TW200813070A - Antiviral agents - Google Patents

Info

Publication number

TW200813070A

TW200813070A TW096125693A TW96125693A TW200813070A TW 200813070 A TW200813070 A TW 200813070A TW 096125693 A TW096125693 A TW 096125693A TW 96125693 A TW96125693 A TW 96125693A TW 200813070 A TW200813070 A TW 200813070A

Authority

TW

Taiwan

Prior art keywords

substituted

group

methyl

compound

amino

Prior art date

2006-07-14

Links

• Espacenet
• Global Dossier
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• 239000003443 antiviral agent Substances 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 235
• 230000009385 viral infection Effects 0.000 claims abstract description 6
• -1 dilute Chemical group 0.000 claims description 343
• 125000000623 heterocyclic group Chemical group 0.000 claims description 154
• 125000001072 heteroaryl group Chemical group 0.000 claims description 113
• 125000000217 alkyl group Chemical group 0.000 claims description 87
• 125000003118 aryl group Chemical group 0.000 claims description 71
• 229910052739 hydrogen Inorganic materials 0.000 claims description 61
• 239000001257 hydrogen Substances 0.000 claims description 61
• 229910052757 nitrogen Inorganic materials 0.000 claims description 61
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 58
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 53
• 125000003107 substituted aryl group Chemical group 0.000 claims description 52
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 50
• 150000001412 amines Chemical class 0.000 claims description 45
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
• 241000711549 Hepacivirus C Species 0.000 claims description 40
• 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 37
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 37
• 150000002431 hydrogen Chemical group 0.000 claims description 35
• 125000001424 substituent group Chemical group 0.000 claims description 35
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 32
• 125000003277 amino group Chemical group 0.000 claims description 30
• 125000005842 heteroatom Chemical group 0.000 claims description 30
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
• 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 28
• 125000003545 alkoxy group Chemical group 0.000 claims description 27
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 27
• 229930192474 thiophene Natural products 0.000 claims description 26
• 239000003814 drug Substances 0.000 claims description 23
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 21
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 20
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 20
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 19
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 19
• AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 claims description 18
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims description 18
• 230000000694 effects Effects 0.000 claims description 18
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
• 125000000304 alkynyl group Chemical group 0.000 claims description 17
• 125000003342 alkenyl group Chemical group 0.000 claims description 16
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 16
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 16
• 239000007789 gas Substances 0.000 claims description 15
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 15
• 241000700605 Viruses Species 0.000 claims description 13
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 13
• 239000003795 chemical substances by application Substances 0.000 claims description 13
• 229910052717 sulfur Inorganic materials 0.000 claims description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
• 125000004429 atom Chemical group 0.000 claims description 11
• ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical class C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 11
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 11
• 239000008194 pharmaceutical composition Substances 0.000 claims description 11
• 150000003839 salts Chemical class 0.000 claims description 11
• 230000003612 virological effect Effects 0.000 claims description 11
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 9
• KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 9
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Natural products C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 9
• 238000002360 preparation method Methods 0.000 claims description 9
• 229910052707 ruthenium Inorganic materials 0.000 claims description 9
• 125000002704 decyl group Chemical group [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])C([H])([H])C([H])([H])* 0.000 claims description 8
• 241000124008 Mammalia Species 0.000 claims description 7
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
• 229940079593 drug Drugs 0.000 claims description 7
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
• 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 7
• 239000000126 substance Substances 0.000 claims description 7
• 150000003536 tetrazoles Chemical class 0.000 claims description 7
• 108060004795 Methyltransferase Proteins 0.000 claims description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 6
• 239000004305 biphenyl Substances 0.000 claims description 6
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims description 6
• 150000002923 oximes Chemical class 0.000 claims description 6
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
• 150000003254 radicals Chemical class 0.000 claims description 6
• 125000006413 ring segment Chemical group 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 0.000 claims description 6
• 208000036142 Viral infection Diseases 0.000 claims description 5
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
• 235000010290 biphenyl Nutrition 0.000 claims description 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
• ZRALSGWEFCBTJO-UHFFFAOYSA-N guanidine group Chemical group NC(=N)N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 5
• 229910052747 lanthanoid Inorganic materials 0.000 claims description 5
• 150000002602 lanthanoids Chemical class 0.000 claims description 5
• 230000001404 mediated effect Effects 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 4
• 208000005176 Hepatitis C Diseases 0.000 claims description 4
• OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 4
• 108091005804 Peptidases Proteins 0.000 claims description 4
• 239000004365 Protease Substances 0.000 claims description 4
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 4
• 150000001345 alkine derivatives Chemical group 0.000 claims description 4
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 230000003647 oxidation Effects 0.000 claims description 4
• 238000007254 oxidation reaction Methods 0.000 claims description 4
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 125000003386 piperidinyl group Chemical group 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
• 125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 4
• OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 4
• RHDYQUZYHZWTCI-UHFFFAOYSA-N 1-methoxy-4-phenylbenzene Chemical group C1=CC(OC)=CC=C1C1=CC=CC=C1 RHDYQUZYHZWTCI-UHFFFAOYSA-N 0.000 claims description 3
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 claims description 3
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
• 125000005518 carboxamido group Chemical group 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 150000002148 esters Chemical class 0.000 claims description 3
• 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 3
• 125000002541 furyl group Chemical group 0.000 claims description 3
• 125000001188 haloalkyl group Chemical group 0.000 claims description 3
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 3
• 125000002883 imidazolyl group Chemical group 0.000 claims description 3
• 239000003112 inhibitor Substances 0.000 claims description 3
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 3
• XRYGCVVVDCEPRL-UHFFFAOYSA-N n,1-dimethylpiperidin-4-amine Chemical compound CNC1CCN(C)CC1 XRYGCVVVDCEPRL-UHFFFAOYSA-N 0.000 claims description 3
• 229910052762 osmium Inorganic materials 0.000 claims description 3
• SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 claims description 3
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
• 229910021653 sulphate ion Inorganic materials 0.000 claims description 3
• 125000000335 thiazolyl group Chemical group 0.000 claims description 3
• 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 2
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
• 101710088194 Dehydrogenase Proteins 0.000 claims description 2
• 150000001204 N-oxides Chemical class 0.000 claims description 2
• 101800001019 Non-structural protein 4B Proteins 0.000 claims description 2
• 101800001014 Non-structural protein 5A Proteins 0.000 claims description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
• 125000001769 aryl amino group Chemical group 0.000 claims description 2
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
• 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
• 239000003937 drug carrier Substances 0.000 claims description 2
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
• ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
• 125000005825 oxyethoxy group Chemical group [H]C([H])(O[*:1])C([H])([H])O[*:2] 0.000 claims description 2
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 2
• 230000036961 partial effect Effects 0.000 claims description 2
• 239000007921 spray Substances 0.000 claims description 2
• 239000000758 substrate Substances 0.000 claims description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 4
• 150000003573 thiols Chemical class 0.000 claims 4
• JHZGLORTHSTEIV-UHFFFAOYSA-N CCCCCCCCCCNN=C(N)N Chemical compound CCCCCCCCCCNN=C(N)N JHZGLORTHSTEIV-UHFFFAOYSA-N 0.000 claims 3
• 125000003363 1,3,5-triazinyl group Chemical group N1=C(N=CN=C1)* 0.000 claims 2
• NLWCWEGVNJVLAX-UHFFFAOYSA-N 1-methoxy-2-phenylbenzene Chemical group COC1=CC=CC=C1C1=CC=CC=C1 NLWCWEGVNJVLAX-UHFFFAOYSA-N 0.000 claims 2
• BLRHMMGNCXNXJL-UHFFFAOYSA-N 1-methylindole Chemical compound C1=CC=C2N(C)C=CC2=C1 BLRHMMGNCXNXJL-UHFFFAOYSA-N 0.000 claims 2
• ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical class C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 claims 2
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 2
• 125000001715 oxadiazolyl group Chemical group 0.000 claims 2
• 125000003226 pyrazolyl group Chemical group 0.000 claims 2
• 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims 1
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims 1
• OTIPNGRKNOTZGJ-UHFFFAOYSA-N 1-methylperoxy-4-phenylbenzene Chemical group C1=CC(OOC)=CC=C1C1=CC=CC=C1 OTIPNGRKNOTZGJ-UHFFFAOYSA-N 0.000 claims 1
• OBSLLHNATPQFMJ-UHFFFAOYSA-N 2,4-Dimethylthiazole Chemical compound CC1=CSC(C)=N1 OBSLLHNATPQFMJ-UHFFFAOYSA-N 0.000 claims 1
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 claims 1
• XOHQKRFDBXZSNF-UHFFFAOYSA-N 3-(decylamino)propanenitrile Chemical compound CCCCCCCCCCNCCC#N XOHQKRFDBXZSNF-UHFFFAOYSA-N 0.000 claims 1
• LBSXSAXOLABXMF-UHFFFAOYSA-N 4-Vinylaniline Chemical compound NC1=CC=C(C=C)C=C1 LBSXSAXOLABXMF-UHFFFAOYSA-N 0.000 claims 1
• PMMYEEVYMWASQN-UHFFFAOYSA-N 4-hydroxyproline Chemical compound OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims 1
• RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 claims 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical group [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-N Gluconic acid Natural products OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 claims 1
• UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 claims 1
• 229930010555 Inosine Natural products 0.000 claims 1
• 244000028419 Styrax benzoin Species 0.000 claims 1
• 235000000126 Styrax benzoin Nutrition 0.000 claims 1
• 235000008411 Sumatra benzointree Nutrition 0.000 claims 1
• 125000002947 alkylene group Chemical group 0.000 claims 1
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 1
• 229960002130 benzoin Drugs 0.000 claims 1
• 125000006267 biphenyl group Chemical group 0.000 claims 1
• 238000001354 calcination Methods 0.000 claims 1
• 150000003857 carboxamides Chemical class 0.000 claims 1
• 150000001924 cycloalkanes Chemical class 0.000 claims 1
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims 1
• 229910052805 deuterium Inorganic materials 0.000 claims 1
• 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 1
• WHRIKZCFRVTHJH-UHFFFAOYSA-N ethylhydrazine Chemical compound CCNN WHRIKZCFRVTHJH-UHFFFAOYSA-N 0.000 claims 1
• 210000003608 fece Anatomy 0.000 claims 1
• 235000012208 gluconic acid Nutrition 0.000 claims 1
• 239000000174 gluconic acid Substances 0.000 claims 1
• 229940097043 glucuronic acid Drugs 0.000 claims 1
• 235000019382 gum benzoic Nutrition 0.000 claims 1
• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 claims 1
• 125000001041 indolyl group Chemical group 0.000 claims 1
• 229960003786 inosine Drugs 0.000 claims 1
• 125000001786 isothiazolyl group Chemical group 0.000 claims 1
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims 1
• RDXBZXWKSIEKKS-UHFFFAOYSA-N n-ethyldecan-1-amine Chemical compound CCCCCCCCCCNCC RDXBZXWKSIEKKS-UHFFFAOYSA-N 0.000 claims 1
• 125000003544 oxime group Chemical group 0.000 claims 1
• 125000002080 perylenyl group Chemical group C1(=CC=C2C=CC=C3C4=CC=CC5=CC=CC(C1=C23)=C45)* 0.000 claims 1
• CSHWQDPOILHKBI-UHFFFAOYSA-N peryrene Natural products C1=CC(C2=CC=CC=3C2=C2C=CC=3)=C3C2=CC=CC3=C1 CSHWQDPOILHKBI-UHFFFAOYSA-N 0.000 claims 1
• DBMHTLOVZSDLFD-UHFFFAOYSA-N piperidin-1-ylmethanamine Chemical compound NCN1CCCCC1 DBMHTLOVZSDLFD-UHFFFAOYSA-N 0.000 claims 1
• 125000000168 pyrrolyl group Chemical group 0.000 claims 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims 1
• 125000005493 quinolyl group Chemical group 0.000 claims 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims 1
• 230000001235 sensitizing effect Effects 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 69
• 241000710781 Flaviviridae Species 0.000 abstract description 5
• WRHZVMBBRYBTKZ-UHFFFAOYSA-N pyrrole-2-carboxylic acid Chemical compound OC(=O)C1=CC=CN1 WRHZVMBBRYBTKZ-UHFFFAOYSA-N 0.000 description 265
• DOYOPBSXEIZLRE-UHFFFAOYSA-N pyrrole-3-carboxylic acid Natural products OC(=O)C=1C=CNC=1 DOYOPBSXEIZLRE-UHFFFAOYSA-N 0.000 description 128
• 238000006243 chemical reaction Methods 0.000 description 77
• 239000011541 reaction mixture Substances 0.000 description 54
• XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
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• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• 239000002253 acid Substances 0.000 description 32
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 24
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
• 238000000034 method Methods 0.000 description 22
• 238000004128 high performance liquid chromatography Methods 0.000 description 21
• 239000007787 solid Substances 0.000 description 21
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 21
• 235000019439 ethyl acetate Nutrition 0.000 description 19
• 239000000243 solution Substances 0.000 description 19
• 125000003396 thiol group Chemical class [H]S* 0.000 description 19
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
• 238000009472 formulation Methods 0.000 description 18
• 238000005481 NMR spectroscopy Methods 0.000 description 16
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• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• 238000004458 analytical method Methods 0.000 description 15
• 239000007864 aqueous solution Substances 0.000 description 15
• 125000004104 aryloxy group Chemical group 0.000 description 15
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 15
• 238000011282 treatment Methods 0.000 description 15
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 14
• 210000004027 cell Anatomy 0.000 description 14
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