CS207499B2 - Method of making the heterocyclic aminopyrimidine compounds - Google Patents
Method of making the heterocyclic aminopyrimidine compounds Download PDFInfo
- Publication number
- CS207499B2 CS207499B2 CS78959A CS95978A CS207499B2 CS 207499 B2 CS207499 B2 CS 207499B2 CS 78959 A CS78959 A CS 78959A CS 95978 A CS95978 A CS 95978A CS 207499 B2 CS207499 B2 CS 207499B2
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- CS
- Czechoslovakia
- Prior art keywords
- formula
- compound
- hydrogen
- pharmaceutically acceptable
- group
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- -1 heterocyclic aminopyrimidine compounds Chemical class 0.000 title claims description 22
- 238000004519 manufacturing process Methods 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 150000003839 salts Chemical class 0.000 claims description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 25
- 238000000034 method Methods 0.000 claims description 21
- 239000002253 acid Substances 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000002585 base Substances 0.000 claims description 8
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 238000007363 ring formation reaction Methods 0.000 claims description 7
- 150000003863 ammonium salts Chemical class 0.000 claims description 6
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 125000005359 phenoxyalkyl group Chemical group 0.000 claims description 5
- 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 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 3
- 150000001339 alkali metal compounds Chemical class 0.000 claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 150000001491 aromatic compounds Chemical class 0.000 claims description 2
- 238000009835 boiling Methods 0.000 claims description 2
- 239000012024 dehydrating agents Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 2
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 2
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 239000000047 product Substances 0.000 description 47
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 25
- 239000000203 mixture Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 21
- 238000012360 testing method Methods 0.000 description 19
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 238000004458 analytical method Methods 0.000 description 17
- 229910052757 nitrogen Inorganic materials 0.000 description 16
- 238000002844 melting Methods 0.000 description 15
- 230000008018 melting Effects 0.000 description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
- 239000007787 solid Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 238000001953 recrystallisation Methods 0.000 description 12
- 150000008064 anhydrides Chemical class 0.000 description 11
- 238000000354 decomposition reaction Methods 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000037396 body weight Effects 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 206010020751 Hypersensitivity Diseases 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 229960000583 acetic acid Drugs 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 6
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 6
- 229960003556 aminophylline Drugs 0.000 description 6
- 238000005984 hydrogenation reaction Methods 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 235000011054 acetic acid Nutrition 0.000 description 5
- 208000026935 allergic disease Diseases 0.000 description 5
- 239000000908 ammonium hydroxide Substances 0.000 description 5
- 208000006673 asthma Diseases 0.000 description 5
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
- 235000019253 formic acid Nutrition 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- YMVFJGSXZNNUDW-UHFFFAOYSA-N (4-chlorophenyl)methanamine Chemical group NCC1=CC=C(Cl)C=C1 YMVFJGSXZNNUDW-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 229910052794 bromium Inorganic materials 0.000 description 4
- 230000007883 bronchodilation Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- LSACYLWPPQLVSM-UHFFFAOYSA-N isobutyric acid anhydride Chemical compound CC(C)C(=O)OC(=O)C(C)C LSACYLWPPQLVSM-UHFFFAOYSA-N 0.000 description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000012429 reaction media Substances 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 241000700199 Cavia porcellus Species 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- 108010058846 Ovalbumin Proteins 0.000 description 3
- 206010039085 Rhinitis allergic Diseases 0.000 description 3
- 206010045240 Type I hypersensitivity Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 201000010105 allergic rhinitis Diseases 0.000 description 3
- 150000001450 anions Chemical class 0.000 description 3
- 230000003266 anti-allergic effect Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 150000001768 cations Chemical class 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000003638 chemical reducing agent Substances 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
- 230000009610 hypersensitivity Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 3
- 229960002329 methacholine Drugs 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- 210000005062 tracheal ring Anatomy 0.000 description 3
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000004262 Food Hypersensitivity Diseases 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 2
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 208000024780 Urticaria Diseases 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000003973 alkyl amines Chemical group 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 201000010435 allergic urticaria Diseases 0.000 description 2
- 230000007815 allergy Effects 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000006482 condensation reaction Methods 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 235000020932 food allergy Nutrition 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 230000022244 formylation Effects 0.000 description 2
- 238000006170 formylation reaction Methods 0.000 description 2
- 125000006277 halobenzyl group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000155 melt Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 125000003884 phenylalkyl group Chemical group 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical group [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 230000004936 stimulating effect Effects 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 229940124549 vasodilator Drugs 0.000 description 2
- 239000003071 vasodilator agent Substances 0.000 description 2
- KDDNKZCVYQDGKE-UHFFFAOYSA-N (2-chlorophenyl)methanamine Chemical compound NCC1=CC=CC=C1Cl KDDNKZCVYQDGKE-UHFFFAOYSA-N 0.000 description 1
- IIFVWLUQBAIPMJ-UHFFFAOYSA-N (4-fluorophenyl)methanamine Chemical group NCC1=CC=C(F)C=C1 IIFVWLUQBAIPMJ-UHFFFAOYSA-N 0.000 description 1
- LZIYAIRGDHSVED-UHFFFAOYSA-N 1-(bromomethyl)-3-chlorobenzene Chemical compound ClC1=CC=CC(CBr)=C1 LZIYAIRGDHSVED-UHFFFAOYSA-N 0.000 description 1
- UAWVMPOAIVZWFQ-UHFFFAOYSA-N 1-(chloromethyl)-2-methoxybenzene Chemical compound COC1=CC=CC=C1CCl UAWVMPOAIVZWFQ-UHFFFAOYSA-N 0.000 description 1
- MNDIARAMWBIKFW-UHFFFAOYSA-N 1-bromohexane Chemical compound CCCCCCBr MNDIARAMWBIKFW-UHFFFAOYSA-N 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- NNWUEBIEOFQMSS-UHFFFAOYSA-N 2-Methylpiperidine Chemical compound CC1CCCCN1 NNWUEBIEOFQMSS-UHFFFAOYSA-N 0.000 description 1
- VQUYNUJARXBNPK-UHFFFAOYSA-N 2-chloroethoxybenzene Chemical compound ClCCOC1=CC=CC=C1 VQUYNUJARXBNPK-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- YLZOPXRUQYQQID-UHFFFAOYSA-N 3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)-1-[4-[2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidin-5-yl]piperazin-1-yl]propan-1-one Chemical compound N1N=NC=2CN(CCC=21)CCC(=O)N1CCN(CC1)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F YLZOPXRUQYQQID-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- MSYFITFSZJKRQJ-UHFFFAOYSA-N 4,5-dihydroimidazol-1-amine Chemical compound NN1CCN=C1 MSYFITFSZJKRQJ-UHFFFAOYSA-N 0.000 description 1
- HRVBWEATAVUEEO-UHFFFAOYSA-N 4-(2-methylpropanoyl)-2-propan-2-yl-6,7-dihydro-1h-imidazo[1,2-a]purin-9-one Chemical compound CC(C)C(=O)N1C2=NCCN2C(=O)C2=C1NC(C(C)C)=N2 HRVBWEATAVUEEO-UHFFFAOYSA-N 0.000 description 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 1
- IJJWOSAXNHWBPR-HUBLWGQQSA-N 5-[(3as,4s,6ar)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]-n-(6-hydrazinyl-6-oxohexyl)pentanamide Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)NCCCCCC(=O)NN)SC[C@@H]21 IJJWOSAXNHWBPR-HUBLWGQQSA-N 0.000 description 1
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
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- HSPSCWZIJWKZKD-UHFFFAOYSA-N n-chloroacetamide Chemical compound CC(=O)NCl HSPSCWZIJWKZKD-UHFFFAOYSA-N 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
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- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- FWZMWMSAGOVWEZ-UHFFFAOYSA-N potassium;hydrofluoride Chemical compound F.[K] FWZMWMSAGOVWEZ-UHFFFAOYSA-N 0.000 description 1
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- 238000012545 processing Methods 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
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- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- 229940075931 sodium dithionate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- ILXAOQAXSHVHTM-UHFFFAOYSA-M sodium;2-amino-2-(hydroxymethyl)propane-1,3-diol;chloride Chemical compound [Na+].[Cl-].OCC(N)(CO)CO ILXAOQAXSHVHTM-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US76829177A | 1977-02-14 | 1977-02-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS207499B2 true CS207499B2 (en) | 1981-07-31 |
Family
ID=25082078
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS78959A CS207499B2 (en) | 1977-02-14 | 1978-02-14 | Method of making the heterocyclic aminopyrimidine compounds |
Country Status (22)
| Country | Link |
|---|---|
| JP (1) | JPS53103497A (da) |
| AR (1) | AR229078A1 (da) |
| AT (1) | AT363948B (da) |
| AU (1) | AU519271B2 (da) |
| BE (1) | BE863525A (da) |
| CS (1) | CS207499B2 (da) |
| DD (1) | DD138211A5 (da) |
| DE (1) | DE2806199A1 (da) |
| DK (1) | DK60578A (da) |
| ES (1) | ES466981A1 (da) |
| FI (1) | FI64598C (da) |
| FR (1) | FR2380282A1 (da) |
| GB (1) | GB1596320A (da) |
| GR (1) | GR72456B (da) |
| HU (1) | HU182460B (da) |
| IE (1) | IE46456B1 (da) |
| IL (1) | IL54037A (da) |
| NO (1) | NO780504L (da) |
| PH (1) | PH14777A (da) |
| SE (2) | SE7801637L (da) |
| YU (4) | YU40578A (da) |
| ZA (1) | ZA78870B (da) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| YU45690B (sh) * | 1984-12-22 | 1992-07-20 | Krka Tovarna Zdraviln.Sol.O. | Postopek za pripravo 9-(2-hidroksietoksimetil)-gvanina |
| US5270316A (en) * | 1989-10-20 | 1993-12-14 | Kyowa Hakko Kogyo Co., Ltd. | Condensed purine derivatives |
| NZ238609A (en) * | 1990-06-21 | 1993-12-23 | Schering Corp | Polycyclic guanine derivatives; preparation, pharmaceutical compositions, |
| MY125533A (en) | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
| US7772232B2 (en) | 2004-04-15 | 2010-08-10 | Bristol-Myers Squibb Company | Quinazolinyl compounds as inhibitors of potassium channel function |
| CA2656039A1 (en) | 2006-06-23 | 2007-12-27 | Incyte Corporation | Purinone derivatives as hm74a agonists |
-
1978
- 1978-01-31 BE BE184799A patent/BE863525A/xx not_active IP Right Cessation
- 1978-02-08 GR GR55383A patent/GR72456B/el unknown
- 1978-02-09 FI FI780427A patent/FI64598C/fi not_active IP Right Cessation
- 1978-02-10 DK DK60578A patent/DK60578A/da not_active Application Discontinuation
- 1978-02-13 DD DD78203684A patent/DD138211A5/xx unknown
- 1978-02-13 HU HU78BI561A patent/HU182460B/hu unknown
- 1978-02-13 SE SE7801637A patent/SE7801637L/xx unknown
- 1978-02-13 AU AU33221/78A patent/AU519271B2/en not_active Expired
- 1978-02-13 IL IL54037A patent/IL54037A/xx unknown
- 1978-02-13 GB GB5629/78A patent/GB1596320A/en not_active Expired
- 1978-02-13 AR AR271079A patent/AR229078A1/es active
- 1978-02-13 IE IE310/78A patent/IE46456B1/en unknown
- 1978-02-14 DE DE19782806199 patent/DE2806199A1/de not_active Withdrawn
- 1978-02-14 CS CS78959A patent/CS207499B2/cs unknown
- 1978-02-14 ZA ZA00780870A patent/ZA78870B/xx unknown
- 1978-02-14 ES ES466981A patent/ES466981A1/es not_active Expired
- 1978-02-14 NO NO780504A patent/NO780504L/no unknown
- 1978-02-14 FR FR7804165A patent/FR2380282A1/fr active Granted
- 1978-02-14 JP JP1505778A patent/JPS53103497A/ja active Pending
- 1978-02-14 AT AT0106778A patent/AT363948B/de not_active IP Right Cessation
- 1978-02-15 PH PH20777A patent/PH14777A/en unknown
- 1978-02-22 YU YU00405/78A patent/YU40578A/xx unknown
-
1982
- 1982-09-02 YU YU01986/82A patent/YU198682A/xx unknown
- 1982-09-02 YU YU01988/82A patent/YU198882A/xx unknown
- 1982-09-02 YU YU01987/82A patent/YU198782A/xx unknown
-
1983
- 1983-03-15 SE SE8301408A patent/SE8301408L/sv not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| SE7801637L (sv) | 1978-08-15 |
| SE8301408D0 (sv) | 1983-03-15 |
| NO780504L (no) | 1978-08-15 |
| DE2806199A1 (de) | 1978-08-17 |
| IE780310L (en) | 1978-08-14 |
| FR2380282A1 (fr) | 1978-09-08 |
| BE863525A (fr) | 1978-07-31 |
| AR229078A1 (es) | 1983-06-15 |
| YU198682A (en) | 1983-04-30 |
| ATA106778A (de) | 1981-02-15 |
| FR2380282B1 (da) | 1982-03-05 |
| FI780427A7 (fi) | 1978-08-15 |
| IE46456B1 (en) | 1983-06-15 |
| FI64598C (fi) | 1983-12-12 |
| DK60578A (da) | 1978-08-15 |
| ES466981A1 (es) | 1979-08-16 |
| DD138211A5 (de) | 1979-10-17 |
| GR72456B (da) | 1983-11-09 |
| YU198782A (en) | 1983-04-30 |
| SE8301408L (sv) | 1983-03-15 |
| AU3322178A (en) | 1979-08-23 |
| YU40578A (en) | 1983-04-30 |
| IL54037A0 (en) | 1978-04-30 |
| HU182460B (en) | 1984-01-30 |
| YU198882A (en) | 1983-04-30 |
| AT363948B (de) | 1981-09-10 |
| JPS53103497A (en) | 1978-09-08 |
| PH14777A (en) | 1981-12-09 |
| ZA78870B (en) | 1979-01-31 |
| AU519271B2 (en) | 1981-11-19 |
| IL54037A (en) | 1982-02-28 |
| GB1596320A (en) | 1981-08-26 |
| FI64598B (fi) | 1983-08-31 |
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