CA1209919A - Pharmaceutical methods and compositions - Google Patents

Pharmaceutical methods and compositions

Info

Publication number: CA1209919A
Authority: CA; Canada
Prior art keywords: alkyl; thiadiazole; dioxide; independently; hydrogen
Prior art date: 1982-07-12
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.): Expired

Application number

CA000432026A

Other languages

English (en)

French (fr)

Inventor

Robert L. Cavanagh

Maxwell Gordon

Joseph P. Buyniski

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Co

Original Assignee

Bristol Myers Co

Priority date (The priority date 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 date listed.)

1982-07-12

Filing date

1983-07-07

Publication date

1986-08-19

1983-07-07 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1986-08-19 Application granted granted Critical

1986-08-19 Publication of CA1209919A publication Critical patent/CA1209919A/en

Status Expired legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims description 71
238000000034 method Methods 0.000 title description 103
229950000964 pepstatin Drugs 0.000 claims abstract description 79
108010091212 pepstatin Proteins 0.000 claims abstract description 78
FAXGPCHRFPCXOO-LXTPJMTPSA-N pepstatin A Chemical compound OC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)C[C@H](O)[C@H](CC(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)CC(C)C FAXGPCHRFPCXOO-LXTPJMTPSA-N 0.000 claims abstract description 78
238000011282 treatment Methods 0.000 claims abstract description 20
150000001875 compounds Chemical class 0.000 claims description 266
-1 hydroxy, amino Chemical group 0.000 claims description 169
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 147
125000000217 alkyl group Chemical group 0.000 claims description 143
229910052739 hydrogen Inorganic materials 0.000 claims description 74
239000001257 hydrogen Substances 0.000 claims description 70
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 35
150000003839 salts Chemical class 0.000 claims description 33
125000001424 substituent group Chemical group 0.000 claims description 30
125000003342 alkenyl group Chemical group 0.000 claims description 29
125000003545 alkoxy group Chemical group 0.000 claims description 27
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 27
239000012453 solvate Substances 0.000 claims description 26
125000000304 alkynyl group Chemical group 0.000 claims description 24
125000004076 pyridyl group Chemical group 0.000 claims description 23
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
231100000252 nontoxic Toxicity 0.000 claims description 22
230000003000 nontoxic effect Effects 0.000 claims description 22
239000002253 acid Substances 0.000 claims description 21
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
229910052717 sulfur Inorganic materials 0.000 claims description 17
239000011593 sulfur Substances 0.000 claims description 17
125000003282 alkyl amino group Chemical group 0.000 claims description 16
229910052757 nitrogen Inorganic materials 0.000 claims description 14
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
208000008469 Peptic Ulcer Diseases 0.000 claims description 11
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
239000001301 oxygen Chemical group 0.000 claims description 11
229910052760 oxygen Inorganic materials 0.000 claims description 11
230000002401 inhibitory effect Effects 0.000 claims description 10
230000001175 peptic effect Effects 0.000 claims description 10
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 8
239000005977 Ethylene Substances 0.000 claims description 8
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 8
125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 8
239000002552 dosage form Substances 0.000 claims description 7
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
125000002541 furyl group Chemical group 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000000335 thiazolyl group Chemical group 0.000 claims description 6
125000001544 thienyl group Chemical group 0.000 claims description 6
230000000026 anti-ulcerogenic effect Effects 0.000 claims description 5
125000001589 carboacyl group Chemical group 0.000 claims description 5
125000002883 imidazolyl group Chemical group 0.000 claims description 5
125000002971 oxazolyl group Chemical group 0.000 claims description 5
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 4
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 4
125000004093 cyano group Chemical group *C#N 0.000 claims description 4
125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
125000001113 thiadiazolyl group Chemical group 0.000 claims description 4
DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical group S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims description 3
125000001786 isothiazolyl group Chemical group 0.000 claims description 3
125000000842 isoxazolyl group Chemical group 0.000 claims description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
125000001425 triazolyl group Chemical group 0.000 claims description 3
150000002431 hydrogen Chemical group 0.000 claims 13
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 13
SYGWYBOJXOGMRU-UHFFFAOYSA-N chembl233051 Chemical compound C1=CC=C2C3=CC(C(N(CCN(C)C)C4=O)=O)=C5C4=CC=CC5=C3SC2=C1 SYGWYBOJXOGMRU-UHFFFAOYSA-N 0.000 claims 2
XLMCTHGDIZFBND-UHFFFAOYSA-N 3-n-[2-[[5-[(dimethylamino)methyl]furan-2-yl]methylsulfanyl]ethyl]-1,2,5-thiadiazole-3,4-diamine Chemical compound O1C(CN(C)C)=CC=C1CSCCNC1=NSN=C1N XLMCTHGDIZFBND-UHFFFAOYSA-N 0.000 claims 1
241001465754 Metazoa Species 0.000 abstract description 30
102000057297 Pepsin A Human genes 0.000 abstract description 20
108090000284 Pepsin A Proteins 0.000 abstract description 20
229940111202 pepsin Drugs 0.000 abstract description 19
230000000694 effects Effects 0.000 abstract description 15
239000003485 histamine H2 receptor antagonist Substances 0.000 abstract description 9
229940122957 Histamine H2 receptor antagonist Drugs 0.000 abstract description 8
230000000767 anti-ulcer Effects 0.000 abstract description 6
230000003247 decreasing effect Effects 0.000 abstract description 5
239000008139 complexing agent Substances 0.000 abstract description 3
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 478
239000000243 solution Substances 0.000 description 222
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 155
230000002829 reductive effect Effects 0.000 description 118
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 95
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 95
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 87
239000000047 product Substances 0.000 description 86
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 83
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 75
239000011541 reaction mixture Substances 0.000 description 70
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 64
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 63
229910001868 water Inorganic materials 0.000 description 63
239000000725 suspension Substances 0.000 description 62
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
229960001866 silicon dioxide Drugs 0.000 description 49
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
239000000741 silica gel Substances 0.000 description 48
229910002027 silica gel Inorganic materials 0.000 description 48
JGUPTNIZOBZUON-UHFFFAOYSA-N 3,4-dimethoxy-1,2,5-thiadiazole Chemical compound COC1=NSN=C1OC JGUPTNIZOBZUON-UHFFFAOYSA-N 0.000 description 41
238000003756 stirring Methods 0.000 description 41
238000010828 elution Methods 0.000 description 39
239000005457 ice water Substances 0.000 description 38
238000001953 recrystallisation Methods 0.000 description 38
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 37
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 37
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 34
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical class CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 33
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 28
WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 24
150000002500 ions Chemical class 0.000 description 22
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 21
229910000041 hydrogen chloride Inorganic materials 0.000 description 21
UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 20
QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical group [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 19
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 18
241000700159 Rattus Species 0.000 description 18
125000006308 propyl amino group Chemical group 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 17
229960001760 dimethyl sulfoxide Drugs 0.000 description 17
230000002496 gastric effect Effects 0.000 description 17
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 17
239000007787 solid Substances 0.000 description 17
238000012360 testing method Methods 0.000 description 17
238000010992 reflux Methods 0.000 description 16
241001024304 Mino Species 0.000 description 15
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 14
229960000620 ranitidine Drugs 0.000 description 14
VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 14
238000001228 spectrum Methods 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
208000025865 Ulcer Diseases 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
239000000499 gel Substances 0.000 description 12
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 12
229910021529 ammonia Inorganic materials 0.000 description 11
JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 11
101150041968 CDC13 gene Proteins 0.000 description 10
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 10
AQIXAKUUQRKLND-UHFFFAOYSA-N cimetidine Chemical compound N#C/N=C(/NC)NCCSCC=1N=CNC=1C AQIXAKUUQRKLND-UHFFFAOYSA-N 0.000 description 10
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 10
239000000523 sample Substances 0.000 description 10
230000028327 secretion Effects 0.000 description 10
239000000377 silicon dioxide Substances 0.000 description 10
210000002784 stomach Anatomy 0.000 description 10
125000000446 sulfanediyl group Chemical group *S* 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
231100000397 ulcer Toxicity 0.000 description 10
OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 9
241000282472 Canis lupus familiaris Species 0.000 description 9
230000015572 biosynthetic process Effects 0.000 description 9
229960001380 cimetidine Drugs 0.000 description 9
238000003818 flash chromatography Methods 0.000 description 9
239000012074 organic phase Substances 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
AUALQMFGWLZREY-UHFFFAOYSA-N acetonitrile;methanol Chemical compound OC.CC#N AUALQMFGWLZREY-UHFFFAOYSA-N 0.000 description 8
230000003628 erosive effect Effects 0.000 description 8
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 8
230000036961 partial effect Effects 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
206010017865 Gastritis erosive Diseases 0.000 description 7
229940094070 ambien Drugs 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
238000004458 analytical method Methods 0.000 description 7
125000004432 carbon atom Chemical group C* 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
238000004440 column chromatography Methods 0.000 description 7
231100000673 dose–response relationship Toxicity 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000003814 drug Substances 0.000 description 7
239000000706 filtrate Substances 0.000 description 7
238000001914 filtration Methods 0.000 description 7
239000006260 foam Substances 0.000 description 7
239000007789 gas Substances 0.000 description 7
238000010438 heat treatment Methods 0.000 description 7
230000036515 potency Effects 0.000 description 7
230000003389 potentiating effect Effects 0.000 description 7
ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 7
SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 6
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
UFULAYFCSOUIOV-UHFFFAOYSA-N cysteamine Chemical compound NCCS UFULAYFCSOUIOV-UHFFFAOYSA-N 0.000 description 6
229940097265 cysteamine hydrochloride Drugs 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
238000007912 intraperitoneal administration Methods 0.000 description 6
TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 6
239000012071 phase Substances 0.000 description 6
238000000746 purification Methods 0.000 description 6
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 5
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 5
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 5
KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 5
239000002585 base Substances 0.000 description 5
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 5
210000004211 gastric acid Anatomy 0.000 description 5
230000004044 response Effects 0.000 description 5
239000011734 sodium Substances 0.000 description 5
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 4
ZRSLQBDTGLCFJJ-UHFFFAOYSA-N 3,4-dimethoxy-1,2,5-thiadiazole 1,1-dioxide Chemical compound COC1=NS(=O)(=O)N=C1OC ZRSLQBDTGLCFJJ-UHFFFAOYSA-N 0.000 description 4
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 4
VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 4
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
230000009471 action Effects 0.000 description 4
239000000538 analytical sample Substances 0.000 description 4
239000005557 antagonist Substances 0.000 description 4
230000001262 anti-secretory effect Effects 0.000 description 4
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
239000003610 charcoal Substances 0.000 description 4
239000012043 crude product Substances 0.000 description 4
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 4
239000000284 extract Substances 0.000 description 4
FUKUFMFMCZIRNT-UHFFFAOYSA-N hydron;methanol;chloride Chemical compound Cl.OC FUKUFMFMCZIRNT-UHFFFAOYSA-N 0.000 description 4
230000006872 improvement Effects 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
230000003902 lesion Effects 0.000 description 4
239000012280 lithium aluminium hydride Substances 0.000 description 4
229960003151 mercaptamine Drugs 0.000 description 4
UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 4
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 4
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MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
238000012353 t test Methods 0.000 description 1
238000012956 testing procedure Methods 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
UBBZKZRMWONRRS-UHFFFAOYSA-N thionyl dichloride hydrochloride Chemical compound Cl.ClS(Cl)=O UBBZKZRMWONRRS-UHFFFAOYSA-N 0.000 description 1
AWLILQARPMWUHA-UHFFFAOYSA-M thiopental sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC([S-])=NC1=O AWLILQARPMWUHA-UHFFFAOYSA-M 0.000 description 1
AIUHRQHVWSUTGJ-UHFFFAOYSA-N thiopropazate Chemical compound C1CN(CCOC(=O)C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 AIUHRQHVWSUTGJ-UHFFFAOYSA-N 0.000 description 1
229960004728 thiopropazate Drugs 0.000 description 1
238000004448 titration Methods 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
231100000440 toxicity profile Toxicity 0.000 description 1
229940125725 tranquilizer Drugs 0.000 description 1
239000003204 tranquilizing agent Substances 0.000 description 1
230000002936 tranquilizing effect Effects 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
229940086542 triethylamine Drugs 0.000 description 1
210000001113 umbilicus Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
210000002417 xiphoid bone Anatomy 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000432026A 1982-07-12 1983-07-07 Pharmaceutical methods and compositions Expired CA1209919A (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US39727182A	1982-07-12	1982-07-12
US397,271		1982-07-12
DK010684A DK165545C (da)	1982-07-12	1984-01-10	Farmaceutisk praeparat til behandling af peptisk ulcus paa enhedsdosisform

Publications (1)

Publication Number	Publication Date
CA1209919A true CA1209919A (en)	1986-08-19

Family

ID=26063313

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000432026A Expired CA1209919A (en)	1982-07-12	1983-07-07	Pharmaceutical methods and compositions

Country Status (2)

Country	Link
CA (1)	CA1209919A (da)
DK (2)	DK318683D0 (da)

1983
- 1983-07-07 CA CA000432026A patent/CA1209919A/en not_active Expired
- 1983-07-11 DK DK3186/83A patent/DK318683D0/da not_active Application Discontinuation
1984
- 1984-01-10 DK DK010684A patent/DK165545C/da not_active IP Right Cessation

Also Published As

Publication number	Publication date
DK165545C (da)	1993-05-03
DK10684A (da)	1985-07-11
DK318683D0 (da)	1983-07-11
DK10684D0 (da)	1984-01-10
DK165545B (da)	1992-12-14

Legal Events

Date	Code	Title	Description
2003-08-19	MKEX	Expiry

Publication	Publication Date	Title
US4374248A (en)	1983-02-15	3,4-Disubstituted-1,2,5-thiadiazole-1-oxide compounds
US4394508A (en)	1983-07-19	Chemical compounds
RU2329043C2 (ru)	2008-07-20	Соединения, воздействующие на глюкокиназу
AU2008299781B2 (en)	2013-11-14	Alkylsulfonyl-substituted thiazolide compounds
CA1190224A (en)	1985-07-09	Derivatives of 1,2-diamino-cyclobutene-3,4-dione as potent histamine h.sub.2-antagonists
EP1716127A2 (de)	2006-11-02	Guanidinverbindungen und ihre verwendung als bindungspartner für 5-ht5-rezeptoren
SK89398A3 (en)	1998-11-04	Phenyl thiazole derivatives with anti herpes virus properties
CA2940954A1 (en)	2010-11-18	Nitazoxanide and tizoxanide for the treatment of rhinovirus and rhabdovirus infections
EP0099121A2 (en)	1984-01-25	Pharmaceutical compositions
US4510309A (en)	1985-04-09	Histamine H2 -antagonists
CA1055505A (en)	1979-05-29	Amidines, isothioureas and guanidines
KR100383495B1 (ko)	2004-05-20	티아디아졸및그의항피코르나바이러스제로서의용도
HU195807B (en)	1988-07-28	Process for producing 5-/azolyl-oxy-phenyl-carbemoyl/-barbituric acid derivatives and anthelmintic compositions containing them
US4380639A (en)	1983-04-19	Substituted 1,2,5-thiadiazole derivatives
US4380638A (en)	1983-04-19	Chemical compounds
HU187877B (en)	1986-02-28	Process for preparing guanidino-heterocyclyl-phenyl-amidines and pharmaceutical compositions containing thereof
HU190669B (en)	1986-10-28	Process for preparing 3,4-disubstituted 1,2,5-thiadiazole-1-oxides and -1,1-dioxides
CA1267412A (en)	1990-04-03	Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine h2-receptor antagonist activity
DK165545B (da)	1992-12-14	Farmaceutisk praeparat til behandling af peptisk ulcus paa enhedsdosisform
US4191769A (en)	1980-03-04	Isothiourea compounds and pharmacological use
CA1253144A (en)	1989-04-25	Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine h.sub.2-receptor antagonist activity
KR850000759B1 (ko)	1985-05-25	3, 4-이치환-1, 2, 5-티아디아졸 1-옥사이드와 1, 1-디옥 사이드의 제조방법
US4170652A (en)	1979-10-09	Heterocyclic-methylthioalkyl-guanidines
LU84484A1 (fr)	1983-09-08	1-oxydes et 1,1-dioxydes de 1,2,5-thiadiazoles 3,4-disubstitudes