NO813326L - Analogifremgangsmaate for fremstilling av farmasoeytisk aktive pyrimidonderivater. - Google Patents
Analogifremgangsmaate for fremstilling av farmasoeytisk aktive pyrimidonderivater.Info
- Publication number
- NO813326L NO813326L NO813326A NO813326A NO813326L NO 813326 L NO813326 L NO 813326L NO 813326 A NO813326 A NO 813326A NO 813326 A NO813326 A NO 813326A NO 813326 L NO813326 L NO 813326L
- Authority
- NO
- Norway
- Prior art keywords
- pyridyl
- formula
- dimethylaminomethyl
- group
- pyrimidone
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 14
- 238000002360 preparation method Methods 0.000 title claims description 12
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical class OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 title claims description 5
- 150000001875 compounds Chemical class 0.000 claims description 59
- -1 nitroamino Chemical group 0.000 claims description 51
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 20
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- FLDCYXOIVORVJI-UHFFFAOYSA-N 2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethanamine Chemical compound CN(C)CC1=CC=NC(CSCCN)=C1 FLDCYXOIVORVJI-UHFFFAOYSA-N 0.000 claims description 10
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Chemical group 0.000 claims description 6
- 239000011593 sulfur Chemical group 0.000 claims description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 150000003573 thiols Chemical class 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- GXOLLTTXFMGTHF-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-5-[(6-methylpyridin-3-yl)methyl]-1h-pyrimidin-6-one Chemical compound CN(C)CC1=CC=NC(CSCCNC=2NC(=O)C(CC=3C=NC(C)=CC=3)=CN=2)=C1 GXOLLTTXFMGTHF-UHFFFAOYSA-N 0.000 claims description 4
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 4
- 239000005864 Sulphur Substances 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- KWBSLRQDOHBJPQ-UHFFFAOYSA-N n-[5-[(6-methylpyridin-3-yl)methyl]-6-oxo-1h-pyrimidin-2-yl]nitramide Chemical compound C1=NC(C)=CC=C1CC1=CN=C(N[N+]([O-])=O)NC1=O KWBSLRQDOHBJPQ-UHFFFAOYSA-N 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])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
- 229910052760 oxygen Chemical group 0.000 claims description 3
- 239000001301 oxygen Chemical group 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- UQGQVSVQNBXMBA-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-5-[(5,6-dimethylpyridin-3-yl)methyl]-1h-pyrimidin-6-one Chemical compound CN(C)CC1=CC=NC(CSCCNC=2NC(=O)C(CC=3C=C(C)C(C)=NC=3)=CN=2)=C1 UQGQVSVQNBXMBA-UHFFFAOYSA-N 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 2
- 125000004633 N-oxo-pyridyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- IIQFIDKGTDXLBU-UHFFFAOYSA-N benzyl thiohypochlorite Chemical compound ClSCC1=CC=CC=C1 IIQFIDKGTDXLBU-UHFFFAOYSA-N 0.000 claims description 2
- UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 claims description 2
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002541 furyl group Chemical group 0.000 claims description 2
- 229960003151 mercaptamine Drugs 0.000 claims description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- WCCXSTMOFAXKAF-UHFFFAOYSA-N n-[5-[(5,6-dimethylpyridin-3-yl)methyl]-6-oxo-1h-pyrimidin-2-yl]nitramide Chemical compound N1=C(C)C(C)=CC(CC=2C(NC(N[N+]([O-])=O)=NC=2)=O)=C1 WCCXSTMOFAXKAF-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 150000003141 primary amines Chemical class 0.000 claims description 2
- 125000005493 quinolyl group Chemical group 0.000 claims description 2
- 125000000335 thiazolyl group Chemical group 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000002431 hydrogen Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 74
- 229960001340 histamine Drugs 0.000 description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- 239000000243 solution Substances 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000000203 mixture Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 210000002784 stomach Anatomy 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000005557 antagonist Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 230000009858 acid secretion Effects 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 230000001404 mediated effect Effects 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 6
- 230000027119 gastric acid secretion Effects 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000012280 lithium aluminium hydride Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 239000000825 pharmaceutical preparation Substances 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000003485 histamine H2 receptor antagonist Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- QTSXDKLFNSWKJW-UHFFFAOYSA-N [4-[(dimethylamino)methyl]pyridin-2-yl]methanol Chemical compound CN(C)CC1=CC=NC(CO)=C1 QTSXDKLFNSWKJW-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000002026 chloroform extract Substances 0.000 description 3
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 3
- 229960001380 cimetidine Drugs 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
- 210000003238 esophagus Anatomy 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 210000004731 jugular vein Anatomy 0.000 description 3
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 3
- 229960000582 mepyramine Drugs 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- 150000008081 1H-pyrimidin-4-ones Chemical class 0.000 description 2
- MMVBJOBTOMJNHE-UHFFFAOYSA-N 2-(hydroxymethyl)pyridine-4-carbonitrile Chemical compound OCC1=CC(C#N)=CC=N1 MMVBJOBTOMJNHE-UHFFFAOYSA-N 0.000 description 2
- UAMMZRRNHWAZQN-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethyl]guanidine Chemical compound CN(C)CC1=CC=NC(CSCCNC(N)=N)=C1 UAMMZRRNHWAZQN-UHFFFAOYSA-N 0.000 description 2
- WCBHOPYXRZWSBD-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-5-[(2-methoxypyridin-4-yl)methyl]-1h-pyrimidin-6-one Chemical compound C1=NC(OC)=CC(CC=2C(NC(NCCSCC=3N=CC=C(CN(C)C)C=3)=NC=2)=O)=C1 WCBHOPYXRZWSBD-UHFFFAOYSA-N 0.000 description 2
- MQKAYUJTJYIUFY-UHFFFAOYSA-N 2-[4-[4-[(dimethylamino)methyl]pyridin-2-yl]butylamino]-5-[(6-methylpyridin-3-yl)methyl]-1h-pyrimidin-6-one Chemical compound CN(C)CC1=CC=NC(CCCCNC=2NC(=O)C(CC=3C=NC(C)=CC=3)=CN=2)=C1 MQKAYUJTJYIUFY-UHFFFAOYSA-N 0.000 description 2
- NCAYOFNHOSOVPO-UHFFFAOYSA-N 4-[4-[(dimethylamino)methyl]pyridin-2-yl]butan-1-amine Chemical compound CN(C)CC1=CC=NC(CCCCN)=C1 NCAYOFNHOSOVPO-UHFFFAOYSA-N 0.000 description 2
- LDPCTALKCRAISR-UHFFFAOYSA-N 4-[4-[(dimethylamino)methyl]pyridin-2-yl]butanenitrile Chemical compound CN(C)CC1=CC=NC(CCCC#N)=C1 LDPCTALKCRAISR-UHFFFAOYSA-N 0.000 description 2
- YXBVMSQDRLXPQV-UHFFFAOYSA-N 4-cyanobutanoic acid Chemical compound OC(=O)CCCC#N YXBVMSQDRLXPQV-UHFFFAOYSA-N 0.000 description 2
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 102000000543 Histamine Receptors Human genes 0.000 description 2
- 108010002059 Histamine Receptors Proteins 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 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 2
- 206010061218 Inflammation Diseases 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 210000003815 abdominal wall Anatomy 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 230000020335 dealkylation Effects 0.000 description 2
- 238000006900 dealkylation reaction Methods 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000004927 fusion Effects 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 210000002837 heart atrium Anatomy 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 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
- SDDKIZNHOCEXTF-UHFFFAOYSA-N methyl carbamimidothioate Chemical compound CSC(N)=N SDDKIZNHOCEXTF-UHFFFAOYSA-N 0.000 description 2
- VJOFNWDVXXUHAG-UHFFFAOYSA-N n,n-dimethyl-1-pyridin-4-ylmethanamine Chemical compound CN(C)CC1=CC=NC=C1 VJOFNWDVXXUHAG-UHFFFAOYSA-N 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 229910001961 silver nitrate Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- BZZXQZOBAUXLHZ-UHFFFAOYSA-N (c-methylsulfanylcarbonimidoyl)azanium;sulfate Chemical compound CSC(N)=N.CSC(N)=N.OS(O)(=O)=O BZZXQZOBAUXLHZ-UHFFFAOYSA-N 0.000 description 1
- DRTQHJPVMGBUCF-UCVXFZOQSA-N 1-[(2s,3s,4s,5s)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidine-2,4-dione Chemical compound O[C@H]1[C@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UCVXFZOQSA-N 0.000 description 1
- VLYANRUKOFGNRQ-UHFFFAOYSA-N 1-[2-(chloromethyl)pyridin-4-yl]-n,n-dimethylmethanamine;dihydrochloride Chemical compound Cl.Cl.CN(C)CC1=CC=NC(CCl)=C1 VLYANRUKOFGNRQ-UHFFFAOYSA-N 0.000 description 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 description 1
- MRMSTGSIEIVFJC-UHFFFAOYSA-N 2-(3-aminopropoxy)-n,n-diethylpyridine-4-carboxamide Chemical compound CCN(CC)C(=O)C1=CC=NC(OCCCN)=C1 MRMSTGSIEIVFJC-UHFFFAOYSA-N 0.000 description 1
- QGVZSUCHKXXZPM-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-5-(pyridin-2-ylmethyl)-1h-pyrimidin-6-one Chemical compound CN(C)CC1=CC=NC(CSCCNC=2NC(=O)C(CC=3N=CC=CC=3)=CN=2)=C1 QGVZSUCHKXXZPM-UHFFFAOYSA-N 0.000 description 1
- LNDPBTJQBFSBPF-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one Chemical compound CN(C)CC1=CC=NC(CSCCNC=2NC(=O)C(CC=3C=NC=CC=3)=CN=2)=C1 LNDPBTJQBFSBPF-UHFFFAOYSA-N 0.000 description 1
- MSIYBFGLSXMTBR-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-5-(pyridin-4-ylmethyl)-1h-pyrimidin-6-one Chemical compound CN(C)CC1=CC=NC(CSCCNC=2NC(=O)C(CC=3C=CN=CC=3)=CN=2)=C1 MSIYBFGLSXMTBR-UHFFFAOYSA-N 0.000 description 1
- HXMCTZWYEMFQKI-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-5-[(2-oxo-1h-pyridin-4-yl)methyl]-1h-pyrimidin-6-one;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.CN(C)CC1=CC=NC(CSCCNC=2NC(=O)C(CC=3C=C(O)N=CC=3)=CN=2)=C1 HXMCTZWYEMFQKI-UHFFFAOYSA-N 0.000 description 1
- GLOZDBZEFZHSMN-UHFFFAOYSA-N 2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-5-[[5-[(dimethylamino)methyl]thiophen-2-yl]methyl]-1h-pyrimidin-6-one Chemical compound S1C(CN(C)C)=CC=C1CC(C(N1)=O)=CN=C1NCCSCC1=CC(CN(C)C)=CC=N1 GLOZDBZEFZHSMN-UHFFFAOYSA-N 0.000 description 1
- CQHNRTARJDLTFB-UHFFFAOYSA-N 2-[3-[4-(diethylaminomethyl)pyridin-2-yl]oxypropylamino]-5-[(6-methylpyridin-3-yl)methyl]-1h-pyrimidin-6-one Chemical compound CCN(CC)CC1=CC=NC(OCCCNC=2NC(=O)C(CC=3C=NC(C)=CC=3)=CN=2)=C1 CQHNRTARJDLTFB-UHFFFAOYSA-N 0.000 description 1
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
- GETJGKPZMMAFNU-UHFFFAOYSA-N 2-chloro-n,n-diethylpyridine-4-carboxamide Chemical compound CCN(CC)C(=O)C1=CC=NC(Cl)=C1 GETJGKPZMMAFNU-UHFFFAOYSA-N 0.000 description 1
- DADQIFJRAOADQS-UHFFFAOYSA-N 2-methylsulfanyl-5-(pyridin-2-ylmethyl)-1h-pyrimidin-6-one Chemical compound O=C1NC(SC)=NC=C1CC1=CC=CC=N1 DADQIFJRAOADQS-UHFFFAOYSA-N 0.000 description 1
- KZRZMQRVMQVELJ-UHFFFAOYSA-N 2-methylsulfanyl-5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one Chemical compound O=C1NC(SC)=NC=C1CC1=CC=CN=C1 KZRZMQRVMQVELJ-UHFFFAOYSA-N 0.000 description 1
- CDXLMOHXDMHKOQ-UHFFFAOYSA-N 2-methylsulfanyl-5-(pyridin-4-ylmethyl)-1h-pyrimidin-6-one Chemical compound O=C1NC(SC)=NC=C1CC1=CC=NC=C1 CDXLMOHXDMHKOQ-UHFFFAOYSA-N 0.000 description 1
- UYHSQVMHSFXUOA-UHFFFAOYSA-N 2-methylthiouracil Chemical compound CSC1=NC=CC(O)=N1 UYHSQVMHSFXUOA-UHFFFAOYSA-N 0.000 description 1
- SULMWAWLJZWIIS-UHFFFAOYSA-N 3-[4-(diethylaminomethyl)pyridin-2-yl]oxypropan-1-amine Chemical compound CCN(CC)CC1=CC=NC(OCCCN)=C1 SULMWAWLJZWIIS-UHFFFAOYSA-N 0.000 description 1
- KLTIYOMUGIPJNM-UHFFFAOYSA-N 5-(pyridin-3-ylmethyl)-1h-pyrimidin-6-one Chemical compound O=C1NC=NC=C1CC1=CC=CN=C1 KLTIYOMUGIPJNM-UHFFFAOYSA-N 0.000 description 1
- HHUUZVMDVRFBPS-UHFFFAOYSA-N 5-(pyridin-3-ylmethyl)-2-[2-(pyridin-2-ylmethylsulfanyl)ethylamino]-1h-pyrimidin-6-one Chemical compound N=1C=C(CC=2C=NC=CC=2)C(=O)NC=1NCCSCC1=CC=CC=N1 HHUUZVMDVRFBPS-UHFFFAOYSA-N 0.000 description 1
- MDHJHMABPLBOIM-UHFFFAOYSA-N 5-[(2-oxo-1H-pyridin-4-yl)methyl]-1H-pyrimidin-6-one Chemical compound OC1=NC=CC(=C1)CC=1C(NC=NC=1)=O MDHJHMABPLBOIM-UHFFFAOYSA-N 0.000 description 1
- ZAHFCGSUQXZCAI-UHFFFAOYSA-N 5-[[6-[(dimethylamino)methyl]pyridin-3-yl]methyl]-2-[2-[[4-[(dimethylamino)methyl]pyridin-2-yl]methylsulfanyl]ethylamino]-1h-pyrimidin-6-one Chemical compound CN(C)CC1=CC=NC(CSCCNC=2NC(=O)C(CC=3C=NC(CN(C)C)=CC=3)=CN=2)=C1 ZAHFCGSUQXZCAI-UHFFFAOYSA-N 0.000 description 1
- TVPRITKRWWSQFW-UHFFFAOYSA-N 5-methyl-2-methylsulfanyl-1h-pyrimidin-6-one Chemical compound CSC1=NC=C(C)C(=O)N1 TVPRITKRWWSQFW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 239000004160 Ammonium persulphate Substances 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- AAXATIIFBYBMPG-UHFFFAOYSA-N CN(C)CC1=CC=NC(CSCCNC=2OC=C(CC=3C=C(C)C(C)=NC=3)C(=N)C=2)=C1 Chemical compound CN(C)CC1=CC=NC(CSCCNC=2OC=C(CC=3C=C(C)C(C)=NC=3)C(=N)C=2)=C1 AAXATIIFBYBMPG-UHFFFAOYSA-N 0.000 description 1
- 241001631457 Cannula Species 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 1
- 201000004624 Dermatitis Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- 102100021022 Gastrin Human genes 0.000 description 1
- 108010052343 Gastrins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 102000003710 Histamine H2 Receptors Human genes 0.000 description 1
- 108090000050 Histamine H2 Receptors Proteins 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 206010046274 Upper gastrointestinal haemorrhage Diseases 0.000 description 1
- 206010047139 Vasoconstriction Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- ZGBKTQQZUZJZKC-UHFFFAOYSA-N [4-(aminomethyl)pyridin-2-yl]methanol Chemical compound NCC1=CC=NC(CO)=C1 ZGBKTQQZUZJZKC-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000005273 aeration Methods 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000019395 ammonium persulphate Nutrition 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- RIMGDBZXWSGBQN-UHFFFAOYSA-N burimamide Chemical compound CNC(=S)NCCCCC1=CN=C[N]1 RIMGDBZXWSGBQN-UHFFFAOYSA-N 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940097265 cysteamine hydrochloride Drugs 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000002183 duodenal effect Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- UVNKOIZLWHTKPM-UHFFFAOYSA-N ethyl 2-formyl-4-(6-methylpyridin-3-yl)butanoate Chemical compound CCOC(=O)C(C=O)CCC1=CC=C(C)N=C1 UVNKOIZLWHTKPM-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000005469 granulation Methods 0.000 description 1
- 230000003179 granulation Effects 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 150000002357 guanidines Chemical class 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 238000007031 hydroxymethylation reaction Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- SFSUXRAHQUOTQK-UHFFFAOYSA-N n-[5-[[4-[(dimethylamino)methyl]phenyl]methyl]-6-oxo-1h-pyrimidin-2-yl]nitramide Chemical compound C1=CC(CN(C)C)=CC=C1CC1=CN=C(N[N+]([O-])=O)NC1=O SFSUXRAHQUOTQK-UHFFFAOYSA-N 0.000 description 1
- FAAWMIBKLHPTMX-UHFFFAOYSA-N n-[5-[[5-[(dimethylamino)methyl]furan-2-yl]methyl]-6-oxo-1h-pyrimidin-2-yl]nitramide Chemical compound O1C(CN(C)C)=CC=C1CC1=CN=C(N[N+]([O-])=O)NC1=O FAAWMIBKLHPTMX-UHFFFAOYSA-N 0.000 description 1
- FGABFOAOTROIDF-UHFFFAOYSA-N n-[5-[[6-[(dimethylamino)methyl]pyridin-3-yl]methyl]-6-oxo-1h-pyrimidin-2-yl]nitramide Chemical compound C1=NC(CN(C)C)=CC=C1CC1=CN=C(N[N+]([O-])=O)NC1=O FGABFOAOTROIDF-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960004838 phosphoric acid Drugs 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 description 1
- 150000008318 pyrimidones Chemical class 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 210000005245 right atrium Anatomy 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 210000004767 rumen Anatomy 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 238000013223 sprague-dawley female rat Methods 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940032330 sulfuric acid Drugs 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 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
- RIOQSEWOXXDEQQ-UHFFFAOYSA-O triphenylphosphanium Chemical compound C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-O 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/38—Radicals substituted by singly-bound nitrogen atoms having only hydrogen or hydrocarbon radicals attached to the substituent nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Steroid Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8031685 | 1980-10-01 |
Publications (1)
Publication Number | Publication Date |
---|---|
NO813326L true NO813326L (no) | 1982-04-02 |
Family
ID=10516418
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO813326A NO813326L (no) | 1980-10-01 | 1981-09-30 | Analogifremgangsmaate for fremstilling av farmasoeytisk aktive pyrimidonderivater. |
Country Status (22)
Country | Link |
---|---|
US (1) | US4385058A (fr) |
EP (1) | EP0049173B1 (fr) |
JP (1) | JPS5791986A (fr) |
KR (1) | KR830007630A (fr) |
AT (1) | ATA420581A (fr) |
AU (1) | AU547215B2 (fr) |
CA (1) | CA1170261A (fr) |
DD (1) | DD200469A5 (fr) |
DE (1) | DE3171234D1 (fr) |
DK (1) | DK435681A (fr) |
ES (1) | ES8301966A1 (fr) |
FI (1) | FI813054L (fr) |
GR (1) | GR75783B (fr) |
IL (1) | IL63913A0 (fr) |
NO (1) | NO813326L (fr) |
PH (2) | PH17948A (fr) |
PL (1) | PL233256A1 (fr) |
PT (1) | PT73691B (fr) |
RO (1) | RO82214A (fr) |
YU (1) | YU236881A (fr) |
ZA (1) | ZA816794B (fr) |
ZW (1) | ZW21281A1 (fr) |
Families Citing this family (23)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
ZA823149B (en) * | 1981-05-27 | 1983-03-30 | Smithkline Beckman Corp | Chemical process |
PT74865B (en) * | 1981-05-27 | 1983-12-07 | Smithkline Beckman Corp | Process of preparing a 2-(pyridylbutylamino)-pyrimidone and of its pharmaceutically acceptable salts |
US4808589A (en) * | 1982-02-20 | 1989-02-28 | Smith Kline & French Laboratories Limited | Pyrimidone derivatives |
EP0089153B1 (fr) * | 1982-03-17 | 1986-09-24 | Smith Kline & French Laboratories Limited | Dérivés de pyridine |
DE3365869D1 (en) * | 1982-07-30 | 1986-10-09 | Smith Kline French Lab | Amino pyrimidinones and their preparation |
PT77287B (en) * | 1982-10-01 | 1986-02-04 | Smith Kline French Lab | Compound |
AU1956283A (en) * | 1982-10-02 | 1984-04-05 | Smith Kline & French Laboratories Limited | 1-(3-(4-(substited aminomethyl)pyrid-2-yl-oxy)-prop-1-yl- amino) - 2-aminocyclobut-i-ene-3,4-diones |
PT77623B (en) * | 1982-11-25 | 1986-03-19 | Smith Kline French Lab | Process for the preparation of a small class of histamine h2-antagonists |
JO1274B1 (en) * | 1982-12-03 | 1985-04-20 | سيدني ساخ جورج | Pyridine derivatives |
DE3374313D1 (de) * | 1982-12-23 | 1987-12-10 | Smith Kline French Lab | Aminopyrimidinone derivatives as histamine h1-antagonists |
DK584683A (da) * | 1982-12-23 | 1984-06-24 | Smith Kline French Lab | Pyridinderivater |
GB8311443D0 (en) * | 1983-04-27 | 1983-06-02 | Smith Kline French Lab | Chemical compounds |
GB8318638D0 (en) * | 1983-07-09 | 1983-08-10 | Smith Kline French Lab | Chemical compounds |
GB8319874D0 (en) * | 1983-07-23 | 1983-08-24 | Smith Kline French Lab | Compounds |
GB8320505D0 (en) * | 1983-07-29 | 1983-09-01 | Smith Kline French Lab | Chemical compounds |
US4772704A (en) * | 1983-09-21 | 1988-09-20 | Bristol-Myers Company | 2,5-disubstituted-4(3H)-pyrimidones having histamine H2 -receptor antagonist activity |
GB8332091D0 (en) * | 1983-12-01 | 1984-01-11 | Smith Kline French Lab | Chemical compounds |
GB8421427D0 (en) * | 1984-08-23 | 1984-09-26 | Smith Kline French Lab | Chemical compounds |
CA1275097A (fr) * | 1984-10-02 | 1990-10-09 | Fujio Nohara | Derives de pyridyloxy |
GB8601816D0 (en) * | 1986-01-25 | 1986-02-26 | Smith Kline French Lab | Pyridine derivatives |
US4931452A (en) * | 1987-11-10 | 1990-06-05 | The Dow Chemical Company | N-cyanomethyl-2-pyridinone insecticides |
JP2807577B2 (ja) * | 1990-06-15 | 1998-10-08 | エーザイ株式会社 | 環状アミド誘導体 |
WO2022034121A1 (fr) | 2020-08-11 | 2022-02-17 | Université De Strasbourg | Bloqueurs de h2 ciblant des macrophages du foie pour la prévention et le traitement d'une maladie du foie et du cancer |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1419994A (en) * | 1973-05-03 | 1976-01-07 | Smith Kline French Lab | Heterocyclicalkylaminotheterocyclic compounds methods for their preparation and compositions comprising them |
US4218452A (en) * | 1975-10-02 | 1980-08-19 | Smith Kline & French Laboratories Limited | Substituted 4-pyrimidone compounds, compositions and methods of use |
US4145546A (en) * | 1975-10-02 | 1979-03-20 | Smith Kline & French Laboratories Limited | 4-Pyrimidone compounds |
IN146736B (fr) * | 1975-10-02 | 1979-08-25 | Smith Kline French Lab | |
US4154834A (en) * | 1975-12-29 | 1979-05-15 | Smith Kline & French Laboratories Limited | Substituted isocytosines having histamine H2 -antagonist activity |
MW5076A1 (en) * | 1975-12-29 | 1978-02-08 | Smith Kline French Lab | Pharmacologicalle active compounds |
IN151188B (fr) * | 1978-02-13 | 1983-03-05 | Smith Kline French Lab | |
US4227000A (en) * | 1978-04-11 | 1980-10-07 | Smith Kline & French Laboratories Limited | Intermediates in the process for making histamine antagonists |
IL57416A (en) * | 1978-05-30 | 1983-03-31 | Smith Kline French Lab | Nitro compounds,processes for preparing them and compositions containing them |
ZA793443B (en) * | 1978-07-26 | 1980-12-31 | Glaxo Group Ltd | Heterocyclic derivatives |
US4250316A (en) * | 1978-11-24 | 1981-02-10 | Bristol-Myers Company | Pyridyl guanidine anti-ulcer agents |
US4255428A (en) * | 1979-03-24 | 1981-03-10 | Smith Kline & French Laboratories Limited | 5-(Hydroxypyridylalkyl)-4-pyrimidones |
CA1140129A (fr) * | 1979-08-21 | 1983-01-25 | Ronald J. King | Derives de la 4-pyrimidone |
-
1981
- 1981-08-28 ZW ZW212/81A patent/ZW21281A1/xx unknown
- 1981-09-16 US US06/302,941 patent/US4385058A/en not_active Expired - Fee Related
- 1981-09-17 PT PT73691A patent/PT73691B/pt unknown
- 1981-09-22 IL IL63913A patent/IL63913A0/xx unknown
- 1981-09-26 RO RO81105409A patent/RO82214A/fr unknown
- 1981-09-30 JP JP56156896A patent/JPS5791986A/ja active Granted
- 1981-09-30 NO NO813326A patent/NO813326L/no unknown
- 1981-09-30 KR KR1019810003735A patent/KR830007630A/ko unknown
- 1981-09-30 PH PH26291A patent/PH17948A/en unknown
- 1981-09-30 GR GR66162A patent/GR75783B/el unknown
- 1981-09-30 ES ES505898A patent/ES8301966A1/es not_active Expired
- 1981-09-30 PH PH26291A patent/PH17950A/en unknown
- 1981-09-30 CA CA000386988A patent/CA1170261A/fr not_active Expired
- 1981-09-30 PL PL23325681A patent/PL233256A1/xx unknown
- 1981-10-01 ZA ZA816794A patent/ZA816794B/xx unknown
- 1981-10-01 EP EP81304540A patent/EP0049173B1/fr not_active Expired
- 1981-10-01 AU AU75951/81A patent/AU547215B2/en not_active Ceased
- 1981-10-01 AT AT0420581A patent/ATA420581A/de not_active Application Discontinuation
- 1981-10-01 DE DE8181304540T patent/DE3171234D1/de not_active Expired
- 1981-10-01 DK DK435681A patent/DK435681A/da not_active Application Discontinuation
- 1981-10-01 FI FI810354A patent/FI813054L/fi not_active Application Discontinuation
- 1981-10-01 DD DD81233796A patent/DD200469A5/de unknown
- 1981-10-01 YU YU02368/81A patent/YU236881A/xx unknown
Also Published As
Publication number | Publication date |
---|---|
RO82214A (fr) | 1983-07-07 |
JPS6328069B2 (fr) | 1988-06-07 |
KR830007630A (ko) | 1983-11-04 |
RO82214B (ro) | 1983-06-30 |
ES505898A0 (es) | 1983-01-01 |
EP0049173B1 (fr) | 1985-07-03 |
ZW21281A1 (en) | 1981-11-18 |
PH17950A (en) | 1985-02-11 |
ES8301966A1 (es) | 1983-01-01 |
US4385058A (en) | 1983-05-24 |
AU7595181A (en) | 1982-04-08 |
AU547215B2 (en) | 1985-10-10 |
PH17948A (en) | 1985-02-11 |
ATA420581A (de) | 1985-03-15 |
PT73691A (en) | 1981-10-01 |
DD200469A5 (de) | 1983-05-04 |
IL63913A0 (en) | 1981-12-31 |
GR75783B (fr) | 1984-08-02 |
EP0049173A2 (fr) | 1982-04-07 |
EP0049173A3 (en) | 1982-06-30 |
DK435681A (da) | 1982-04-02 |
ZA816794B (en) | 1982-10-27 |
JPS5791986A (en) | 1982-06-08 |
YU236881A (en) | 1984-02-29 |
PL233256A1 (fr) | 1982-11-08 |
CA1170261A (fr) | 1984-07-03 |
DE3171234D1 (en) | 1985-08-08 |
FI813054L (fi) | 1982-04-02 |
PT73691B (en) | 1982-12-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO813326L (no) | Analogifremgangsmaate for fremstilling av farmasoeytisk aktive pyrimidonderivater. | |
FI66000B (fi) | Foerfarande foer framstaellning av terapeutiskt aktiva 2-amino-4-pyrimidonderivat | |
US3876647A (en) | Certain n-cyanoguanidines | |
FI66849B (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara 2(h)-pyridinonderivat | |
DE2658267A1 (de) | Pyrimid-4-on- und -thion-derivate, ihre salze mit saeuren, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
US4444772A (en) | Histamine H1 -antagonists | |
US4521418A (en) | Guanidinothiazolyl derivatives | |
US4758576A (en) | Pyridine derivatives and use as histamine H2 antagonists | |
EP0286979A1 (fr) | Dérivés substitués d'anilide | |
US4388317A (en) | Pyrimidones having histamine H2 -antagonist activity | |
US4639519A (en) | 2-substituted alkylaminopyrimidones useful as H2 -antagonists and antiinflamatory agents | |
US4439609A (en) | Pyridines | |
US4607107A (en) | (4-aminoalkyl-2-pyridyl alkyl)guanidines | |
US4447611A (en) | Benzo-fused and heterocyclic fused imidazole anti-ulcer agents | |
US4894372A (en) | Pyridine compounds which have useful histamine-H2 antagonist activity | |
EP0028117B1 (fr) | Dérivés de guanidine, procédé pour leur préparation et compositions les contenant | |
US4359466A (en) | Guanidine compounds | |
JPS58170757A (ja) | ピリジン誘導体 | |
US4443456A (en) | Pyridyl alkylene amidinoureas | |
GB1582527A (en) | Pyrimidone and thiopyrimidone derivatives | |
KR830000313B1 (ko) | 피리미돈의 제조방법 | |
PL123693B1 (en) | Process for preparing novel derivatives of pyrimidone | |
GB2101599A (en) | Derivatives of 4-pyrimidone | |
DE3116791A1 (de) | "4,5-dihydro-6-(pyridinyl)-3(2h)-pyridazinone, wertvoll als kardiotonische mittel, und ihre herstellung" |