SU567405A3 - Способ получени гетероциклических соединений - Google Patents
Способ получени гетероциклических соединенийInfo
- Publication number
- SU567405A3 SU567405A3 SU7502169007A SU2169007A SU567405A3 SU 567405 A3 SU567405 A3 SU 567405A3 SU 7502169007 A SU7502169007 A SU 7502169007A SU 2169007 A SU2169007 A SU 2169007A SU 567405 A3 SU567405 A3 SU 567405A3
- Authority
- SU
- USSR - Soviet Union
- Prior art keywords
- thiomethyl
- aminoethyl
- bis
- ethyl
- mixture
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title description 13
- 238000002360 preparation method Methods 0.000 title description 5
- 238000000034 method Methods 0.000 title description 3
- 125000000623 heterocyclic group Chemical group 0.000 title 1
- 229910052757 nitrogen Inorganic materials 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- -1 methyl 5 - imidazolyl Chemical group 0.000 description 6
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 5
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 5
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 5
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 2
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
- 238000011097 chromatography purification Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- HNCSVMNWPGRJKP-UHFFFAOYSA-N (3-aminopyridin-2-yl)methanol Chemical compound NC1=CC=CN=C1CO HNCSVMNWPGRJKP-UHFFFAOYSA-N 0.000 description 1
- ZENKESXKWBIZCV-UHFFFAOYSA-N 2,2,4,4-tetrafluoro-1,3-benzodioxin-6-amine Chemical group O1C(F)(F)OC(F)(F)C2=CC(N)=CC=C21 ZENKESXKWBIZCV-UHFFFAOYSA-N 0.000 description 1
- WBRDXACHVMJSRH-UHFFFAOYSA-N 2-(1,2-oxazol-3-ylmethylsulfanyl)ethylthiourea Chemical compound NC(=S)NCCSCC=1C=CON=1 WBRDXACHVMJSRH-UHFFFAOYSA-N 0.000 description 1
- OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
- BRQHUXVGPNTWLO-UHFFFAOYSA-N 3-(1,3-oxazol-2-yl)propan-1-amine Chemical compound NCCCC1=NC=CO1 BRQHUXVGPNTWLO-UHFFFAOYSA-N 0.000 description 1
- VJSUMPPMFYQOMP-UHFFFAOYSA-N 4-(1h-imidazol-5-yl)butan-1-amine Chemical compound NCCCCC1=CNC=N1 VJSUMPPMFYQOMP-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 102100039875 Histone H3-7 Human genes 0.000 description 1
- 101001035307 Homo sapiens Histone H3-7 Proteins 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N aminothiocarboxamide Natural products NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- IULFXBLVJIPESI-UHFFFAOYSA-N bis(methylsulfanyl)methylidenecyanamide Chemical compound CSC(SC)=NC#N IULFXBLVJIPESI-UHFFFAOYSA-N 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 229940097265 cysteamine hydrochloride Drugs 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- LBVZYUZDHIPGLN-UHFFFAOYSA-N imidazol-1-ylmethanethiol Chemical compound SCN1C=CN=C1 LBVZYUZDHIPGLN-UHFFFAOYSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- GRFNBEZIAWKNCO-UHFFFAOYSA-N mhp Natural products OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
-
- 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
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/32—Sulfur atoms
-
- 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
- C07D213/60—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D233/68—Halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/46—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D275/00—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings
- C07D275/02—Heterocyclic compounds containing 1,2-thiazole or hydrogenated 1,2-thiazole rings not condensed with other rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
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)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
(54) СПОСОБ ПОЛУЧЕНИЯ ГЕТЕРОЦИКЛИЧЕСКИХ СОЕДИНЕНИЙ
последующей хроматографической очистки на колонке с силикагелем при элюировании смесью изопропилового спирта и эфира, а затем смесью изопропилового спирта и этанола получают 18 г целевого продукта с т.пл. 133-135° СJ, Найдено,%: С 47,0; Н6,1; N 22,0
Вычислено,%: С 46,8; Н 6,3; N 21,9.
П р и м е р 2. Получение N, N - бис - | 2 - (4 метил 5 - имидазолил) - метштгио - этил j мочевины.
Смесь 4 - метил - 5 - .(2 - аминозтил) гаометил - имидазола (8,55 г) и 1,1 - карбонила диимидазола (2,70 г) нагревают при 100° С 1ч. После охлаждени и обработки гор чей водой получают твердое вещество, которое отфильтровьгеают и промьюают последовательно.этанолом, водой и метанолом. После перекристаллизации из смеси метанола и зфира получают целевой продукт с т.пл. 225-228° С.
Найдено,%: С 48,6; Н6,7; N 22,3; S 17,4
С15Н24Мб052
Вычислено,%: С 48,9; Н 6,6; N 22,8; S 17,4.
Смесь 4 - метил 5 - (2 - аминоэтил). тиометил - имидазола (1,6 г) и 1,1 - карбонила диимидазола (0,5 г) в диметилформамиде(12мл) кип т т с обратным холодильником до затвердевани смеси. После охлаждени к ней добавл ют диметилформамид и получеьшую суспензию фильтруют . Получают твердый продукт, который промывают последовательно водой, этанолом и эфиром и перекристаллизовьшают из диметилформамида, выход 0,52 г, т.пл. 230-234° С.
П р и м е р 3. Получение W - циан N , N -бис - 2 - (4 - метил - 5 - имидазолил) метилтио - этил j - гуанидина.
а)Смесь 4 - метил - 5 - (2 - аминоэтил) тиометил - имидазола (1,71 г) и диметилциандигаоимидокарбоната (0,36 г) нагревают на водной бане 4ч. После добавлени ацетонитрила получают кристаллический продукт (0,9г); т.пл. 99-90°С.
б)Раствор 4 - метил - 5 - (2 - аминоэтил) тиометил - имидазола (6,8 г) и диметилцианднтиоимидокарбоната (1,36 г) в пиридине (6мл) кип т т с обратным холодильником 7 ч. После концентрировани и растирани с ацетонитрилом получают кристаллический , продукт (2,0 г), т.пл. 93-96° С.
П р и м е р 4. Получение N, N - бис - 4- (5 имидазолилбутил) - тиомочевины.
Раствор 4 - (4 - аминобутил) - имидазола (5,6 г) и сероуглерода (1,6 г) ,в этаноле (60мл) выдерживают при комнатной температуре 2 ч и кип т т с обратным холодильником 6ч. Остаток после концентрировани кристаллизуют из водного этанола, затем из смеси этанола с эфиром и получают твердый продукт (5,8 г), который перекристаллизовьшают из большого объема ацетонитрила и получают целевое соединение; тлл. 137-138°С.
Найдено,%: С 56,1; П 7,4; N 26,1; S 9,8
CisH24N6S
Вычислено,%: С 56,2; Н7,6; N26,2; 510,0.
П р и м е р 5. Получение N, N - бис г 2 - (3 бром 2 - йлшдадме-гилтил; -; этил - N циангуанидина.
Раствор нитрита натри (2,38 г) в воде (10 мл) по капл м добавл ют к перемешиваемой смеси 3 .амино - 2 - оксиметилпиридина (4,8 г), водной бромистоводородной кислоты (48%-на , 10 мл) и вх)ды (5 мл) при 0-5 С. Полученный раствор соли диазони добавл ют к гор чему раствору бромистой меди (1) (2,5 г) в 60%-ной бромистоводородной кислоте. После прекращени выделени азота смесь нагревают на вод ной: бане 1/2 ч, разбавл ют- в9дЬй--и насыщают -се едорвдом. 11оеле фильтровани , концентрирова1ш до небольщого объема и экстракции хлороформом получают 3 бром - 2 - оксиметйлпиридаш (4,8 г), который раствор ют в водной бромистоводородной кислоте (48%-на , 50 мл), к раствору добавл ют хлоргидрат цистеамина (3,22 г) и кип т т с обратным холодильншсом 6 ч. После концентрировани и перекристаллизации из вод1ного этанола получают дибромгидрат 2 - (2 - аминоэтил) - тиометил - 3 бромпиридина (6,1 г), т.пл. 252-254°С.
Найдено,%: С 23,6; Н 3,4; N 6,7; S 7,9
C8HiiBrN2S
Бычислено,о:С23,5; Н 3,2; N6,9; 57,8.
При реакции диметилциандитиоимидокарбоната с 2 - ((2 - аминоэтил) - тиометил - 3 - бромпиридином , проводимой как описано в примере 3 (6), получают целевое соединение (1,1 г); т.пл. 118119° С.
Найдено,%: С40,0; Н3,8; N15,9; Вг29,5; S 11,9
Cj8H2oN6Br2S2
Вычислено,%: С 39,7; Н3,7; N15,4; В г 29,4; 511,8.
П р и м е р 6. Получение N, N - бис - (2 - (2 пиридилметилтио ) - этил - N - циангуанидина.
При реакции 2 - (2 - иминоэтил) - тиометил пиридина с диметилциандитиоимидокарбонатбм, проводимой как описано в примере 3 (б), получают целевое соединение, т.пл. 78-80° С.
Пайдено,%: С 56,2; Н5,7; N 21,9; S 16,5
С18Н22 б32
Вычислено,%: С 55,9; Н5,7; N 21,7; 5 16,6.
П р и м е р 7. Получение N, N - бис - 2 - (2 тиазолилметилтио ) - этил - N - циангуанидина.
Раствор 2 - 1(2 - аминоэтил) - тиометил ттиаэола (1,7 г) и диметилциандитаоимидокарбоната (0,68 г) в пиридине (10 мл) нагревают на вод ной бане 6 ч, затем кип т т с обратным холодильником также 6 ч. После добавлени амина (0,3 г) нагревают с обратным холодильником еще 6 ч. После концентрировани и хроматографической очистки на колонке с силикагелем получают делевое соединение (0,25 г), т.пл. 66-68° С.
Найдено,: С 42,0; Н 4,6; N 21,0
С14Н18 б54
Вычислено,%; С 42,2; Н4,6; N21,1.
Примере. Получеш1е N - бензолсульфойил N ,N - бис - 2 -(4- метил - 5 - имидазолил) метилтио - этил - гуанидина.
Смесь 4 - метил - 5 - (2 - аминоэтил) тиометил - имидазола (4,7 г) и N - беизолсульфонилбисдиметилтиоимидокарбоната (3,6 г) нагревают при 140-150° С 1 ч. Полученный продукт хроматографируют на колонке с силикагелем и элюируют смесью этиладетата и этанола (3:2). По лучают стекловидный продукт (5,5 г), содержащий небольшое количество этанола.
Шйдено,%:.С49,6; Н5,8; S 13,3
С25 29 7О23з+1% этанола.
Вычислено,: С49,7; Н 5,8; S 18,7.
П р и м е р 9. Реакцией смеси 3 - (2 аминоэтил ) - тиометил - изотиазола и диметилциандитиоимидокарбоната в услови х аналогичных примеру 3 (б) получают N - циан - N , N - бис - (3 - изотиазолилметилтио) - этил - гуанидин.
При реакции следующих соединений:
3 - (2 - аминоэтил) - тиометил - изоксазола;
2 - (2 - аминоэтил) - тиометил - 1, 2, 4 триазола;
2 - (2 - аминоэтил) - тиометил - 5 - амино 1 ,3,4- тиадиазола и
2 - (2 - аминоэтил) - тиометил - 3 - оксипиридина аналогичным способом с диметилциандитиоимидокарбонатом получают соответственно следующие продукты:
N - циан - N , N - бнс - 2 - (3 изоксазолилметилтио ) этил. - гуанидин;
N - циан - N , N - бис - 2 - (3 - 1, 2, 4 триазолилметилтио ) - этил - гуанидин;
N - циан- N, N - бис - {2- ( 6 - амино 2 3 , 4- тиадазолил) - метилтио - этил - гуанидин;
N - циан - N , N - - 2- (3- окси - 2пиридил ) - метилтио - этил j - гуанидин.
Пример 10. При реакции 2 - (3 - аминопропил ) - оксазола и диметилциандитиоимидокарбоната в услови х примера 3 (б) получают N - циан N , N - бис - 3 - (2 - оксазолил) - тиопропил гуанидин .
Пример 1. При реакции 4 - 2 - (2 аминоэтил ) - тиоэтил - имидазола и диметилциандитиоимидокарбоната в услови х примера 3 (б)
получают N - циан - N , N - бис - 2 - 2 - (4 имидаэолил ) - этил - тиоэтил J - гуанидин.
П р и м е р 12. В услови х примера 1 с применением в качестве исходных продуктов сероуглерода и 3 - (2 - аминоэтил) - тиометил изоксазола или 2 - (2 - аминоэтил) - тиометил - 3 .- оксипиридина получают N , N - 5ис 2 - (3 изоксазолилметилтио ) - этил - тиомочевину или N , N - бис - 2 - (3 - окси - 2 - пиридил) метилтио - этил - тиомочевину.
гле У - е р 13. При реакции 4 - метил - 5 - (2 аминоэтил ) - тиометил - имидазола и N - метансульфонилбисдиметилтиоимидокарбоната в услови х примера 8 получают N - метансульфонил - N ,
N - бис - J 2 - (4 - метил - 5 - имиддзолил) метилтио - ЭТИЛ} - гуанидин.
Формула,изобретени
20
Способ получени гетероциклических соединений общей формулы (I)
(RiNH),
где RI - грущ1а формулы Het25 (CH2)mZ(CH2)n, Het - имидазол, ниридин,
тиазол, изотиазол, оксазол, изооксазол, триазол шти
тиадиазол, возможно замещенный алкилом Cj-С4,
гидроксилом, галоидом или аминогруппой;
Z - сера или метилен; 30т-0,1 или 2;
П - 2 или 3 при условии, гго гл + П - 3 или 4:.
X - сера, кислород или группа NY, где У циан или SOjRj. где Rj - алкил Ci-C4 или фенил; 35отличающийс тем, что соединение общей формулы (И) ,,
где Е - сера, группа (AS) 2, А - алкил Ci-C4, или (имидазолил) 2; подвергают взаимодействию с 40 амином общей формулы (III)
RiNH2
где RI имеет указанные значени , при 20-160° С.
Источники информации, прин тые во внимание при экспертизе:
1. Houben-Weyl. Methoden der ofganischen Chemie. - G. Thieme Verlag. Stutgart, Band IX, 1955,885.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB3342873A GB1431589A (en) | 1973-07-13 | 1973-07-13 | Ureas, thioureas and guanidines n,n-disubstituted by heterocyclo- alkylene and/or heterocycloalkylenethioalkylene groups |
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| Application Number | Title | Priority Date | Filing Date |
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| SU2043788A SU559647A3 (ru) | 1973-07-13 | 1974-07-12 | Способ получени гетероциклических соединений |
| SU7502168215A SU571193A3 (ru) | 1973-07-13 | 1975-09-04 | Способ получени производных гуанидина |
| SU7502169007A SU567405A3 (ru) | 1973-07-13 | 1975-09-05 | Способ получени гетероциклических соединений |
Family Applications Before (2)
| Application Number | Title | Priority Date | Filing Date |
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| SU2043788A SU559647A3 (ru) | 1973-07-13 | 1974-07-12 | Способ получени гетероциклических соединений |
| SU7502168215A SU571193A3 (ru) | 1973-07-13 | 1975-09-04 | Способ получени производных гуанидина |
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| US (1) | US4499101A (ru) |
| JP (1) | JPS5830314B2 (ru) |
| AR (3) | AR204928A1 (ru) |
| AT (1) | AT346855B (ru) |
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| BG (1) | BG25792A3 (ru) |
| CA (1) | CA1049524A (ru) |
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| DK (1) | DK334674A (ru) |
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| ES (3) | ES428246A1 (ru) |
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| NO (1) | NO143063C (ru) |
| OA (1) | OA04814A (ru) |
| PH (1) | PH11618A (ru) |
| PL (3) | PL96460B1 (ru) |
| SE (1) | SE416202B (ru) |
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Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4215125A (en) * | 1973-07-13 | 1980-07-29 | Smith Kline & French Laboratories Limited | Pyridyl ureas, thioureas and guanidines |
| US4070472A (en) * | 1974-02-07 | 1978-01-24 | Smith Kline & French Laboratories Limited | Guanidino, thioureido, isothioureido and nitrovinylamino derivatives of pyridine |
| US4151289A (en) | 1975-01-22 | 1979-04-24 | Smith Kline & French Laboratories Limited | Nitromethylene amidino derivatives containing imidazole groups |
| GB1542840A (en) * | 1975-02-03 | 1979-03-28 | Smith Kline French Lab | Heterocyclic dithiocarbamates and isothioureas |
| US4120972A (en) | 1975-02-03 | 1978-10-17 | Smith Kline & French Laboratories Limited | Imidazolylmethylthio-ethyl isothiourea compounds |
| IL49528A (en) * | 1975-05-21 | 1980-11-30 | Smith Kline French Lab | Imidazolyl(or thiazolyl)methylthio(or butyl)guanidine or thiourea derivatives,their preparation and pharmaceutical compositions comprising them |
| US4165378A (en) | 1977-04-20 | 1979-08-21 | Ici Americas Inc. | Guanidine derivatives of imidazoles and thiazoles |
| ZA782129B (en) | 1977-04-20 | 1979-03-28 | Ici Ltd | Hertocyclic derivatives |
| US4233302A (en) | 1977-12-23 | 1980-11-11 | Glaxo Group Limited | Amine derivatives and pharmaceutical compositions containing them |
| US4309435A (en) | 1978-10-16 | 1982-01-05 | Imperial Chemical Industries Ltd. | Antisecretory guanidine derivatives and pharmaceutical compositions containing them |
| DE3069889D1 (en) | 1979-01-18 | 1985-02-14 | Ici Plc | Guanidine derivatives, processes for their manufacture and pharmaceutical compositions containing them |
| JPS5610175A (en) * | 1979-07-06 | 1981-02-02 | Fujisawa Pharmaceut Co Ltd | Preparation of imidazole derivative |
| JPS5775975A (en) * | 1980-08-27 | 1982-05-12 | Glaxo Group Ltd | Heterocyclic derivative, manufacture and medicinal composition containing same |
| DE3366369D1 (en) * | 1982-03-17 | 1986-10-30 | Smith Kline French Lab | Pyridine derivatives |
| DE3579000D1 (de) | 1985-04-02 | 1990-09-06 | Heumann Pharma Gmbh & Co | Imidazolylalkylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel. |
| DE3512084A1 (de) * | 1985-04-02 | 1986-10-09 | Ludwig Heumann & Co GmbH, 8500 Nürnberg | Guanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| DE3631334A1 (de) * | 1986-09-15 | 1988-03-17 | Heumann Pharma Gmbh & Co | Neue imidazolylguanidinderivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel |
| NL9100365A (nl) * | 1991-02-27 | 1992-09-16 | Seed Capital Investments | Imidazoolderivaten met agonistische of antagonistische activiteit op de histamine h3-receptor. |
| DE69222757T2 (de) * | 1991-02-27 | 1998-02-12 | Seed Capital Investments | Imidazol-derivate mit antagonistischer aktivität auf den histamin-h3-receptor |
| EP1032556B1 (en) * | 1997-10-21 | 2007-12-19 | Wyeth a Corporation of the State of Delaware | Pharmaceutically active compounds and methods of use |
| US7041702B1 (en) | 1997-10-21 | 2006-05-09 | Scion Pharmaceuticals, Inc. | Pharmaceutically active compounds and methods of use |
| EP4196793A1 (en) | 2020-08-11 | 2023-06-21 | Université de Strasbourg | H2 blockers targeting liver macrophages for the prevention and treatment of liver disease and cancer |
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| NL292485A (ru) * | 1962-05-09 | |||
| CH484918A (de) * | 1965-10-28 | 1970-01-31 | Ciba Geigy | Verfahren zur Herstellung heterocyclischer, Aethylendoppelbindungen enthaltender Verbindungen |
| US3770755A (en) * | 1967-09-26 | 1973-11-06 | Ici Ltd | 4-(4-bromophenyl)-2-(2-hydroxysopropyl) thiazole |
| US3868457A (en) * | 1969-10-29 | 1975-02-25 | Smith Kline French Lab | Method of inhibiting histamine activity with guanidine compounds |
| BE758146A (fr) * | 1969-10-29 | 1971-04-28 | Smith Kline French Lab | Derives de l'amidine |
| US3749728A (en) * | 1972-02-15 | 1973-07-31 | Smith Kline French Lab | N-cycloalkyl and n-cycloalkane-alkylthioamides |
| US3821229A (en) * | 1972-12-07 | 1974-06-28 | American Cyanamid Co | Diquaternary salts of di-4-pyridyl ketone |
| US4013659A (en) * | 1973-07-13 | 1977-03-22 | Smith Kline & French Laboratories Limited | Certain n,n'-disubstituted guanidine compounds and their use |
| US4154838A (en) * | 1975-07-31 | 1979-05-15 | Smith Kline & French Laboratories Limited | Alkoxy pyridine |
-
1973
- 1973-07-13 GB GB3342873A patent/GB1431589A/en not_active Expired
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- 1974-06-28 FR FR7422670A patent/FR2274298A1/fr active Granted
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