DK172884B1 - Analogifremgangsmåde til fremstilling af i 5-stilling substituerede 2,4-diaminopyrimidiner og mellemprodukter til anvendels - Google Patents
Analogifremgangsmåde til fremstilling af i 5-stilling substituerede 2,4-diaminopyrimidiner og mellemprodukter til anvendels Download PDFInfo
- Publication number
- DK172884B1 DK172884B1 DK198104966A DK496681A DK172884B1 DK 172884 B1 DK172884 B1 DK 172884B1 DK 198104966 A DK198104966 A DK 198104966A DK 496681 A DK496681 A DK 496681A DK 172884 B1 DK172884 B1 DK 172884B1
- Authority
- DK
- Denmark
- Prior art keywords
- pyrimidine
- diamino
- amino
- group
- formula
- Prior art date
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- YAAWASYJIRZXSZ-UHFFFAOYSA-N pyrimidine-2,4-diamine Chemical class NC1=CC=NC(N)=N1 YAAWASYJIRZXSZ-UHFFFAOYSA-N 0.000 title claims 2
- 239000000543 intermediate Chemical class 0.000 title description 5
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 186
- -1 5-substituted 2,4-diaminopyrimidine Chemical class 0.000 claims description 109
- 229910052739 hydrogen Inorganic materials 0.000 claims description 86
- 239000001257 hydrogen Substances 0.000 claims description 85
- 238000000034 method Methods 0.000 claims description 65
- 229910052736 halogen Inorganic materials 0.000 claims description 52
- 150000002367 halogens Chemical class 0.000 claims description 51
- 150000002431 hydrogen Chemical group 0.000 claims description 43
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 39
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 35
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 32
- 125000003545 alkoxy group Chemical group 0.000 claims description 31
- 238000002360 preparation method Methods 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 20
- 125000004414 alkyl thio group Chemical group 0.000 claims description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 150000001204 N-oxides Chemical class 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 15
- 125000002252 acyl group Chemical group 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 13
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 12
- NWFFAMNYFYKTDZ-UHFFFAOYSA-N 5-[(7,8-dimethoxy-2h-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CCOC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N NWFFAMNYFYKTDZ-UHFFFAOYSA-N 0.000 claims description 11
- 125000000266 alpha-aminoacyl group Chemical group 0.000 claims description 11
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 10
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 9
- 125000001424 substituent group Chemical group 0.000 claims description 9
- MMDZZHAZMNJFMW-UHFFFAOYSA-N (2,4-diaminopyrimidin-5-yl)methanol Chemical compound NC1=NC=C(CO)C(N)=N1 MMDZZHAZMNJFMW-UHFFFAOYSA-N 0.000 claims description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 238000007327 hydrogenolysis reaction Methods 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M potassium hydroxide Inorganic materials [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical class FC(F)(F)* 0.000 claims description 6
- DDXGSHLWULMVPN-UHFFFAOYSA-N 5-[(3,4-dimethoxynaphthalen-1-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=CC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N DDXGSHLWULMVPN-UHFFFAOYSA-N 0.000 claims description 4
- YXVYIKAJJZFIQN-UHFFFAOYSA-N 5-[(7,8-dimethoxy-2-methyl-2h-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC(C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N YXVYIKAJJZFIQN-UHFFFAOYSA-N 0.000 claims description 4
- JJARGKURGQMCFR-UHFFFAOYSA-N 5-[(7-methoxyquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=CC(OC)=CC=1CC1=CN=C(N)N=C1N JJARGKURGQMCFR-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- RQRUVIVMJKJWIG-UHFFFAOYSA-N 5-[(5-amino-6-methylquinolin-8-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12N=CC=CC2=C(N)C(C)=CC=1CC1=CN=C(N)N=C1N RQRUVIVMJKJWIG-UHFFFAOYSA-N 0.000 claims description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 125000005905 mesyloxy group Chemical group 0.000 claims description 3
- 125000005184 naphthylamino group Chemical group C1(=CC=CC2=CC=CC=C12)N* 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- 230000000269 nucleophilic effect Effects 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 claims description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical class 0.000 claims description 2
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical group CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 2
- HZMAOAUHCHKWKA-UHFFFAOYSA-N 5-[(4-amino-3,6-dimethoxynaphthalen-1-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=1C(OC)=C(N)C2=CC(OC)=CC=C2C=1CC1=CN=C(N)N=C1N HZMAOAUHCHKWKA-UHFFFAOYSA-N 0.000 claims description 2
- OQFGIDFOQYUQAF-UHFFFAOYSA-N 5-[(7,8-dimethoxy-3,4-dihydro-2h-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12CCCOC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N OQFGIDFOQYUQAF-UHFFFAOYSA-N 0.000 claims description 2
- ZCONNBVJQVEVEB-UHFFFAOYSA-N 5-[(7-methoxy-8-nitroquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C([N+]([O-])=O)C(OC)=CC=1CC1=CN=C(N)N=C1N ZCONNBVJQVEVEB-UHFFFAOYSA-N 0.000 claims description 2
- LNNXDSFSUVHODF-UHFFFAOYSA-N 5-[(8-amino-7-ethoxyquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C(N)C(OCC)=CC=1CC1=CN=C(N)N=C1N LNNXDSFSUVHODF-UHFFFAOYSA-N 0.000 claims description 2
- GVNXJSKJOJYPOC-UHFFFAOYSA-N 5-[(8-amino-7-methoxyquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C(N)C(OC)=CC=1CC1=CN=C(N)N=C1N GVNXJSKJOJYPOC-UHFFFAOYSA-N 0.000 claims description 2
- HASOQHQJVLCIDS-UHFFFAOYSA-N 5-[(8-amino-7-methylquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C(N)C(C)=CC=1CC1=CN=C(N)N=C1N HASOQHQJVLCIDS-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 125000003172 aldehyde group Chemical group 0.000 claims description 2
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 150000002357 guanidines Chemical class 0.000 claims description 2
- 150000001721 carbon Chemical group 0.000 claims 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 3
- XRIXPJKXQJSYDR-UHFFFAOYSA-N 2-amino-n-[4-amino-5-[(7,8-dimethoxy-2h-chromen-5-yl)methyl]pyrimidin-2-yl]acetamide Chemical compound C=12C=CCOC2=C(OC)C(OC)=CC=1CC1=CN=C(NC(=O)CN)N=C1N XRIXPJKXQJSYDR-UHFFFAOYSA-N 0.000 claims 1
- 101150098072 20 gene Proteins 0.000 claims 1
- PWAHCQHSJOCQHQ-UHFFFAOYSA-N 4-[(2,4-diaminopyrimidin-5-yl)methyl]-2-methoxynaphthalen-1-ol Chemical compound C=12C=CC=CC2=C(O)C(OC)=CC=1CC1=CN=C(N)N=C1N PWAHCQHSJOCQHQ-UHFFFAOYSA-N 0.000 claims 1
- CSOGBPZNPVMDLW-UHFFFAOYSA-N 5-[(4-methoxynaphthalen-1-yl)methyl]pyrimidine-2,4-diamine Chemical compound C12=CC=CC=C2C(OC)=CC=C1CC1=CN=C(N)N=C1N CSOGBPZNPVMDLW-UHFFFAOYSA-N 0.000 claims 1
- URPGJMLVVSCAKX-UHFFFAOYSA-N 5-[(7,8-dimethoxy-2-methyl-4h-chromen-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12CC=C(C)OC2=C(OC)C(OC)=CC=1CC1=CN=C(N)N=C1N URPGJMLVVSCAKX-UHFFFAOYSA-N 0.000 claims 1
- GEZCGCFDXURYSM-UHFFFAOYSA-N 5-[(8-amino-7-methylsulfanylquinolin-5-yl)methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C(N)C(SC)=CC=1CC1=CN=C(N)N=C1N GEZCGCFDXURYSM-UHFFFAOYSA-N 0.000 claims 1
- ZYWHJUCYNRZOBC-UHFFFAOYSA-N 5-[[8-(dimethylamino)-7-methoxyquinolin-5-yl]methyl]pyrimidine-2,4-diamine Chemical compound C=12C=CC=NC2=C(N(C)C)C(OC)=CC=1CC1=CN=C(N)N=C1N ZYWHJUCYNRZOBC-UHFFFAOYSA-N 0.000 claims 1
- 101100173726 Arabidopsis thaliana OR23 gene Proteins 0.000 claims 1
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims 1
- 101100134927 Gallus gallus COR8 gene Proteins 0.000 claims 1
- 101150020251 NR13 gene Proteins 0.000 claims 1
- AIOWJIMWVFWROP-UHFFFAOYSA-N baquiloprim Chemical compound C12=CC=CN=C2C(N(C)C)=C(C)C=C1CC1=CN=C(N)N=C1N AIOWJIMWVFWROP-UHFFFAOYSA-N 0.000 claims 1
- 229940125773 compound 10 Drugs 0.000 claims 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 1
- 125000001145 hydrido group Chemical group *[H] 0.000 claims 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 claims 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 claims 1
- 125000005490 tosylate group Chemical class 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 202
- 238000004458 analytical method Methods 0.000 description 77
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 71
- 239000000243 solution Substances 0.000 description 70
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- 239000007787 solid Substances 0.000 description 59
- 239000000203 mixture Substances 0.000 description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 53
- 239000000047 product Substances 0.000 description 47
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
- 239000000460 chlorine Substances 0.000 description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 26
- 238000001953 recrystallisation Methods 0.000 description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 239000002244 precipitate Substances 0.000 description 19
- 238000010992 reflux Methods 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 18
- 229960005404 sulfamethoxazole Drugs 0.000 description 18
- 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 18
- 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 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 17
- 238000005481 NMR spectroscopy Methods 0.000 description 17
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 16
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 14
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- 229960001082 trimethoprim Drugs 0.000 description 14
- 239000000843 powder Substances 0.000 description 13
- ZEZQUIOIQGCIGP-UHFFFAOYSA-N 7,8-dimethoxy-2h-chromene-5-carbaldehyde Chemical compound C1=CCOC2=C(OC)C(OC)=CC(C=O)=C21 ZEZQUIOIQGCIGP-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 12
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
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- 229940125904 compound 1 Drugs 0.000 description 11
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- 239000004480 active ingredient Substances 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
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- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 9
- 229960004198 guanidine Drugs 0.000 description 9
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- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 8
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
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- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 235000019439 ethyl acetate Nutrition 0.000 description 6
- 229960000789 guanidine hydrochloride Drugs 0.000 description 6
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 6
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- DRGCXLJWMQGVJA-UHFFFAOYSA-N pyrimidine;dihydrochloride Chemical compound Cl.Cl.C1=CN=CN=C1 DRGCXLJWMQGVJA-UHFFFAOYSA-N 0.000 description 6
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 6
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
- C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/40—Nitrogen atoms attached in position 8
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/64—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with oxygen atoms directly attached in position 8
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8036135 | 1980-11-11 | ||
| GB8036135 | 1980-11-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK496681A DK496681A (da) | 1982-05-12 |
| DK172884B1 true DK172884B1 (da) | 1999-09-06 |
Family
ID=10517217
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK198104966A DK172884B1 (da) | 1980-11-11 | 1981-11-10 | Analogifremgangsmåde til fremstilling af i 5-stilling substituerede 2,4-diaminopyrimidiner og mellemprodukter til anvendels |
Country Status (35)
| Country | Link |
|---|---|
| US (4) | US4438267A (cs) |
| EP (1) | EP0051879B1 (cs) |
| JP (1) | JPS57114581A (cs) |
| KR (1) | KR880001736B1 (cs) |
| AR (1) | AR245447A1 (cs) |
| AU (1) | AU549449B2 (cs) |
| CA (1) | CA1186310A (cs) |
| CS (1) | CS273153B2 (cs) |
| CY (1) | CY1419A (cs) |
| DD (1) | DD201896A5 (cs) |
| DE (1) | DE3173752D1 (cs) |
| DK (1) | DK172884B1 (cs) |
| EG (1) | EG16107A (cs) |
| ES (5) | ES8307759A1 (cs) |
| FI (1) | FI76333C (cs) |
| GB (1) | GB2087881B (cs) |
| GR (1) | GR81317B (cs) |
| HK (1) | HK23388A (cs) |
| HU (1) | HU188762B (cs) |
| IE (1) | IE52128B1 (cs) |
| IL (1) | IL64256A (cs) |
| IT (1) | IT1210589B (cs) |
| MC (1) | MC1418A1 (cs) |
| MY (1) | MY8600678A (cs) |
| NO (2) | NO160137C (cs) |
| NZ (1) | NZ198932A (cs) |
| PH (2) | PH25053A (cs) |
| PL (4) | PL139427B1 (cs) |
| PT (1) | PT73960B (cs) |
| RU (1) | RU1819264C (cs) |
| SG (1) | SG62686G (cs) |
| SU (4) | SU1424732A3 (cs) |
| YU (5) | YU42444B (cs) |
| ZA (1) | ZA817780B (cs) |
| ZM (1) | ZM9481A1 (cs) |
Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4438267A (en) * | 1980-11-11 | 1984-03-20 | Daluge Susan M | Monoheteroring compounds and their use |
| DK190983A (da) * | 1982-05-01 | 1983-11-02 | Wellcome Found | 2,4-diamino-5-(substituerede)pyrimidiner, fremgangsmaade til deres fremstilling og mellemprodukter derfor |
| US4590271A (en) * | 1982-05-01 | 1986-05-20 | Burroughs Wellcome Co. | 2,4-diamino-5-(substituted)pyrimidines, useful as antimicrobials |
| ZA833067B (en) * | 1982-05-01 | 1984-12-24 | Wellcome Found | Antibacterial compounds |
| US4587341A (en) * | 1982-05-07 | 1986-05-06 | Burroughs Wellcome Co. | 2,4-diamino-5-(1,2,3,4-tetrahydro-(substituted or unsubstituted)-6-quinolylmethyl)pyrimidines, useful as antimicrobials |
| CA1244028A (en) * | 1983-04-14 | 1988-11-01 | Hans Maag | Pyrimidine derivatives |
| GB8603962D0 (en) * | 1986-02-18 | 1986-03-26 | Wellcome Found | Chemical compositions |
| GB8603964D0 (en) * | 1986-02-18 | 1986-03-26 | Cooper Animal Health Ltd | Compositions |
| LU86703A1 (fr) * | 1986-12-08 | 1988-07-14 | Oreal | Composition cosmetique photostable contenant un filtre uv-a et un filtre uv-b,son utilisation pour la protection de la peau contre les rayons uv et procede de stabilisation du filtre uv-a par le filtre uv-b |
| FI895821A7 (fi) * | 1988-12-07 | 1990-06-08 | The Wellcome Foundation Ltd | Farmaseuttisesti aktivisia CNS-yhdisteitä |
| GB8903978D0 (en) * | 1989-02-22 | 1989-04-05 | Coopers Animal Health | Chemical compositions |
| GB9000241D0 (en) * | 1990-01-05 | 1990-03-07 | Coopers Animal Health | Pharmaceutical use |
| RU95113597A (ru) * | 1992-12-02 | 1997-06-10 | ФМК Корпорейшн (US) | Инсектицидная композиция, способы борьбы с насекомыми |
| NO306992B1 (no) * | 1993-01-28 | 2000-01-24 | Takeda Chemical Industries Ltd | Quinolinderivater, farmasoeytiske preparater inneholdende forbindelsene og anvendelsen av forbindelsene |
| US5707996A (en) * | 1995-11-06 | 1998-01-13 | Macleod Pharmaceuticals, Inc. | Pharmaceutical solution and methods for preparation thereof |
| EP1149834A1 (en) * | 1995-12-04 | 2001-10-31 | F. Hoffmann-La Roche Ag | Diaminopyrimidines, pharmaceutical compositions containing them and their use as antibacterial |
| RU2141322C1 (ru) * | 1997-08-12 | 1999-11-20 | Голощапов Николай Михайлович | Иммуномодулятор с антимикобактериальной активностью "изофон", способ его получения и применения |
| GB0016877D0 (en) * | 2000-07-11 | 2000-08-30 | Astrazeneca Ab | Chemical compounds |
| WO2002010156A1 (en) * | 2000-07-29 | 2002-02-07 | Arpida Ag | Benzofuran derivatives and their use as antibacterial agents |
| ATE343415T1 (de) | 2001-06-29 | 2006-11-15 | Ab Science | Die verwendung von c-kit hemmer zur behandlung von entzündlichen darmerkrankungen |
| PT1401415E (pt) * | 2001-06-29 | 2006-09-29 | Ab Science | Utilizacao de derivados de n-fenil-2-pirimidino-amina para o tratamento de doencas inflamatorias |
| WO2003002106A2 (en) * | 2001-06-29 | 2003-01-09 | Ab Science | Use of tyrosine kinase inhibitions for treating allergic diseases |
| WO2003003006A2 (en) * | 2001-06-29 | 2003-01-09 | Ab Science | New potent, selective and non toxic c-kit inhibitors |
| CA2460845A1 (en) * | 2001-09-20 | 2003-03-27 | Ab Science | Use of potent, selective and non toxic c-kit inhibitors for treating interstitial cystitis |
| US20040241226A1 (en) * | 2001-09-20 | 2004-12-02 | Alain Moussy | Use of potent, selective and non-toxic c-kit inhibitors for treating bacterial infections |
| EP1461032B1 (en) * | 2001-09-20 | 2008-07-16 | AB Science | Use of c-kit inhibitors for promoting hair growth |
| BRPI0412425A (pt) * | 2003-07-11 | 2006-09-05 | Arpida Ag | compostos, intermediários, composições farmacêuticas, uso de um ou mais compostos, e, processo para a manufatura de composições farmacêuticas |
| MX2007009283A (es) * | 2005-02-18 | 2008-02-19 | Arpida Ag | Nuevos procesos para la preparacion de un benzofurano. |
| ES2601178T3 (es) * | 2005-09-01 | 2017-02-14 | F. Hoffmann-La Roche Ag | Diaminopirimidinas como moduladores de P2X3 y P3X2/3 |
| WO2010003084A2 (en) * | 2008-07-02 | 2010-01-07 | Memory Pharmaceuticals Corporation | Phosphodiesterase 4 inhibitors |
| US20120122819A1 (en) * | 2009-06-12 | 2012-05-17 | Socpra - Sciences Et Genie S.E.C. | Guanine riboswitch binding compounds and their use as antibiotics |
| CN102649786B (zh) * | 2011-02-28 | 2014-08-27 | 郑州福源动物药业有限公司 | 一种2，4-二氨基-5-(8-二甲氨基-7-甲基-5-喹啉基甲基)-2，4-(1h，3h)嘧啶的制备方法 |
| CN103755684B (zh) * | 2014-02-10 | 2015-09-09 | 青岛蔚蓝生物股份有限公司 | 一种巴喹普林的制备方法 |
| EP3981765A4 (en) * | 2019-06-06 | 2023-05-31 | Beijing Tide Pharmaceutical Co., Ltd. | P2X3 AND/OR P2X2/3 RECEPTOR ANTAGONIST, PHARMACEUTICAL COMPOSITION CONTAINING IT AND THEIR USE |
| CN110818694B (zh) * | 2019-11-18 | 2023-04-21 | 上海医药工业研究院有限公司 | 艾拉普林中间体及其应用 |
| WO2022217295A1 (en) * | 2021-04-09 | 2022-10-13 | The Trustees Of The University Of Pennsylvania | Control of protein expression with tmp-protac compounds |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3049544A (en) * | 1962-08-14 | Method for the preparation of | ||
| DE1303727B (de) | 1959-09-03 | 1976-02-05 | Ausscheidung aus: 14 45 176 The Wellcome Foundation Ltd., London | Alpha-Arylidensubstituierte Propioni-Irile |
| US3956327A (en) * | 1969-03-06 | 1976-05-11 | Burroughs Wellcome Co. | Method of preparing 2,4-diamino-5-benzyl pyrimidines |
| BE792096A (fr) * | 1971-12-01 | 1973-05-30 | Hoffmann La Roche | Nouvelles benzylpyrimidines |
| GB1468374A (en) | 1974-03-06 | 1977-03-23 | Wellcome Found | Process for preparing a pyrimidine derivative |
| US4039543A (en) | 1974-12-24 | 1977-08-02 | Hoffmann-La Roche Inc. | Benzylpyrimidines |
| GB1582245A (en) * | 1976-06-09 | 1981-01-07 | Wellcome Found | Benzyl cyanoacetal derivatives and their conversion to pyrimidine derivatives |
| DE2730467A1 (de) * | 1977-07-06 | 1979-01-18 | Basf Ag | Benzylpyrimidine, verfahren zu ihrer herstellung und diese enthaltende arzneimittel |
| US4258045A (en) * | 1979-11-30 | 1981-03-24 | Merck & Co., Inc. | Inhibitor of dihydrofolate reductase |
| US4438267A (en) * | 1980-11-11 | 1984-03-20 | Daluge Susan M | Monoheteroring compounds and their use |
-
1981
- 1981-11-09 US US06/319,644 patent/US4438267A/en not_active Expired - Lifetime
- 1981-11-10 KR KR1019810004348A patent/KR880001736B1/ko not_active Expired
- 1981-11-10 FI FI813546A patent/FI76333C/fi not_active IP Right Cessation
- 1981-11-10 DK DK198104966A patent/DK172884B1/da active Protection Beyond IP Right Term
- 1981-11-10 YU YU2663/81A patent/YU42444B/xx unknown
- 1981-11-10 IL IL64256A patent/IL64256A/xx not_active IP Right Cessation
- 1981-11-10 NO NO813804A patent/NO160137C/no not_active IP Right Cessation
- 1981-11-10 NZ NZ198932A patent/NZ198932A/en unknown
- 1981-11-10 HU HU813359A patent/HU188762B/hu unknown
- 1981-11-10 IE IE2631/81A patent/IE52128B1/en not_active IP Right Cessation
- 1981-11-10 PL PL1981239279A patent/PL139427B1/pl unknown
- 1981-11-10 CA CA000389807A patent/CA1186310A/en not_active Expired
- 1981-11-10 ES ES506969A patent/ES8307759A1/es not_active Expired
- 1981-11-10 GR GR66482A patent/GR81317B/el unknown
- 1981-11-10 PL PL1981239278A patent/PL139827B1/pl unknown
- 1981-11-10 SU SU813358051A patent/SU1424732A3/ru active
- 1981-11-10 DD DD81234745A patent/DD201896A5/de not_active IP Right Cessation
- 1981-11-10 CS CS825781A patent/CS273153B2/cs unknown
- 1981-11-10 PL PL1981233754A patent/PL139523B1/pl unknown
- 1981-11-10 PL PL1981239280A patent/PL139828B1/pl unknown
- 1981-11-10 JP JP56180271A patent/JPS57114581A/ja active Granted
- 1981-11-10 GB GB8133833A patent/GB2087881B/en not_active Expired
- 1981-11-10 MC MC811560A patent/MC1418A1/xx unknown
- 1981-11-10 IT IT8149676A patent/IT1210589B/it active
- 1981-11-10 ZA ZA817780A patent/ZA817780B/xx unknown
- 1981-11-10 PT PT73960A patent/PT73960B/pt unknown
- 1981-11-10 AU AU77334/81A patent/AU549449B2/en not_active Expired
- 1981-11-10 EG EG653/81A patent/EG16107A/xx active
- 1981-11-11 DE DE8181109631T patent/DE3173752D1/de not_active Expired
- 1981-11-11 CY CY141981A patent/CY1419A/xx unknown
- 1981-11-11 ZM ZM94/81A patent/ZM9481A1/xx unknown
- 1981-11-11 EP EP81109631A patent/EP0051879B1/en not_active Expired
-
1983
- 1983-01-27 SU SU833543245A patent/SU1318148A3/ru active
- 1983-01-31 SU SU833547444A patent/SU1306473A3/ru active
- 1983-04-02 ES ES521203A patent/ES521203A0/es active Granted
- 1983-04-02 ES ES521204A patent/ES521204A0/es active Granted
- 1983-04-02 ES ES521202A patent/ES8405378A1/es not_active Expired
- 1983-04-02 ES ES521201A patent/ES8405377A1/es not_active Expired
- 1983-09-07 PH PH29503A patent/PH25053A/en unknown
- 1983-09-07 PH PH29502A patent/PH22654A/en unknown
- 1983-10-03 YU YU01982/83A patent/YU198283A/xx unknown
- 1983-10-03 YU YU1983/83A patent/YU43551B/xx unknown
- 1983-10-03 YU YU01981/83A patent/YU198183A/xx unknown
- 1983-10-31 US US06/546,850 patent/US4587342A/en not_active Expired - Lifetime
- 1983-12-30 US US06/567,248 patent/US4603136A/en not_active Expired - Lifetime
-
1986
- 1986-02-02 RU SU863552053A patent/RU1819264C/ru active
- 1986-03-12 US US06/839,463 patent/US4761475A/en not_active Expired - Lifetime
- 1986-07-17 SG SG626/86A patent/SG62686G/en unknown
- 1986-12-30 MY MY678/86A patent/MY8600678A/xx unknown
-
1987
- 1987-01-14 SU SU874028793A patent/SU1535379A3/ru active
-
1988
- 1988-03-30 HK HK233/88A patent/HK23388A/en not_active IP Right Cessation
- 1988-06-17 AR AR88311165A patent/AR245447A1/es active
- 1988-07-26 YU YU144288A patent/YU46697B/sh unknown
-
1994
- 1994-12-29 NO NO1994029C patent/NO1994029I1/no unknown
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Legal Events
| Date | Code | Title | Description |
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| CTFF | Application for supplementary protection certificate (spc) filed |
Spc suppl protection certif: CA 2000 00006 Filing date: 20000306 Extension date: 20060927 |
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| CTFW | Supplementary protection certificate (spc) withdrawn, refused or deemed withdrawn |
Spc suppl protection certif: CA 2000 00006 Filing date: 20000306 |