DE2336678A1 - Pyridinderivate, verfahren zu deren herstellung und diese enthaltende therapeutische zusammensetzungen - Google Patents
Pyridinderivate, verfahren zu deren herstellung und diese enthaltende therapeutische zusammensetzungenInfo
- Publication number
- DE2336678A1 DE2336678A1 DE19732336678 DE2336678A DE2336678A1 DE 2336678 A1 DE2336678 A1 DE 2336678A1 DE 19732336678 DE19732336678 DE 19732336678 DE 2336678 A DE2336678 A DE 2336678A DE 2336678 A1 DE2336678 A1 DE 2336678A1
- Authority
- DE
- Germany
- Prior art keywords
- acid
- days
- pyrimethamine
- acid addition
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims description 7
- 230000001225 therapeutic effect Effects 0.000 title claims description 6
- 238000004519 manufacturing process Methods 0.000 title claims description 4
- 239000000203 mixture Substances 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims description 42
- -1 tripropylacetyl Chemical group 0.000 claims description 21
- 239000002585 base Substances 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 13
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 239000012458 free base Substances 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 150000003230 pyrimidines Chemical class 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 6
- 229940083082 pyrimidine derivative acting on arteriolar smooth muscle Drugs 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000006408 oxalic acid Nutrition 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims 3
- 125000004918 2-methyl-2-pentyl group Chemical group CC(C)(CCC)* 0.000 claims 1
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 39
- 229960000611 pyrimethamine Drugs 0.000 description 39
- 241001465754 Metazoa Species 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- RGEWLKLRTWXPDT-UHFFFAOYSA-N n-[5-(4-chlorophenyl)-6-ethyl-2-(2-propylpentanoylamino)pyrimidin-4-yl]-2-propylpentanamide Chemical compound CCCC(CCC)C(=O)NC1=NC(NC(=O)C(CCC)CCC)=NC(CC)=C1C1=CC=C(Cl)C=C1 RGEWLKLRTWXPDT-UHFFFAOYSA-N 0.000 description 21
- 238000002474 experimental method Methods 0.000 description 14
- 244000045947 parasite Species 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 238000002255 vaccination Methods 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- 241000699670 Mus sp. Species 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- 238000007912 intraperitoneal administration Methods 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- 231100000517 death Toxicity 0.000 description 8
- 230000034994 death Effects 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 201000010099 disease Diseases 0.000 description 7
- 238000001953 recrystallisation Methods 0.000 description 6
- 150000008064 anhydrides Chemical class 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 230000003449 preventive effect Effects 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 201000005485 Toxoplasmosis Diseases 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108010058846 Ovalbumin Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000842 anti-protozoal effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000009109 curative therapy Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 201000004792 malaria Diseases 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 229940092253 ovalbumin Drugs 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- CQVKMVQRSNNAGO-UHFFFAOYSA-N 2-[4-formyl-3-methyl-n-(2-methylsulfonyloxyethyl)anilino]ethyl methanesulfonate Chemical compound CC1=CC(N(CCOS(C)(=O)=O)CCOS(C)(=O)=O)=CC=C1C=O CQVKMVQRSNNAGO-UHFFFAOYSA-N 0.000 description 2
- GYIUDLLQLVWKPP-UHFFFAOYSA-N 2-propylpentanoyl 2-propylpentanoate Chemical compound CCCC(CCC)C(=O)OC(=O)C(CCC)CCC GYIUDLLQLVWKPP-UHFFFAOYSA-N 0.000 description 2
- 241000700198 Cavia Species 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000009182 Parasitemia Diseases 0.000 description 2
- 208000030852 Parasitic disease Diseases 0.000 description 2
- 241000224016 Plasmodium Species 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 206010070834 Sensitisation Diseases 0.000 description 2
- 239000003904 antiprotozoal agent Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 230000002489 hematologic effect Effects 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000000644 isotonic solution Substances 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 231100000053 low toxicity Toxicity 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
- 210000004303 peritoneum Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 230000008313 sensitization Effects 0.000 description 2
- 230000035939 shock Effects 0.000 description 2
- 238000010583 slow cooling Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 150000003456 sulfonamides Chemical class 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- AMVGQNFLBRUCGF-UHFFFAOYSA-N (7-amino-2-methylphenoxazin-3-ylidene)-dimethylazanium;chloride Chemical compound [Cl-].C1=C(N)C=C2OC3=CC(=[N+](C)C)C(C)=CC3=NC2=C1 AMVGQNFLBRUCGF-UHFFFAOYSA-N 0.000 description 1
- PITHYUDHKJKJNQ-UHFFFAOYSA-N 2-propylpentanoyl chloride Chemical compound CCCC(C(Cl)=O)CCC PITHYUDHKJKJNQ-UHFFFAOYSA-N 0.000 description 1
- YEAICDDXRUOCKJ-UHFFFAOYSA-N 4-amino-n-pyrazin-2-ylbenzenesulfonamide Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=CN=CC=N1 YEAICDDXRUOCKJ-UHFFFAOYSA-N 0.000 description 1
- JZCLIFPQURTYFA-UHFFFAOYSA-N 5-(4-chlorophenyl)-6-ethylpyrimidine-2,4-diamine;hydrochloride Chemical compound Cl.CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 JZCLIFPQURTYFA-UHFFFAOYSA-N 0.000 description 1
- NALREUIWICQLPS-UHFFFAOYSA-N 7-imino-n,n-dimethylphenothiazin-3-amine;hydrochloride Chemical compound [Cl-].C1=C(N)C=C2SC3=CC(=[N+](C)C)C=CC3=NC2=C1 NALREUIWICQLPS-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 206010003445 Ascites Diseases 0.000 description 1
- 206010006895 Cachexia Diseases 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 241000287828 Gallus gallus Species 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
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 241000224017 Plasmodium berghei Species 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 208000035415 Reinfection Diseases 0.000 description 1
- 102000006382 Ribonucleases Human genes 0.000 description 1
- 108010083644 Ribonucleases Proteins 0.000 description 1
- 229920002472 Starch Polymers 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
- 229930006000 Sucrose Natural products 0.000 description 1
- 241000223996 Toxoplasma Species 0.000 description 1
- 241000223997 Toxoplasma gondii Species 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000013330 chicken meat Nutrition 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 210000005069 ears Anatomy 0.000 description 1
- 208000026500 emaciation Diseases 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000007925 intracardiac injection Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 231100000682 maximum tolerated dose Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 231100000916 relative toxicity Toxicity 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 206010043089 tachypnoea Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB3437872A GB1384150A (en) | 1972-07-21 | 1972-07-21 | Pyrimidine derivatives and process for preparing the same |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2336678A1 true DE2336678A1 (de) | 1974-01-31 |
Family
ID=10364909
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19732336678 Pending DE2336678A1 (de) | 1972-07-21 | 1973-07-19 | Pyridinderivate, verfahren zu deren herstellung und diese enthaltende therapeutische zusammensetzungen |
Country Status (21)
| Country | Link |
|---|---|
| JP (1) | JPS4980082A (https=) |
| AR (1) | AR197241A1 (https=) |
| AT (1) | AT326671B (https=) |
| AU (1) | AU470607B2 (https=) |
| BE (1) | BE802451A (https=) |
| CA (1) | CA986518A (https=) |
| CH (1) | CH579552A5 (https=) |
| DE (1) | DE2336678A1 (https=) |
| DK (1) | DK131626C (https=) |
| ES (1) | ES417142A1 (https=) |
| FR (1) | FR2193604B1 (https=) |
| GB (1) | GB1384150A (https=) |
| HU (1) | HU167313B (https=) |
| IE (1) | IE38033B1 (https=) |
| NL (1) | NL7309988A (https=) |
| NO (1) | NO137691C (https=) |
| OA (1) | OA04539A (https=) |
| SE (1) | SE399556B (https=) |
| SU (1) | SU468422A3 (https=) |
| YU (1) | YU180673A (https=) |
| ZA (1) | ZA734406B (https=) |
-
1972
- 1972-07-21 GB GB3437872A patent/GB1384150A/en not_active Expired
-
1973
- 1973-06-28 ZA ZA734406A patent/ZA734406B/xx unknown
- 1973-06-29 AR AR248838A patent/AR197241A1/es active
- 1973-06-29 IE IE1093/73A patent/IE38033B1/xx unknown
- 1973-07-02 YU YU01806/73A patent/YU180673A/xx unknown
- 1973-07-04 AU AU57699/73A patent/AU470607B2/en not_active Expired
- 1973-07-05 AT AT591673A patent/AT326671B/de not_active IP Right Cessation
- 1973-07-17 BE BE133575A patent/BE802451A/xx unknown
- 1973-07-18 NL NL7309988A patent/NL7309988A/xx unknown
- 1973-07-19 DE DE19732336678 patent/DE2336678A1/de active Pending
- 1973-07-19 SE SE7310102A patent/SE399556B/xx unknown
- 1973-07-20 HU HULA829A patent/HU167313B/hu unknown
- 1973-07-20 CA CA176990A patent/CA986518A/en not_active Expired
- 1973-07-20 DK DK404273A patent/DK131626C/da active
- 1973-07-20 NO NO2951/73A patent/NO137691C/no unknown
- 1973-07-20 OA OA54970A patent/OA04539A/xx unknown
- 1973-07-20 FR FR7326645A patent/FR2193604B1/fr not_active Expired
- 1973-07-20 CH CH1066673A patent/CH579552A5/xx not_active IP Right Cessation
- 1973-07-20 SU SU1939807A patent/SU468422A3/ru active
- 1973-07-21 JP JP48082371A patent/JPS4980082A/ja active Pending
- 1973-07-21 ES ES417142A patent/ES417142A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| BE802451A (fr) | 1974-01-17 |
| NO137691C (no) | 1978-04-05 |
| DK131626B (da) | 1975-08-11 |
| NO137691B (no) | 1977-12-27 |
| HU167313B (https=) | 1975-09-27 |
| AR197241A1 (es) | 1974-03-22 |
| ES417142A1 (es) | 1976-03-01 |
| IE38033B1 (en) | 1977-12-07 |
| CH579552A5 (https=) | 1976-09-15 |
| SU468422A3 (ru) | 1975-04-25 |
| IE38033L (en) | 1974-01-21 |
| YU180673A (en) | 1980-04-30 |
| GB1384150A (en) | 1975-02-19 |
| FR2193604B1 (https=) | 1977-01-28 |
| ATA591673A (de) | 1975-03-15 |
| JPS4980082A (https=) | 1974-08-02 |
| CA986518A (en) | 1976-03-30 |
| FR2193604A1 (https=) | 1974-02-22 |
| NL7309988A (https=) | 1974-01-23 |
| DK131626C (da) | 1976-01-19 |
| AT326671B (de) | 1975-12-29 |
| ZA734406B (en) | 1974-06-26 |
| AU470607B2 (en) | 1976-03-25 |
| AU5769973A (en) | 1975-01-09 |
| OA04539A (fr) | 1980-03-30 |
| SE399556B (sv) | 1978-02-20 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DD148951A5 (de) | Verfahren zur herstellung virozider aminderivate | |
| DE2634288A1 (de) | Benzylidenderivate, verfahren zu ihrer herstellung und sie enthaltende arzneimittel | |
| DE2414273C3 (de) | N-Methyl-D-glucaminsalz von 2-(2'-Methyl-3'-trifluormethyl-anilin)-nicotinsäure, Verfahren zu seiner Herstellung und es enthaltende Arzneimittelzubereitung | |
| DE1949813A1 (de) | Substituierte Pyrazole | |
| DE2118109A1 (de) | Neue chemische Verbindung | |
| DE2449205C2 (de) | Substituierte Furylverbindungen, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel | |
| DE2427272C3 (de) | 1-(2-(β-Naphthyloxy)-äthyl)-3-methyl -pyrazolon-(5), Verfahren sowie Verwendung als Antithrombotikum | |
| DE2140865B2 (de) | 1 -Imidazolyl-methanphosphonsäureester, Verfahren zu ihrer Herstellung sowie diese enthaltende Arzneimittel | |
| DE2242787C2 (de) | 4-Phenyl-6-amino-3,4-dihydropyridon-(2)-3,5-dicarbonsäure-diäthylesterderivate, ein Verfahren zu deren Herstellung und diese enthaltende Arzneimittel | |
| DE2336678A1 (de) | Pyridinderivate, verfahren zu deren herstellung und diese enthaltende therapeutische zusammensetzungen | |
| DE2036935B2 (de) | Diisonicotinsaeurehydrazid-methansulfonat des d(+)2,2'-(aethylendiimino)-di-l- butanols, verfahren zur herstellung desselben und diese verbindung enthaltende arzneimittel | |
| DE2403786A1 (de) | Neue derivate der cumarine | |
| DE2238304C3 (de) | (Choleretisch wirksame) Ester bzw. Salze von Dehydrocholsäure, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneipräparate | |
| DE2332733A1 (de) | Psychotherapeutisch wirksame 2-aminothiazolabkoemmlinge und diese enthaltende arzneimittel | |
| CH643831A5 (de) | Cinnamyl-moranolin-derivate. | |
| DE3043446C2 (https=) | ||
| DE1670539C3 (de) | Diacylthiamine und Verfahren zu deren Herstellung | |
| DE2237732C2 (de) | trans-1-(3-Benzoyloxystyryl)-pyridiniumsalze und ihre Verwendung | |
| DE1695649A1 (de) | Pyrrolidinol- oder -thiolverbindungen und Verfahren zu deren Herstellung | |
| DE2713745A1 (de) | Doxorubicinthioester und verfahren zu deren herstellung | |
| DE2013267C3 (de) | Vitamin-B tief 1-Disulfid-Di-nicotinat | |
| DE1593970C3 (de) | Homoargininpolymere und Verfahren zu ihrer Herstellung | |
| DE2213044C3 (de) | Racemisches und optisch aktives 1 -(23-Dichlorphenoxy)-3-tert. - butylamino-2-propanol und ihre Salze, Verfahren zu deren Herstellung und Arzneimittel auf Basis dieser Verbindungen | |
| AT372082B (de) | Verfahren zur herstellung von neuen aminderivaten von propandiolaethern | |
| DE2749075A1 (de) | Quaternaere 1-methyl-2-(phenothiazin- 10-yl)-aethylammoniumsalze und diese enthaltende arzneimittel |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| OHA | Expiration of time for request for examination |