CA2450122C

CA2450122C - Novel heterocyclic antibacterial compounds

Novel heterocyclic antibacterial compounds Download PDF

Info

Publication number: CA2450122C
Authority: CA; Canada
Prior art keywords: compound; ethyl; oxo; hydrate; carboxy
Prior art date: 2001-06-15
Legal status : Expired - Fee Related

Application number

CA002450122A

Other languages

English (en)

French (fr)

Other versions

CA2450122A1 (en

Inventor

Chengxin Zhi

George E. Wright

Current Assignee

Microbiotix Inc

Original Assignee

Microbiotix Inc

Priority date

2001-06-15

Filing date

2002-06-17

Publication date

2009-10-20

2002-06-17 Application filed by Microbiotix Inc filed Critical Microbiotix Inc

2002-12-27 Publication of CA2450122A1 publication Critical patent/CA2450122A1/en

2009-10-20 Application granted granted Critical

2009-10-20 Publication of CA2450122C publication Critical patent/CA2450122C/en

2022-06-17 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 461
125000000623 heterocyclic group Chemical group 0.000 title abstract description 37
230000000844 anti-bacterial effect Effects 0.000 title description 15
-1 heterocyclic organic compounds Chemical class 0.000 claims abstract description 88
230000001580 bacterial effect Effects 0.000 claims abstract description 53
101710183280 Topoisomerase Proteins 0.000 claims abstract description 24
102000016928 DNA-directed DNA polymerase Human genes 0.000 claims abstract description 20
108020000946 Bacterial DNA Proteins 0.000 claims abstract description 12
150000003839 salts Chemical class 0.000 claims description 128
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 84
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical group O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 80
125000000217 alkyl group Chemical group 0.000 claims description 72
125000005843 halogen group Chemical group 0.000 claims description 67
238000000034 method Methods 0.000 claims description 51
125000001424 substituent group Chemical group 0.000 claims description 51
125000003118 aryl group Chemical group 0.000 claims description 49
229940035893 uracil Drugs 0.000 claims description 40
241000894006 Bacteria Species 0.000 claims description 29
125000003342 alkenyl group Chemical group 0.000 claims description 28
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
229920006395 saturated elastomer Polymers 0.000 claims description 27
239000003242 anti bacterial agent Substances 0.000 claims description 26
239000008194 pharmaceutical composition Substances 0.000 claims description 26
125000000304 alkynyl group Chemical group 0.000 claims description 25
208000035143 Bacterial infection Diseases 0.000 claims description 24
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 24
LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical group O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 23
241000894007 species Species 0.000 claims description 23
208000022362 bacterial infectious disease Diseases 0.000 claims description 21
230000003115 biocidal effect Effects 0.000 claims description 20
125000004429 atom Chemical group 0.000 claims description 18
241000192125 Firmicutes Species 0.000 claims description 17
XQCZBXHVTFVIFE-UHFFFAOYSA-N 2-amino-4-hydroxypyrimidine Chemical group NC1=NC=CC(O)=N1 XQCZBXHVTFVIFE-UHFFFAOYSA-N 0.000 claims description 16
230000000694 effects Effects 0.000 claims description 16
238000012360 testing method Methods 0.000 claims description 16
125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 14
230000002401 inhibitory effect Effects 0.000 claims description 13
108010014303 DNA-directed DNA polymerase Proteins 0.000 claims description 11
239000003814 drug Substances 0.000 claims description 11
108020004414 DNA Proteins 0.000 claims description 10
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 10
241000194033 Enterococcus Species 0.000 claims description 9
241000588724 Escherichia coli Species 0.000 claims description 9
238000011282 treatment Methods 0.000 claims description 9
241000193830 Bacillus <bacterium> Species 0.000 claims description 8
241000204031 Mycoplasma Species 0.000 claims description 8
241000191940 Staphylococcus Species 0.000 claims description 8
229940124307 fluoroquinolone Drugs 0.000 claims description 8
125000001054 5 membered carbocyclic group Chemical group 0.000 claims description 7
125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 7
241000193403 Clostridium Species 0.000 claims description 7
241000186781 Listeria Species 0.000 claims description 7
241000194017 Streptococcus Species 0.000 claims description 7
239000003937 drug carrier Substances 0.000 claims description 5
125000004193 piperazinyl group Chemical group 0.000 claims description 5
LYNNETNJMPHXJF-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C=3C(=CC(F)=CC=3)F)F)C(=O)C=2)=C1 LYNNETNJMPHXJF-UHFFFAOYSA-N 0.000 claims description 4
GAZAYHFWBIBZGV-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C(=O)C=2)=C1 GAZAYHFWBIBZGV-UHFFFAOYSA-N 0.000 claims description 4
CTTHOSAXMLPGMG-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[7-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]heptyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C(=O)C=2)=C1 CTTHOSAXMLPGMG-UHFFFAOYSA-N 0.000 claims description 4
FMNROQLLAZZFGR-UHFFFAOYSA-N 1-ethyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6,8-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4CC)=O)=CC=3F)F)C(=O)C=2)=C1 FMNROQLLAZZFGR-UHFFFAOYSA-N 0.000 claims description 4
BZULXVDYDGSWKC-UHFFFAOYSA-N 8-chloro-1-ethyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4CC)=O)=CC=3F)Cl)C(=O)C=2)=C1 BZULXVDYDGSWKC-UHFFFAOYSA-N 0.000 claims description 4
241000589517 Pseudomonas aeruginosa Species 0.000 claims description 4
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
241000293871 Salmonella enterica subsp. enterica serovar Typhi Species 0.000 claims description 4
241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 claims description 4
241000607764 Shigella dysenteriae Species 0.000 claims description 4
241000607626 Vibrio cholerae Species 0.000 claims description 4
230000001093 anti-cancer Effects 0.000 claims description 4
230000000840 anti-viral effect Effects 0.000 claims description 4
229940007046 shigella dysenteriae Drugs 0.000 claims description 4
229940118696 vibrio cholerae Drugs 0.000 claims description 4
UXYMMKYCPVNQBM-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4C=4C(=CC(F)=CC=4)F)=O)=CC=3F)OC)C(=O)C=2)=C1 UXYMMKYCPVNQBM-UHFFFAOYSA-N 0.000 claims description 3
BSSRCWTVYSAQCP-OAQYLSRUSA-N 1-cyclopropyl-7-[(3r)-4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]-3-methylpiperazin-1-yl]-6,8-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3[C@@H](CN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4C4CC4)=O)=CC=3F)F)C)C(=O)C=2)=C1 BSSRCWTVYSAQCP-OAQYLSRUSA-N 0.000 claims description 3
CFXOKKSZPDFENA-JOCHJYFZSA-N 1-cyclopropyl-7-[(3r)-4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]-3-methylpiperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3[C@@H](CN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C)C(=O)C=2)=C1 CFXOKKSZPDFENA-JOCHJYFZSA-N 0.000 claims description 3
BSSRCWTVYSAQCP-NRFANRHFSA-N 1-cyclopropyl-7-[(3s)-4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]-3-methylpiperazin-1-yl]-6,8-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3[C@H](CN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4C4CC4)=O)=CC=3F)F)C)C(=O)C=2)=C1 BSSRCWTVYSAQCP-NRFANRHFSA-N 0.000 claims description 3
CFXOKKSZPDFENA-QFIPXVFZSA-N 1-cyclopropyl-7-[(3s)-4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]-3-methylpiperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3[C@H](CN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C)C(=O)C=2)=C1 CFXOKKSZPDFENA-QFIPXVFZSA-N 0.000 claims description 3
YZACLCJBWPYSNU-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[2-[2-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]ethoxy]ethyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCOCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C(=O)C=2)=C1 YZACLCJBWPYSNU-UHFFFAOYSA-N 0.000 claims description 3
CMKWEZJDUBMWER-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[4-[6-(2,3-dihydro-1h-inden-5-ylamino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(N3CCN(CCCCN4C(NC(NC=5C=C6CCCC6=CC=5)=CC4=O)=O)CC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 CMKWEZJDUBMWER-UHFFFAOYSA-N 0.000 claims description 3
QMEXXOBVLGXEIR-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[4-[6-(3,4-dimethylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(C)=CC=C1NC(NC1=O)=CC(=O)N1CCCCN1CCN(C=2C(=CC=3C(=O)C(C(O)=O)=CN(C=3C=2)C2CC2)F)CC1 QMEXXOBVLGXEIR-UHFFFAOYSA-N 0.000 claims description 3
XHSSTBPTQHSWCP-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]-3-(hydroxymethyl)piperazin-1-yl]-6,8-difluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3C(CN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4C4CC4)=O)=CC=3F)F)CO)C(=O)C=2)=C1 XHSSTBPTQHSWCP-UHFFFAOYSA-N 0.000 claims description 3
FVRJICZSAASHOD-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C=C4C(C(C(C(O)=O)=CN4C4CC4)=O)=CC=3)C(=O)C=2)=C1 FVRJICZSAASHOD-UHFFFAOYSA-N 0.000 claims description 3
IDHYRQSMSDNNHK-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[4-[6-[(3,4-dichlorophenyl)methylamino]-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C12=CC(N3CCN(CCCCN4C(NC(NCC=5C=C(Cl)C(Cl)=CC=5)=CC4=O)=O)CC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 IDHYRQSMSDNNHK-UHFFFAOYSA-N 0.000 claims description 3
LGKFWTBHZUFRPF-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C(=O)C=2)=C1 LGKFWTBHZUFRPF-UHFFFAOYSA-N 0.000 claims description 3
AZLODONDCTYFJR-UHFFFAOYSA-N 1-cyclopropyl-7-[6-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]-2,3,4a,5,7,7a-hexahydropyrrolo[3,4-b][1,4]oxazin-4-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CC4N(CCOC4C3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C(=O)C=2)=C1 AZLODONDCTYFJR-UHFFFAOYSA-N 0.000 claims description 3
YYQUTMPTKZCVJC-UHFFFAOYSA-N 1-ethyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(CC)C=4N=3)F)C(=O)C=2)=C1 YYQUTMPTKZCVJC-UHFFFAOYSA-N 0.000 claims description 3
CITJFDZQCOBOGW-UHFFFAOYSA-N 1-ethyl-7-[4-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]piperazin-1-yl]-6-fluoro-4-oxo-1,8-naphthyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(CC)C=4N=3)F)C(=O)C=2)=C1 CITJFDZQCOBOGW-UHFFFAOYSA-N 0.000 claims description 3
CHUPOJRARUNHOV-UHFFFAOYSA-N 1-ethyl-7-[6-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]-3,4,4a,5,7,7a-hexahydro-2h-pyrrolo[3,4-b]pyridin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CC4N(CCCC4C3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(CC)C=4C=3)F)C(=O)C=2)=C1 CHUPOJRARUNHOV-UHFFFAOYSA-N 0.000 claims description 3
DSNJMIBRKYIWGB-UHFFFAOYSA-N 7-[4-[4-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]butyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C(=O)C=2)=C1 DSNJMIBRKYIWGB-UHFFFAOYSA-N 0.000 claims description 3
RICAYQWOHSLBTP-UHFFFAOYSA-N 7-[4-[4-[6-(3-chloro-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(Cl)C(C)=CC=C1NC(NC1=O)=CC(=O)N1CCCCN1CCN(C=2C(=CC=3C(=O)C(C(O)=O)=CN(C=3C=2)C2CC2)F)CC1 RICAYQWOHSLBTP-UHFFFAOYSA-N 0.000 claims description 3
YGLSEVNIFPZVJH-UHFFFAOYSA-N 7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-1-(2-hydroxyethyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(CCO)C=4C=3)F)C(=O)C=2)=C1 YGLSEVNIFPZVJH-UHFFFAOYSA-N 0.000 claims description 3
PXGPMQZETUARJW-UHFFFAOYSA-N 7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-1-(4-fluorophenyl)-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C=3C=CC(F)=CC=3)F)C(=O)C=2)=C1 PXGPMQZETUARJW-UHFFFAOYSA-N 0.000 claims description 3
KDPDHQQFMFWGKJ-UHFFFAOYSA-N 8-ethyl-2-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-5-oxopyrido[2,3-d]pyrimidine-6-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3N=C4C(C(C(C(O)=O)=CN4CC)=O)=CN=3)C(=O)C=2)=C1 KDPDHQQFMFWGKJ-UHFFFAOYSA-N 0.000 claims description 3
FKKVBJQNRRLLLI-UHFFFAOYSA-N ethyl 1-cyclopropyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(N3CCN(CCCCN4C(NC(NC=5C=C(CC)C(C)=CC=5)=CC4=O)=O)CC3)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1CC1 FKKVBJQNRRLLLI-UHFFFAOYSA-N 0.000 claims description 3
LUQOUUAOECRQJZ-UHFFFAOYSA-N ethyl 7-[4-[4-(6-anilino-2,4-dioxo-1h-pyrimidin-3-yl)butyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(N3CCN(CCCCN4C(NC(NC=5C=CC=CC=5)=CC4=O)=O)CC3)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1CC1 LUQOUUAOECRQJZ-UHFFFAOYSA-N 0.000 claims description 3
MXDPVSQCZYGRSO-UHFFFAOYSA-N ethyl 7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6,8-difluoro-1-(2-hydroxyethyl)-4-oxoquinoline-3-carboxylate Chemical compound FC=1C=C2C(=O)C(C(=O)OCC)=CN(CCO)C2=C(F)C=1N(CC1)CCN1CCCCN(C(N1)=O)C(=O)C=C1NC1=CC=C(C)C(CC)=C1 MXDPVSQCZYGRSO-UHFFFAOYSA-N 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
229910021654 trace metal Inorganic materials 0.000 claims description 3
239000011782 vitamin Substances 0.000 claims description 3
235000013343 vitamin Nutrition 0.000 claims description 3
229940088594 vitamin Drugs 0.000 claims description 3
229930003231 vitamin Natural products 0.000 claims description 3
KTJZQGHYOHXLBR-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-6-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)C=3C(=CC(F)=CC=3)F)C(=O)C=2)=C1 KTJZQGHYOHXLBR-UHFFFAOYSA-N 0.000 claims description 2
NRSODYKCKMVMJO-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-6-[4-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]piperazin-1-yl]-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)C=3C(=CC(F)=CC=3)F)C(=O)C=2)=C1 NRSODYKCKMVMJO-UHFFFAOYSA-N 0.000 claims description 2
RLTJVACKEUKLJE-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-7-[[1-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]pyrrolidin-3-yl]methylamino]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CC(CNC=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C=4C(=CC(F)=CC=4)F)F)CC3)C(=O)C=2)=C1 RLTJVACKEUKLJE-UHFFFAOYSA-N 0.000 claims description 2
BQUBBSOIYZBBOF-UHFFFAOYSA-N 1-(2,4-difluorophenyl)-7-[[1-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]pyrrolidin-3-yl]methylamino]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CC(CNC=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C=4C(=CC(F)=CC=4)F)F)CC3)C(=O)C=2)=C1 BQUBBSOIYZBBOF-UHFFFAOYSA-N 0.000 claims description 2
UMGNOHAHBVFFSE-UHFFFAOYSA-N 1-cyclopropyl-6-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)C3CC3)C(=O)C=2)=C1 UMGNOHAHBVFFSE-UHFFFAOYSA-N 0.000 claims description 2
ATKRMHKKVKSKDD-UHFFFAOYSA-N 1-cyclopropyl-6-[4-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]piperazin-1-yl]-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)C3CC3)C(=O)C=2)=C1 ATKRMHKKVKSKDD-UHFFFAOYSA-N 0.000 claims description 2
TUAVKZURGLLRHQ-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4C4CC4)=O)=CC=3F)OC)C(=O)C=2)=C1 TUAVKZURGLLRHQ-UHFFFAOYSA-N 0.000 claims description 2
LXGXEOHIPBURNU-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[4-[6-(3-ethylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound CCC1=CC=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C3CC3)F)C(=O)C=2)=C1 LXGXEOHIPBURNU-UHFFFAOYSA-N 0.000 claims description 2
FYGWDABKQRNMHR-UHFFFAOYSA-N 1-cyclopropyl-7-[4-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]piperazin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CCN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4C4CC4)=O)=CC=3F)OC)C(=O)C=2)=C1 FYGWDABKQRNMHR-UHFFFAOYSA-N 0.000 claims description 2
CJOGUVFCFDFESU-UHFFFAOYSA-N 1-cyclopropyl-7-[[1-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]pyrrolidin-3-yl]methylamino]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CC(CNC=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)CC3)C(=O)C=2)=C1 CJOGUVFCFDFESU-UHFFFAOYSA-N 0.000 claims description 2
AVPRGYSVYCJALJ-UHFFFAOYSA-N 1-ethyl-6-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)CC)C(=O)C=2)=C1 AVPRGYSVYCJALJ-UHFFFAOYSA-N 0.000 claims description 2
CEEMTVQVNKSSHX-UHFFFAOYSA-N 1-ethyl-6-[4-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]piperazin-1-yl]-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)CC)C(=O)C=2)=C1 CEEMTVQVNKSSHX-UHFFFAOYSA-N 0.000 claims description 2
NNTJRXFQKMHWCH-UHFFFAOYSA-N 1-ethyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(CC)C=4C=3)F)C(=O)C=2)=C1 NNTJRXFQKMHWCH-UHFFFAOYSA-N 0.000 claims description 2
MDURNWAMSWGJEK-UHFFFAOYSA-N 1-ethyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4CC)=O)=CC=3F)OC)C(=O)C=2)=C1 MDURNWAMSWGJEK-UHFFFAOYSA-N 0.000 claims description 2
JNBOWSQHZLVSPW-UHFFFAOYSA-N 1-ethyl-7-[4-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]piperazin-1-yl]-6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CCN(CC3)C=3C(=C4C(C(C(C(O)=O)=CN4CC)=O)=CC=3F)OC)C(=O)C=2)=C1 JNBOWSQHZLVSPW-UHFFFAOYSA-N 0.000 claims description 2
UDNFCWDKRJCZNT-UHFFFAOYSA-N 1-ethyl-7-[[1-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]pyrrolidin-3-yl]methylamino]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CC(CNC=4C(=CC=5C(=O)C(C(O)=O)=CN(CC)C=5C=4)F)CC3)C(=O)C=2)=C1 UDNFCWDKRJCZNT-UHFFFAOYSA-N 0.000 claims description 2
OEQDQOSPNTWRNH-UHFFFAOYSA-N 1-ethyl-7-[[1-[5-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]pentyl]pyrrolidin-3-yl]methylamino]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCCN3CC(CNC=4C(=CC=5C(=O)C(C(O)=O)=CN(CC)C=5C=4)F)CC3)C(=O)C=2)=C1 OEQDQOSPNTWRNH-UHFFFAOYSA-N 0.000 claims description 2
FEMMPNIZRNDXHL-UHFFFAOYSA-N 1-tert-butyl-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(O)=O)=CN(C=4C=3)C(C)(C)C)F)C(=O)C=2)=C1 FEMMPNIZRNDXHL-UHFFFAOYSA-N 0.000 claims description 2
SVTYDZIOECJVDC-UHFFFAOYSA-N 6-[4-[4-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]butyl]piperazin-1-yl]-1-(2,4-difluorophenyl)-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)C=3C(=CC(F)=CC=3)F)C(=O)C=2)=C1 SVTYDZIOECJVDC-UHFFFAOYSA-N 0.000 claims description 2
ZEEGKCFKHLONIM-UHFFFAOYSA-N 6-[4-[4-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]butyl]piperazin-1-yl]-1-cyclopropyl-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)C3CC3)C(=O)C=2)=C1 ZEEGKCFKHLONIM-UHFFFAOYSA-N 0.000 claims description 2
RMBPDIADTSBGNY-UHFFFAOYSA-N 6-[4-[4-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]butyl]piperazin-1-yl]-1-ethyl-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)CC)C(=O)C=2)=C1 RMBPDIADTSBGNY-UHFFFAOYSA-N 0.000 claims description 2
PYCIDWKKEFYZEG-UHFFFAOYSA-N 6-[4-[5-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]pentyl]piperazin-1-yl]-1-(2,4-difluorophenyl)-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)C=3C(=CC(F)=CC=3)F)C(=O)C=2)=C1 PYCIDWKKEFYZEG-UHFFFAOYSA-N 0.000 claims description 2
DCXICMDGPZOXDJ-UHFFFAOYSA-N 6-[4-[5-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]pentyl]piperazin-1-yl]-1-cyclopropyl-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)C3CC3)C(=O)C=2)=C1 DCXICMDGPZOXDJ-UHFFFAOYSA-N 0.000 claims description 2
PQOFAMODAHPWEP-UHFFFAOYSA-N 6-[4-[5-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]pentyl]piperazin-1-yl]-1-ethyl-4-oxopyridine-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCCN3CCN(CC3)C=3N(C=C(C(=O)C=3)C(O)=O)CC)C(=O)C=2)=C1 PQOFAMODAHPWEP-UHFFFAOYSA-N 0.000 claims description 2
FRPWOBGYZSPBNV-UHFFFAOYSA-N 7-[[1-[4-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]butyl]pyrrolidin-3-yl]methylamino]-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCN3CC(CNC=4C(=CC=5C(=O)C(C(O)=O)=CN(CC)C=5C=4)F)CC3)C(=O)C=2)=C1 FRPWOBGYZSPBNV-UHFFFAOYSA-N 0.000 claims description 2
SMRKBFJFYKOAOU-UHFFFAOYSA-N 7-[[1-[5-[2-amino-4-(3-ethyl-4-methylanilino)-6-oxopyrimidin-1-yl]pentyl]pyrrolidin-3-yl]methylamino]-1-ethyl-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2N=C(N)N(CCCCCN3CC(CNC=4C(=CC=5C(=O)C(C(O)=O)=CN(CC)C=5C=4)F)CC3)C(=O)C=2)=C1 SMRKBFJFYKOAOU-UHFFFAOYSA-N 0.000 claims description 2
HZEJLWYMAOTFKR-UHFFFAOYSA-N benzyl 1-cyclopropyl-7-[4-[2-[2-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]ethoxy]ethyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCOCCN3CCN(CC3)C=3C(=CC=4C(=O)C(C(=O)OCC=5C=CC=CC=5)=CN(C=4C=3)C3CC3)F)C(=O)C=2)=C1 HZEJLWYMAOTFKR-UHFFFAOYSA-N 0.000 claims description 2
RRSYMSXWWHOVFQ-UHFFFAOYSA-N ethyl 1-(2,4-difluorophenyl)-7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(N3CCN(CCCCN4C(NC(NC=5C=C(CC)C(C)=CC=5)=CC4=O)=O)CC3)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1=CC=C(F)C=C1F RRSYMSXWWHOVFQ-UHFFFAOYSA-N 0.000 claims description 2
SSMJIEZQNHZSKK-UHFFFAOYSA-N ethyl 7-[4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]piperazin-1-yl]-6-fluoro-1-(4-fluorophenyl)-4-oxoquinoline-3-carboxylate Chemical compound C12=CC(N3CCN(CCCCN4C(NC(NC=5C=C(CC)C(C)=CC=5)=CC4=O)=O)CC3)=C(F)C=C2C(=O)C(C(=O)OCC)=CN1C1=CC=C(F)C=C1 SSMJIEZQNHZSKK-UHFFFAOYSA-N 0.000 claims description 2
239000001963 growth medium Substances 0.000 claims description 2
150000003722 vitamin derivatives Chemical class 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims 4
230000001603 reducing effect Effects 0.000 claims 4
QSAAHDHQCXWFQZ-UHFFFAOYSA-N 1-cyclopropyl-7-[[1-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1h-pyrimidin-3-yl]butyl]pyrrolidin-3-yl]methylamino]-6-fluoro-4-oxoquinoline-3-carboxylic acid Chemical compound C1=C(C)C(CC)=CC(NC=2NC(=O)N(CCCCN3CC(CNC=4C(=CC=5C(=O)C(C(O)=O)=CN(C=5C=4)C4CC4)F)CC3)C(=O)C=2)=C1 QSAAHDHQCXWFQZ-UHFFFAOYSA-N 0.000 claims 1
FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical group CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 claims 1
238000003786 synthesis reaction Methods 0.000 abstract description 32
230000015572 biosynthetic process Effects 0.000 abstract description 29
239000000543 intermediate Substances 0.000 abstract description 29
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 225
239000000203 mixture Substances 0.000 description 127
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 106
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 84
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 72
239000007787 solid Substances 0.000 description 64
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HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 52
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239000000243 solution Substances 0.000 description 50
229910052739 hydrogen Inorganic materials 0.000 description 38
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 36
229910052799 carbon Inorganic materials 0.000 description 32
229910052757 nitrogen Inorganic materials 0.000 description 31
238000005160 1H NMR spectroscopy Methods 0.000 description 30
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
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239000003480 eluent Substances 0.000 description 30
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239000002585 base Substances 0.000 description 28
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 27
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 27
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 26
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
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HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
150000002148 esters Chemical class 0.000 description 24
229910052717 sulfur Inorganic materials 0.000 description 23
UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical class O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 22
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 22
239000000725 suspension Substances 0.000 description 20
125000003545 alkoxy group Chemical group 0.000 description 19
125000003282 alkyl amino group Chemical group 0.000 description 19
239000000047 product Substances 0.000 description 19
238000005481 NMR spectroscopy Methods 0.000 description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
150000004985 diamines Chemical class 0.000 description 17
125000005842 heteroatom Chemical group 0.000 description 17
229940088710 antibiotic agent Drugs 0.000 description 16
238000004587 chromatography analysis Methods 0.000 description 16
208000015181 infectious disease Diseases 0.000 description 16
230000002829 reductive effect Effects 0.000 description 16
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
239000002777 nucleoside Substances 0.000 description 15
229910000027 potassium carbonate Inorganic materials 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
241000699670 Mus sp. Species 0.000 description 14
150000003833 nucleoside derivatives Chemical class 0.000 description 14
125000006239 protecting group Chemical group 0.000 description 14
125000002252 acyl group Chemical group 0.000 description 13
125000004093 cyano group Chemical group *C#N 0.000 description 13
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 13
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
235000017557 sodium bicarbonate Nutrition 0.000 description 13
229910000030 sodium bicarbonate Inorganic materials 0.000 description 13
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 12
229940125782 compound 2 Drugs 0.000 description 12
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 12
102000004190 Enzymes Human genes 0.000 description 11
108090000790 Enzymes Proteins 0.000 description 11
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
125000002837 carbocyclic group Chemical group 0.000 description 11
125000000753 cycloalkyl group Chemical group 0.000 description 11
239000000843 powder Substances 0.000 description 11
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
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