ZA200208271B - Chromenylmethyl pyrimidinediamines as antibacterial agents. - Google Patents

Chromenylmethyl pyrimidinediamines as antibacterial agents. Download PDF

Info

Publication number: ZA200208271B
Authority: ZA; South Africa
Prior art keywords: dimethyl; chromen; ylmethyl; methoxy; compound
Prior art date: 2000-04-27

Application number

ZA200208271A

Other languages

English (en)

Inventor

Peter Mohr

Philippe Pflieger

Original Assignee

Basilea Pharmaceutica Ag

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-04-27

Filing date

2002-10-14

Publication date

2004-01-26

2002-10-14 Application filed by Basilea Pharmaceutica Ag filed Critical Basilea Pharmaceutica Ag

2004-01-26 Publication of ZA200208271B publication Critical patent/ZA200208271B/en

Links

YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical class NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 title description 3
239000003242 anti bacterial agent Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 96
150000003839 salts Chemical class 0.000 claims abstract description 26
238000004519 manufacturing process Methods 0.000 claims abstract description 17
239000003814 drug Substances 0.000 claims abstract description 15
239000000126 substance Substances 0.000 claims abstract description 13
150000008371 chromenes Chemical class 0.000 claims abstract description 3
-1 p-tolylsulfonyloxy Chemical group 0.000 claims description 40
238000000034 method Methods 0.000 claims description 18
229910052794 bromium Inorganic materials 0.000 claims description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 15
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
125000001072 heteroaryl group Chemical group 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 9
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 8
125000003118 aryl group Chemical group 0.000 claims description 8
239000000203 mixture Substances 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
125000000623 heterocyclic group Chemical group 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
208000035473 Communicable disease Diseases 0.000 claims description 5
125000002837 carbocyclic group Chemical group 0.000 claims description 5
229910052799 carbon Inorganic materials 0.000 claims description 5
125000000524 functional group Chemical group 0.000 claims description 5
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 5
125000006239 protecting group Chemical group 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 4
125000004414 alkyl thio group Chemical group 0.000 claims description 4
125000000304 alkynyl group Chemical group 0.000 claims description 4
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
150000004985 diamines Chemical class 0.000 claims description 4
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 claims description 4
229940124530 sulfonamide Drugs 0.000 claims description 4
AWSAHGFHUQXPIF-UHFFFAOYSA-N 5-[(4-bromo-8-ethoxyspiro[chromene-2,1'-cyclobutane]-6-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=1C=2C(Br)=CC3(CCC3)OC=2C(OCC)=CC=1CC1=CN=C(N)N=C1N AWSAHGFHUQXPIF-UHFFFAOYSA-N 0.000 claims description 3
SWJJNJQGSMROBJ-UHFFFAOYSA-N 5-[(8-ethoxy-2,2,4-trimethylchromen-6-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=1C=2C(C)=CC(C)(C)OC=2C(OCC)=CC=1CC1=CN=C(N)N=C1N SWJJNJQGSMROBJ-UHFFFAOYSA-N 0.000 claims description 3
XXUYEERDOBVMTA-UHFFFAOYSA-N 5-[(8-ethoxy-2,2-dimethyl-4-propylchromen-6-yl)methyl]pyrimidine-2,4-diamine Chemical compound C1=C2C(CCC)=CC(C)(C)OC2=C(OCC)C=C1CC1=CN=C(N)N=C1N XXUYEERDOBVMTA-UHFFFAOYSA-N 0.000 claims description 3
RICKLMXZWGPFEH-UHFFFAOYSA-N 5-[(8-ethoxy-4-ethyl-2,2-dimethylchromen-6-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=1C=2C(CC)=CC(C)(C)OC=2C(OCC)=CC=1CC1=CN=C(N)N=C1N RICKLMXZWGPFEH-UHFFFAOYSA-N 0.000 claims description 3
DSDHQJZBYGTHTE-UHFFFAOYSA-N 5-[[8-methoxy-4-(3-methoxyprop-1-ynyl)-2,2-dimethylchromen-6-yl]methyl]pyrimidine-2,4-diamine Chemical compound C1=C2C(C#CCOC)=CC(C)(C)OC2=C(OC)C=C1CC1=CN=C(N)N=C1N DSDHQJZBYGTHTE-UHFFFAOYSA-N 0.000 claims description 3
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 3
150000001721 carbon Chemical group 0.000 claims description 3
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
125000004665 trialkylsilyl group Chemical group 0.000 claims description 3
KCEXTTYEVBQAAE-UHFFFAOYSA-N 5-[(4-bromo-8-methoxyspiro[chromene-2,4'-oxane]-6-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=1C=2C(Br)=CC3(CCOCC3)OC=2C(OC)=CC=1CC1=CN=C(N)N=C1N KCEXTTYEVBQAAE-UHFFFAOYSA-N 0.000 claims description 2
VSJGJTFTPPQZRO-UHFFFAOYSA-N 5-[(4-chloro-8-methoxy-2,2-dimethylchromen-6-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=1C=2C(Cl)=CC(C)(C)OC=2C(OC)=CC=1CC1=CN=C(N)N=C1N VSJGJTFTPPQZRO-UHFFFAOYSA-N 0.000 claims description 2
UXGWEACVEQDIIR-UHFFFAOYSA-N 5-[(8-methoxy-2,2-dimethyl-4-methylsulfanylchromen-6-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=1C=2C(SC)=CC(C)(C)OC=2C(OC)=CC=1CC1=CN=C(N)N=C1N UXGWEACVEQDIIR-UHFFFAOYSA-N 0.000 claims description 2
LOUYGYYLVYMECR-UHFFFAOYSA-N 5-[[4-(4-fluorophenyl)-8-methoxy-2,2-dimethylchromen-6-yl]methyl]pyrimidine-2,4-diamine Chemical compound C=1C=2C(C=3C=CC(F)=CC=3)=CC(C)(C)OC=2C(OC)=CC=1CC1=CN=C(N)N=C1N LOUYGYYLVYMECR-UHFFFAOYSA-N 0.000 claims description 2
125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims description 2
125000005016 hydroxyalkynyl group Chemical group 0.000 claims description 2
238000011321 prophylaxis Methods 0.000 claims description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
241001465754 Metazoa Species 0.000 claims 2
230000000069 prophylactic effect Effects 0.000 claims 2
230000001225 therapeutic effect Effects 0.000 claims 2
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
239000002253 acid Substances 0.000 abstract description 21
239000000543 intermediate Substances 0.000 abstract description 17
150000003456 sulfonamides Chemical class 0.000 abstract description 6
239000013543 active substance Substances 0.000 abstract description 3
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 96
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 78
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 58
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 56
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 49
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 46
239000013078 crystal Substances 0.000 description 46
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 46
229960001760 dimethyl sulfoxide Drugs 0.000 description 44
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
229910052943 magnesium sulfate Inorganic materials 0.000 description 39
235000019341 magnesium sulphate Nutrition 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 35
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
239000012267 brine Substances 0.000 description 33
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
238000003818 flash chromatography Methods 0.000 description 31
239000002904 solvent Substances 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 26
238000001704 evaporation Methods 0.000 description 25
230000008020 evaporation Effects 0.000 description 25
239000000460 chlorine Substances 0.000 description 24
238000001035 drying Methods 0.000 description 24
238000005406 washing Methods 0.000 description 24
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 23
235000002639 sodium chloride Nutrition 0.000 description 23
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
238000000605 extraction Methods 0.000 description 21
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 20
239000003921 oil Substances 0.000 description 20
235000019198 oils Nutrition 0.000 description 20
239000007787 solid Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
239000012043 crude product Substances 0.000 description 14
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
239000012300 argon atmosphere Substances 0.000 description 12
229960000789 guanidine hydrochloride Drugs 0.000 description 12
PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 12
FENJKTQEFUPECW-UHFFFAOYSA-N 3-anilinopropanenitrile Chemical compound N#CCCNC1=CC=CC=C1 FENJKTQEFUPECW-UHFFFAOYSA-N 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
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 10
150000001241 acetals Chemical class 0.000 description 10
238000004817 gas chromatography Methods 0.000 description 10
239000002585 base Substances 0.000 description 9
239000012039 electrophile Substances 0.000 description 9
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
239000012876 carrier material Substances 0.000 description 8
229910052801 chlorine Inorganic materials 0.000 description 8
238000002425 crystallisation Methods 0.000 description 8
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 8
239000012044 organic layer Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
239000000243 solution Substances 0.000 description 8
239000007858 starting material Substances 0.000 description 8
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 7
108010022394 Threonine synthase Proteins 0.000 description 7
150000001299 aldehydes Chemical class 0.000 description 7
230000000844 anti-bacterial effect Effects 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
102000004419 dihydrofolate reductase Human genes 0.000 description 7
239000011737 fluorine Substances 0.000 description 7
229910052731 fluorine Inorganic materials 0.000 description 7
WPYBRGOPUWRINE-UHFFFAOYSA-N 4-bromo-6-(1,3-dioxolan-2-yl)-8-ethoxy-2,2-dimethylchromene Chemical compound C=1C=2C(Br)=CC(C)(C)OC=2C(OCC)=CC=1C1OCCO1 WPYBRGOPUWRINE-UHFFFAOYSA-N 0.000 description 6
INLHTZSEHJMMLW-UHFFFAOYSA-N 4-bromo-6-(1,3-dioxolan-2-yl)-8-methoxy-2,2-dimethylchromene Chemical compound C=1C=2C(Br)=CC(C)(C)OC=2C(OC)=CC=1C1OCCO1 INLHTZSEHJMMLW-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
125000003545 alkoxy group Chemical group 0.000 description 6
230000008025 crystallization Effects 0.000 description 6
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 6
MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 5
FBBCSYADXYILEH-UHFFFAOYSA-N 4-hydroxy-3-iodo-5-methoxybenzaldehyde Chemical compound COC1=CC(C=O)=CC(I)=C1O FBBCSYADXYILEH-UHFFFAOYSA-N 0.000 description 5
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 5
125000005236 alkanoylamino group Chemical group 0.000 description 5
125000004466 alkoxycarbonylamino group Chemical group 0.000 description 5
125000001246 bromo group Chemical group Br* 0.000 description 5
238000001816 cooling Methods 0.000 description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 5
239000003960 organic solvent Substances 0.000 description 5
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 5
AYEKOFBPNLCAJY-UHFFFAOYSA-O thiamine pyrophosphate Chemical compound CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N AYEKOFBPNLCAJY-UHFFFAOYSA-O 0.000 description 5
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
WFAHCDLEWJKPJS-UHFFFAOYSA-N 3-ethoxy-4-hydroxy-5-iodobenzaldehyde Chemical compound CCOC1=CC(C=O)=CC(I)=C1O WFAHCDLEWJKPJS-UHFFFAOYSA-N 0.000 description 4
ONKWEGUKYJSTJW-UHFFFAOYSA-N 4-bromo-8-methoxy-2,2-dimethylchromene-6-carbaldehyde Chemical compound BrC1=CC(C)(C)OC2=C1C=C(C=O)C=C2OC ONKWEGUKYJSTJW-UHFFFAOYSA-N 0.000 description 4
239000001828 Gelatine Substances 0.000 description 4
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
241000191967 Staphylococcus aureus Species 0.000 description 4
241000193998 Streptococcus pneumoniae Species 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 4
239000002775 capsule Substances 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
229920000159 gelatin Polymers 0.000 description 4
235000019322 gelatine Nutrition 0.000 description 4
239000007788 liquid Substances 0.000 description 4
229920005862 polyol Polymers 0.000 description 4
150000003077 polyols Chemical class 0.000 description 4
229940031000 streptococcus pneumoniae Drugs 0.000 description 4
229960005404 sulfamethoxazole Drugs 0.000 description 4
JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 4
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 3
JQGKGZPSTIGWGQ-UHFFFAOYSA-N 4-bromo-8-ethoxy-2,2-dimethylchromene-6-carbaldehyde Chemical compound BrC1=CC(C)(C)OC2=C1C=C(C=O)C=C2OCC JQGKGZPSTIGWGQ-UHFFFAOYSA-N 0.000 description 3
LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 3
KITPJENAFLVONE-UHFFFAOYSA-N 8-ethoxy-4-(2-hydroxypropan-2-yl)-2,2-dimethylchromene-6-carbaldehyde Chemical compound CC(O)(C)C1=CC(C)(C)OC2=C1C=C(C=O)C=C2OCC KITPJENAFLVONE-UHFFFAOYSA-N 0.000 description 3
UMPRIBRTTYVHCK-UHFFFAOYSA-N 8-methoxy-2,2,4-trimethylchromene-6-carbaldehyde Chemical compound CC1=CC(C)(C)OC2=C1C=C(C=O)C=C2OC UMPRIBRTTYVHCK-UHFFFAOYSA-N 0.000 description 3
IRMONAYMIVIKDK-UHFFFAOYSA-N 8-methoxy-2,2-dimethylchromene-6-carbaldehyde Chemical compound C1=CC(C)(C)OC2=C1C=C(C=O)C=C2OC IRMONAYMIVIKDK-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
238000006069 Suzuki reaction reaction Methods 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000007859 condensation product Substances 0.000 description 3
230000008878 coupling Effects 0.000 description 3
239000007819 coupling partner Substances 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
239000006260 foam Substances 0.000 description 3
238000007306 functionalization reaction Methods 0.000 description 3
229960004198 guanidine Drugs 0.000 description 3
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
239000010410 layer Substances 0.000 description 3
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 3
238000007911 parenteral administration Methods 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
239000011591 potassium Substances 0.000 description 3
238000000926 separation method Methods 0.000 description 3
229910000104 sodium hydride Inorganic materials 0.000 description 3
238000003756 stirring Methods 0.000 description 3
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235000011149 sulphuric acid Nutrition 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
LUVVTOXUZHPHLA-UHFFFAOYSA-N tert-butyl 4-(4-cyanophenyl)-6-[(2,4-diaminopyrimidin-5-yl)methyl]-8-ethoxyspiro[chromene-2,4'-piperidine]-1'-carboxylate Chemical compound C=1C=2C(C=3C=CC(=CC=3)C#N)=CC3(CCN(CC3)C(=O)OC(C)(C)C)OC=2C(OCC)=CC=1CC1=CN=C(N)N=C1N LUVVTOXUZHPHLA-UHFFFAOYSA-N 0.000 description 1
WBTGCIUVHXADGH-UHFFFAOYSA-N tert-butyl 6-formyl-8-methoxyspiro[chromene-2,4'-piperidine]-1'-carboxylate Chemical compound O1C=2C(OC)=CC(C=O)=CC=2C=CC21CCN(C(=O)OC(C)(C)C)CC2 WBTGCIUVHXADGH-UHFFFAOYSA-N 0.000 description 1
UCKGFQVBALEERS-UHFFFAOYSA-N tert-butyl 8-ethoxy-6-formylspiro[chromene-2,4'-piperidine]-1'-carboxylate Chemical compound O1C=2C(OCC)=CC(C=O)=CC=2C=CC21CCN(C(=O)OC(C)(C)C)CC2 UCKGFQVBALEERS-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000001984 thiazolidinyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
125000002053 thietanyl group Chemical group 0.000 description 1
125000001730 thiiranyl group Chemical group 0.000 description 1
125000004568 thiomorpholinyl group Chemical group 0.000 description 1
ARYHTUPFQTUBBG-UHFFFAOYSA-N thiophen-2-ylboronic acid Chemical compound OB(O)C1=CC=CS1 ARYHTUPFQTUBBG-UHFFFAOYSA-N 0.000 description 1
QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
229940086542 triethylamine Drugs 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
229960001082 trimethoprim Drugs 0.000 description 1
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000001291 vacuum drying Methods 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
229910052727 yttrium Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- 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
- A61P31/04—Antibacterial agents
- 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
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic System
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/0803—Compounds with Si-C or Si-Si linkages
- C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
- C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring
- C07F7/0814—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring said ring is substituted at a C ring atom by Si

ZA200208271A 2000-04-27 2002-10-14 Chromenylmethyl pyrimidinediamines as antibacterial agents. ZA200208271B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
EP00108945		2000-04-27

Publications (1)

Publication Number	Publication Date
ZA200208271B true ZA200208271B (en)	2004-01-26

Family

ID=8168565

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ZA200208271A ZA200208271B (en)	2000-04-27	2002-10-14	Chromenylmethyl pyrimidinediamines as antibacterial agents.

Country Status (14)

Country	Link
US (1)	US6818649B2 (ko)
EP (1)	EP1278742B1 (ko)
JP (1)	JP4033676B2 (ko)
KR (1)	KR20020093966A (ko)
CN (1)	CN1249057C (ko)
AT (1)	ATE284882T1 (ko)
AU (1)	AU2001252269A1 (ko)
BR (1)	BR0110255A (ko)
CA (1)	CA2405614A1 (ko)
DE (1)	DE60107832T2 (ko)
ES (1)	ES2232614T3 (ko)
MX (1)	MXPA02010518A (ko)
WO (1)	WO2001083476A1 (ko)
ZA (1)	ZA200208271B (ko)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
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TWI243173B (en)	1999-11-17	2005-11-11	Akzo Nobel Nv	Spiro[2H-1-benzopyran-2,4'-piperidine] derivatives
AU2004278414B2 (en) *	2003-10-01	2012-05-24	Adolor Corporation	Spirocyclic heterocyclic derivatives and methods of their use
ATE451381T1 (de) *	2005-01-19	2009-12-15	Rigel Pharmaceuticals Inc	Prodrugs aus 2,4-pyrimidindiamin-verbindungen und ihre verwendungen
US7598261B2 (en)	2005-03-31	2009-10-06	Adolor Corporation	Spirocyclic heterocyclic derivatives and methods of their use
EP1770089A1 (en) *	2005-10-03	2007-04-04	Institut Pasteur	Pyranodibenzofuran derivatives with antifungal and antibacterial activity
US7855194B2 (en)	2006-03-27	2010-12-21	Hoffmann-La Roche Inc.	Pyrimidine, quinazoline, pteridine and triazine derivatives
US7576207B2 (en)	2006-04-06	2009-08-18	Adolor Corporation	Spirocyclic heterocyclic derivatives and methods of their use
CN109134493A (zh) *	2018-09-19	2019-01-04	浙江师范大学	一种具有抗菌活性的2-氧代色烯并噻吩衍生物及其合成方法和应用
CN109988156B (zh) *	2019-03-12	2021-12-28	广东中科药物研究有限公司	一种氨基嘧啶化合物
CN112824412B (zh) *	2019-11-21	2022-09-16	中国科学院大连化学物理研究所	手性1′H-螺[吲哚啉-3,4′-吡喃并[2,3-c]吡唑]-2-酮类化合物

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WO1997020839A1 (en) *	1995-12-04	1997-06-12	F. Hoffmann-La Roche Ag	Diaminopyrimidines, pharmaceutical compositions containing them and their use as antibacterial

2001
- 2001-04-20 CN CNB018085962A patent/CN1249057C/zh not_active Expired - Fee Related
- 2001-04-20 KR KR1020027014451A patent/KR20020093966A/ko not_active Application Discontinuation
- 2001-04-20 ES ES01925562T patent/ES2232614T3/es not_active Expired - Lifetime
- 2001-04-20 WO PCT/EP2001/004541 patent/WO2001083476A1/en not_active Application Discontinuation
- 2001-04-20 MX MXPA02010518A patent/MXPA02010518A/es unknown
- 2001-04-20 AT AT01925562T patent/ATE284882T1/de not_active IP Right Cessation
- 2001-04-20 JP JP2001580904A patent/JP4033676B2/ja not_active Expired - Fee Related
- 2001-04-20 DE DE60107832T patent/DE60107832T2/de not_active Expired - Lifetime
- 2001-04-20 AU AU2001252269A patent/AU2001252269A1/en not_active Abandoned
- 2001-04-20 BR BR0110255-9A patent/BR0110255A/pt not_active IP Right Cessation
- 2001-04-20 US US10/258,777 patent/US6818649B2/en not_active Expired - Fee Related
- 2001-04-20 CA CA002405614A patent/CA2405614A1/en not_active Abandoned
- 2001-04-20 EP EP01925562A patent/EP1278742B1/en not_active Expired - Lifetime
2002
- 2002-10-14 ZA ZA200208271A patent/ZA200208271B/en unknown

Also Published As

Publication number	Publication date
EP1278742A1 (en)	2003-01-29
CA2405614A1 (en)	2001-11-08
BR0110255A (pt)	2003-01-07
CN1507445A (zh)	2004-06-23
KR20020093966A (ko)	2002-12-16
MXPA02010518A (es)	2003-03-10
DE60107832T2 (de)	2005-06-16
ES2232614T3 (es)	2005-06-01
ATE284882T1 (de)	2005-01-15
JP2004509839A (ja)	2004-04-02
US20030144246A1 (en)	2003-07-31
EP1278742B1 (en)	2004-12-15
CN1249057C (zh)	2006-04-05
AU2001252269A1 (en)	2001-11-12
DE60107832D1 (en)	2005-01-20
US6818649B2 (en)	2004-11-16
WO2001083476A1 (en)	2001-11-08
JP4033676B2 (ja)	2008-01-16

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KR101626627B1 (ko)	2016-06-01	아미도-티오펜 화합물 및 이의 용도
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TW201838966A (zh)	2018-11-01	取代的二氫茚－４－甲醯胺及其類似物以及其使用方法
WO2009046416A1 (en)	2009-04-09	Anilinopyrimidines as jak kinase inhibitors
WO2007126128A1 (ja)	2007-11-08	ジヒドロピラゾロピリミジノン誘導体
KR20130135826A (ko)	2013-12-11	Ａｉｄｓ를 치료하기 위한 나프트-2-일아세트산 유도체
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ZA200208271B (en)	2004-01-26	Chromenylmethyl pyrimidinediamines as antibacterial agents.
JPH10508587A (ja)	1998-08-25	ロイコトリエン生合成阻害剤としてのビスアリールカルビノールケイ皮酸
NZ766447A (en)	2021-12-24	Prc2 inhibitors
SA04250088A (ar)	2005-12-03	مركبات كيميائية
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TWI508968B (zh)	2015-11-21	用於治療呼吸道融合性病毒感染的化合物
US9126972B2 (en)	2015-09-08	2-amino-3-(imidazol-2-yl)-pyridin-4-one derivatives and their use as VEGF receptor kinase inhibitors
MXPA02004443A (es)	2002-09-02	5-bencil-2,4-diaminopirimidinas sustituidas.
AU2013326408A1 (en)	2015-04-09	Inhibitors of viral replication, their process of preparation and their therapeutical uses
WO2016204135A1 (ja)	2016-12-22	５員ヘテロ環誘導体
MXPA02010517A (es)	2003-03-10	Derivados de indol-pirimidinil-metil con actividad antibacteriana.
GB2080301A (en)	1982-02-03	Substituted Pyrimidin-2-ones, the Salts thereof, Processes for their Preparation and Pharmaceutical Compositions Containing them