methods 0.000 description 27
- 150000003254 radicals Chemical class 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 25
- 239000002244 precipitate Substances 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 238000004440 column chromatography Methods 0.000 description 24
- 125000005843 halogen group Chemical group 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000006722 reduction reaction Methods 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- 239000000047 product Substances 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 14
- 239000010410 layer Substances 0.000 description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 description 14
- 235000011181 potassium carbonates Nutrition 0.000 description 14
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
- 229910052763 palladium Inorganic materials 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 8
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 8
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- 150000001298 alcohols Chemical class 0.000 description 8
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
- 229910052801 chlorine Inorganic materials 0.000 description 8
- 229930195734 saturated hydrocarbon Natural products 0.000 description 8
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 7
- 206010061603 Respiratory syncytial virus infection Diseases 0.000 description 7
- 241000700605 Viruses Species 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 108010037444 diisopropylglutathione ester Proteins 0.000 description 7
- 229910052700 potassium Inorganic materials 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
- 125000002619 bicyclic group Chemical group 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 description 6
- 229910052697 platinum Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 229910052794 bromium Inorganic materials 0.000 description 5
- 239000002552 dosage form Substances 0.000 description 5
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- QSJXEFYPDANLFS-UHFFFAOYSA-N Diacetyl Chemical compound CC(=O)C(C)=O QSJXEFYPDANLFS-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- 239000007868 Raney catalyst Substances 0.000 description 4
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 4
- 229910000564 Raney nickel Inorganic materials 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
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- OUMXQSOAWCCKHV-UHFFFAOYSA-N n-[1-(2-aminoethyl)piperidin-4-yl]-1-(quinolin-2-ylmethyl)benzimidazol-2-amine;hydrate;tetrahydrochloride Chemical compound O.Cl.Cl.Cl.Cl.C1CN(CCN)CCC1NC1=NC2=CC=CC=C2N1CC1=CC=C(C=CC=C2)C2=N1 OUMXQSOAWCCKHV-UHFFFAOYSA-N 0.000 description 1
- UODUKZSHCSAPBU-UHFFFAOYSA-N n-[1-(2-aminoethyl)piperidin-4-yl]-1-(quinolin-4-ylmethyl)benzimidazol-2-amine Chemical compound C1CN(CCN)CCC1NC1=NC2=CC=CC=C2N1CC1=CC=NC2=CC=CC=C12 UODUKZSHCSAPBU-UHFFFAOYSA-N 0.000 description 1
- WQIFDTRADYWZNQ-UHFFFAOYSA-N n-[1-(2-aminoethyl)piperidin-4-yl]-3-(quinolin-2-ylmethyl)imidazo[4,5-b]pyridin-2-amine;trihydrate;trihydrochloride Chemical compound O.O.O.Cl.Cl.Cl.C1CN(CCN)CCC1NC1=NC2=CC=CN=C2N1CC1=CC=C(C=CC=C2)C2=N1 WQIFDTRADYWZNQ-UHFFFAOYSA-N 0.000 description 1
- GZFUQWXUSLNEIN-UHFFFAOYSA-N n-[1-(2-aminoethyl)piperidin-4-yl]-4-methyl-1-(1-quinolin-8-ylethyl)benzimidazol-2-amine;hydrate Chemical compound O.C=1C=CC2=CC=CN=C2C=1C(C)N(C1=CC=CC(C)=C1N=1)C=1NC1CCN(CCN)CC1 GZFUQWXUSLNEIN-UHFFFAOYSA-N 0.000 description 1
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- YTYUPAYEZWIDOX-UHFFFAOYSA-N n-piperidin-4-yl-1-(quinolin-2-ylmethyl)benzimidazol-2-amine;dihydrochloride Chemical compound Cl.Cl.C=1C=C2C=CC=CC2=NC=1CN(C1=CC=CC=C1N=1)C=1NC1CCNCC1 YTYUPAYEZWIDOX-UHFFFAOYSA-N 0.000 description 1
- HLDKASZRJPWADR-UHFFFAOYSA-N n-piperidin-4-yl-1h-benzimidazol-2-amine;dihydrobromide Chemical compound Br.Br.C1CNCCC1NC1=NC2=CC=CC=C2N1 HLDKASZRJPWADR-UHFFFAOYSA-N 0.000 description 1
- ZGBBDLGXELWVIC-UHFFFAOYSA-N n-piperidin-4-yl-3-(quinolin-8-ylmethyl)imidazo[4,5-b]pyridin-2-amine Chemical compound C=1C=CC2=CC=CN=C2C=1CN(C1=NC=CC=C1N=1)C=1NC1CCNCC1 ZGBBDLGXELWVIC-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- UQQALTRHPDPRQC-UHFFFAOYSA-N nitrogen tribromide Chemical compound BrN(Br)Br UQQALTRHPDPRQC-UHFFFAOYSA-N 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940127073 nucleoside analogue Drugs 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 150000001451 organic peroxides Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 229960000402 palivizumab Drugs 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000003961 penetration enhancing agent Substances 0.000 description 1
- FDPIMTJIUBPUKL-UHFFFAOYSA-N pentan-3-one Chemical compound CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 238000000053 physical method Methods 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 150000003053 piperidines Chemical class 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- CGYHPRUOANQIRZ-UHFFFAOYSA-N pyridin-2-amine dihydrate trihydrochloride Chemical compound C1=CC=NC(=C1)N.O.O.Cl.Cl.Cl CGYHPRUOANQIRZ-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- RZIPENSSTUBRAA-UHFFFAOYSA-N quinolin-6-ylmethanamine Chemical compound N1=CC=CC2=CC(CN)=CC=C21 RZIPENSSTUBRAA-UHFFFAOYSA-N 0.000 description 1
- WPYJKGWLDJECQD-UHFFFAOYSA-N quinoline-2-carbaldehyde Chemical compound C1=CC=CC2=NC(C=O)=CC=C21 WPYJKGWLDJECQD-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000010956 selective crystallization Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- PFUVRDFDKPNGAV-UHFFFAOYSA-N sodium peroxide Chemical compound [Na+].[Na+].[O-][O-] PFUVRDFDKPNGAV-UHFFFAOYSA-N 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 125000003375 sulfoxide group Chemical group 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- OSDUDPQWLGJWGL-UHFFFAOYSA-N tert-butyl 4-(1h-benzimidazol-2-ylamino)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=NC2=CC=CC=C2N1 OSDUDPQWLGJWGL-UHFFFAOYSA-N 0.000 description 1
- GHKMYZWJMNJVBX-UHFFFAOYSA-N tert-butyl 4-[[1-(quinolin-2-ylmethyl)benzimidazol-2-yl]amino]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1NC1=NC2=CC=CC=C2N1CC1=CC=C(C=CC=C2)C2=N1 GHKMYZWJMNJVBX-UHFFFAOYSA-N 0.000 description 1
- MKCXQUIBDSPYFO-UHFFFAOYSA-N tert-butyl-(1-hydroxy-3-methylbutan-2-yl)carbamic acid Chemical compound CC(C)C(CO)N(C(O)=O)C(C)(C)C MKCXQUIBDSPYFO-UHFFFAOYSA-N 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- CVQPQLRQAKXFFF-UHFFFAOYSA-N trihydrate;trihydrochloride Chemical compound O.O.O.Cl.Cl.Cl CVQPQLRQAKXFFF-UHFFFAOYSA-N 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP99202089 | 1999-06-28 | ||
| PCT/EP2000/005677 WO2001000615A1 (en) | 1999-06-28 | 2000-06-20 | Respiratory syncytial virus replication inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SK18952001A3 true SK18952001A3 (sk) | 2002-11-06 |
Family
ID=8240374
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1895-2001A SK18952001A3 (sk) | 1999-06-28 | 2000-06-20 | Inhibítory replikácie respiračného syncyciálneho vírusu |
Country Status (34)
| Country | Link |
|---|---|
| US (2) | US7071192B1 (cs) |
| EP (2) | EP1400519B1 (cs) |
| JP (1) | JP2003503403A (cs) |
| KR (1) | KR100731273B1 (cs) |
| CN (1) | CN1171887C (cs) |
| AR (1) | AR024495A1 (cs) |
| AT (2) | ATE259796T1 (cs) |
| AU (1) | AU774829B2 (cs) |
| BG (1) | BG65373B1 (cs) |
| BR (1) | BR0011997A (cs) |
| CA (1) | CA2376785A1 (cs) |
| CZ (1) | CZ20014573A3 (cs) |
| DE (2) | DE60008382T2 (cs) |
| DK (1) | DK1196410T3 (cs) |
| EA (1) | EA004746B1 (cs) |
| EE (1) | EE04592B1 (cs) |
| ES (2) | ES2215670T3 (cs) |
| HK (1) | HK1045998B (cs) |
| HR (2) | HRP20010934A2 (cs) |
| HU (1) | HUP0201789A3 (cs) |
| IL (2) | IL147328A0 (cs) |
| MX (1) | MXPA02000117A (cs) |
| MY (1) | MY129810A (cs) |
| NO (1) | NO321599B1 (cs) |
| NZ (1) | NZ515392A (cs) |
| PL (1) | PL200694B1 (cs) |
| PT (1) | PT1196410E (cs) |
| SI (1) | SI1196410T1 (cs) |
| SK (1) | SK18952001A3 (cs) |
| TR (2) | TR200500707T2 (cs) |
| TW (1) | TWI267513B (cs) |
| UA (1) | UA75866C2 (cs) |
| WO (1) | WO2001000615A1 (cs) |
| ZA (1) | ZA200110473B (cs) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6495580B1 (en) | 1998-01-29 | 2002-12-17 | Viropharma Incorporated | Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases |
| CA2336909C (en) | 1998-07-15 | 2009-10-20 | Teijin Limited | Thiobenzimidazole derivatives which are useful as inhibitors of human chymase activity |
| US20040010004A1 (en) | 2000-01-17 | 2004-01-15 | Naoki Tsuchiya | Benzimidazole derivatives |
| PT1249450E (pt) * | 2000-01-17 | 2008-01-02 | Teijin Pharma Ltd | Derivados de benzimidazole como inibidores de quimase humana |
| US6489338B2 (en) | 2000-06-13 | 2002-12-03 | Bristol-Myers Squibb Company | Imidazopyridine and imidazopyrimidine antiviral agents |
| US6506738B1 (en) | 2000-09-27 | 2003-01-14 | Bristol-Myers Squibb Company | Benzimidazolone antiviral agents |
| WO2002048147A2 (en) | 2000-12-15 | 2002-06-20 | Glaxo Group Limited | Pyrazolopyridines |
| WO2002048148A2 (en) | 2000-12-15 | 2002-06-20 | Glaxo Group Limited | Pyrazolopyridine derivatives |
| US6774134B2 (en) | 2000-12-20 | 2004-08-10 | Bristol-Myers Squibb Company | Heterocyclic substituted 2-methyl-benzimidazole antiviral agents |
| AU2002248531A1 (en) | 2001-03-08 | 2002-09-24 | Smithkline Beecham Corporation | Pyrazolopyriadine derivatives |
| JP4237497B2 (ja) | 2001-03-30 | 2009-03-11 | スミスクライン ビーチャム コーポレーション | ピラゾロピリジン類、その調製方法及びその治療用化合物としての使用 |
| WO2002083672A1 (en) | 2001-04-10 | 2002-10-24 | Smithkline Beecham Corporation | Antiviral pyrazolopyridine compounds |
| DE60204452T2 (de) | 2001-04-27 | 2005-12-15 | Smithkline Beecham Corp. | Pyrazolo[1,5a]Pyridinderivate |
| US7030150B2 (en) | 2001-05-11 | 2006-04-18 | Trimeris, Inc. | Benzimidazole compounds and antiviral uses thereof |
| DE60214179T2 (de) | 2001-06-21 | 2007-01-04 | Smithkline Beecham Corp. | Imidazo-1,2-A/Pyriden-Derivate zur Prophylaxe und Behandlung von Herpes-Infektionen |
| US7244740B2 (en) | 2001-10-05 | 2007-07-17 | Smithkline Beecham Corporation | Imidazo-pyridine derivatives for use in the treatment of herpes viral infection |
| US6919331B2 (en) | 2001-12-10 | 2005-07-19 | Bristol-Myers Squibb Company | Substituted 2-methyl-benzimidazole respiratory syncytial virus antiviral agents |
| EP1453830B1 (en) | 2001-12-11 | 2007-09-12 | SmithKline Beecham Corporation | Pyrazolo-pyridine derivatives as antiherpes agents |
| US7244847B2 (en) * | 2002-02-06 | 2007-07-17 | Isis Pharmaceuticals, Inc. | Benzimidazole compounds |
| CA2495245A1 (en) | 2002-08-09 | 2004-02-19 | Viropharma Incorporated | Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases |
| US8202896B2 (en) | 2002-08-09 | 2012-06-19 | Microdose Therapeutx, Inc. | Compounds, compositions and methods for treating or preventing pneumovirus infection and associated diseases |
| JP2006504728A (ja) | 2002-10-03 | 2006-02-09 | スミスクライン ビーチャム コーポレーション | ピラソロピリジン誘導体系治療用化合物 |
| EP1682547B1 (en) * | 2003-10-30 | 2012-10-24 | Boehringer Ingelheim (Canada) Ltd. | Rsv polymerase inhibitors |
| DK1697347T3 (da) * | 2003-12-18 | 2011-06-06 | Tibotec Pharm Ltd | 5- eller 6-substituerede benzimidazolderivater som inhibitorer af replikation af respiratorisk syncytial-virus |
| MXPA06007110A (es) * | 2003-12-18 | 2006-08-23 | Tibotec Pharm Ltd | Derivados de los amino-bencimidazoles como inhibidores de la replicacion del virus sincitial respiratorio. |
| AR046972A1 (es) * | 2003-12-18 | 2006-01-04 | Tibotec Pharm Ltd | Derivados de los amino-bencimidazoles como inhibidores de la replicacion del virus sincitial respiratorio |
| AR046971A1 (es) * | 2003-12-18 | 2006-01-04 | Tibotec Pharm Ltd | Aminobenzoimidazoles y benzoimidazoles como inhibidores de la replicacion del virus sincitial respiratorio |
| AR046959A1 (es) * | 2003-12-18 | 2006-01-04 | Tibotec Pharm Ltd | Morfolinilo que contiene bencimidazoles como inhibidores de la replicacion del virus sincitial respiratorio |
| CN1894239A (zh) | 2003-12-18 | 2007-01-10 | 泰博特克药品有限公司 | 作为呼吸道合胞病毒复制的抑制剂的哌啶－氨基－苯并咪唑类衍生物 |
| MX2007011292A (es) | 2005-03-17 | 2007-11-07 | Tibotec Pharm Ltd | 1,3-dihidro-bencimidazol-2-ilidenaminas como inhibidores de replicacion de virus respiratorios sinciciales. |
| CA2612264C (en) | 2005-06-20 | 2014-09-23 | Tibotec Pharmaceuticals Ltd. | Heterocyclylaminoalkyl substituted benzimidazoles |
| BRPI0612628B8 (pt) | 2005-06-20 | 2021-05-25 | Janssen R & D Ireland | 1-(2-amina-3-(alquil substituído)-3h-benzimidazolil)metil]-3-substituído-1,3-diidro-benzoimidazol-2-onas com atividade sobre vírus sincicial respiratório, seu processo de preparação e composição farmacêutica que os compreende |
| CL2008001003A1 (es) | 2007-04-11 | 2008-10-17 | Actelion Pharmaceuticals Ltd | Compuestos derivados de oxazolidinona; composicion farmaceutica que comprende a dichos compuestos; y su uso para preparar un medicamento para tratar una infeccion bacteriana. |
| WO2010045276A2 (en) * | 2008-10-16 | 2010-04-22 | Cara Therapeutics, Inc. | Azabenzimidazolones |
| JP5487692B2 (ja) | 2009-04-10 | 2014-05-07 | 国立大学法人京都大学 | 複素環骨格を有する化合物および該化合物を不斉触媒として用いる光学活性化合物の製造方法 |
| US8993604B2 (en) | 2009-06-30 | 2015-03-31 | Siga Technologies, Inc. | Treatment and prevention of dengue virus infections |
| BRPI1009034A2 (pt) * | 2009-06-30 | 2019-09-24 | Siga Tech Inc | composição farmacêutica e método para o tratamento ou profilaxia de uma infecção viral ou doença associada a mesma |
| WO2013011932A1 (ja) | 2011-07-15 | 2013-01-24 | 塩野義製薬株式会社 | Ａｍｐｋ活性化作用を有するアザベンズイミダゾール誘導体 |
| JP6243908B2 (ja) * | 2012-08-23 | 2017-12-06 | アリオス バイオファーマ インク． | パラミクソウイルス感染症を治療するための化合物 |
| JP2016079168A (ja) | 2014-10-17 | 2016-05-16 | 塩野義製薬株式会社 | ９員縮合環誘導体 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1140119A (en) * | 1978-04-03 | 1983-01-25 | Joseph Torremans | N-heterocyclyl-4-piperidinamines |
| US4556660A (en) | 1982-07-12 | 1985-12-03 | Janssen Pharmaceutica N.V. | N-(Bicyclic heterocyclyl)-4-piperidinamines |
| US4634704A (en) | 1983-10-06 | 1987-01-06 | Janssen Pharmaceutica, N.V. | Anti-allergic five membered heterocyclic ring containing N-(bicyclic heterocycyl)-4-piperidinamines |
| US4695569A (en) | 1983-11-30 | 1987-09-22 | Janssen Pharmaceutica N.V. | Bicyclic heterocyclyl containing N-(bicyclic heterocyclyl)-4-piperidinamines |
| EP0144101B1 (en) | 1983-11-30 | 1991-02-06 | Janssen Pharmaceutica N.V. | Bicyclic heterocyclyl containing n-(bicyclic heterocyclyl)-4-piperidinamines |
| US4588722A (en) | 1984-01-09 | 1986-05-13 | Janssen Pharmaceutica N.V. | N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives |
| PH23995A (en) | 1984-01-09 | 1990-02-09 | Janssen Pharmaceutica Nv | 4((bicycle heterocyclyl)-methyl and hetero)piperidines |
| DE3781173T2 (de) | 1986-02-03 | 1992-12-17 | Janssen Pharmaceutica Nv | N-heterozyklische-4-piperidinamine enthaltende anti-histaminische zusammensetzungen. |
| US4897401A (en) | 1987-06-19 | 1990-01-30 | Janssen Pharmaceutical N.V. | N-(4-piperidinyl) bicyclic condensed 2-imidazolamine derivatives useful in treating allergic diseases |
| CA1317939C (en) * | 1987-07-01 | 1993-05-18 | Janssen Pharmaceutica Naamloze Vennootschap | ¬(bicyclic heterocyclyl)methyl and -hetero| substituted hexahydro-1h-azepines and pyrrolidines |
| GB8716313D0 (en) * | 1987-07-10 | 1987-08-19 | Janssen Pharmaceutica Nv | 2-(heterocyclylalkyl)imidazopyridines |
| US5597824A (en) | 1987-11-03 | 1997-01-28 | Abbott Laboratories | Analogs of oxetanyl purines and pyrimidines |
| IE904378A1 (en) | 1989-12-20 | 1991-07-03 | Abbott Lab | Analogs of oxetanyl purines and pyrimidines |
| KR100190299B1 (ko) | 1990-07-19 | 1999-06-01 | 디르크 반테 | 신규한 옥사졸릴 유도체 |
| NZ238863A (en) * | 1990-07-19 | 1993-03-26 | Janssen Pharmaceutica Nv | Substituted thiazolyl and pyridinyl derivatives |
| US5567824A (en) | 1994-05-24 | 1996-10-22 | Merck & Co., Inc. | Palladium catalyzed ring closure of triazolyltryptamine |
| US5693661A (en) * | 1995-06-07 | 1997-12-02 | Eli Lilly And Company | Anti-viral compounds |
| PE107598A1 (es) | 1996-09-11 | 1999-01-29 | Ucb Sa | Cetirizina util para el tratamiento de enfermedades de tipo virico |
| WO1998031363A1 (en) | 1997-01-22 | 1998-07-23 | Eli Lilly And Company | Anti-viral compounds |
| CA2293508A1 (en) | 1997-06-04 | 1998-12-10 | Louis Nickolaus Jungheim | Anti-viral compounds |
| JP2002505277A (ja) * | 1998-03-06 | 2002-02-19 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | グリシン輸送阻害剤 |
| EP1098644A1 (en) * | 1998-07-20 | 2001-05-16 | Bristol-Myers Squibb Company | Substituted benzimidazole antiviral agents |
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