CA1253144A - Derives de substitution de 3,4-diamino-1,2,5- thiadiazoles, inhibiteurs des recepteurs h.sub.2 a l'histamine - Google Patents

Derives de substitution de 3,4-diamino-1,2,5- thiadiazoles, inhibiteurs des recepteurs h.sub.2 a l'histamine

Info

Publication number: CA1253144A
Authority: CA; Canada
Prior art keywords: compound; formula; solvate; hydrate; methyl
Prior art date: 1982-03-29
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

CA000501205A

Other languages

English (en)

Inventor

Ronnie R. Crenshaw

Aldo A. Algieri

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.)

1982-03-29

Filing date

1986-02-05

Publication date

1989-04-25

1983-03-16 Priority claimed from US06/473,791 external-priority patent/US4528377A/en

1986-02-05 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1986-02-05 Priority to CA000501205A priority Critical patent/CA1253144A/fr

1989-04-25 Application granted granted Critical

1989-04-25 Publication of CA1253144A publication Critical patent/CA1253144A/fr

Status Expired legal-status Critical Current

Links

NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 title description 24
229960001340 histamine Drugs 0.000 title description 12
230000000694 effects Effects 0.000 title description 7
229940044551 receptor antagonist Drugs 0.000 title description 2
239000002464 receptor antagonist Substances 0.000 title description 2
IPLXKLUYTPGIPL-UHFFFAOYSA-N 1,2,5-thiadiazole-3,4-diamine Chemical class NC1=NSN=C1N IPLXKLUYTPGIPL-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 158
RDJGIQPSSNMJPF-UHFFFAOYSA-N ethanediimidamide Chemical class NC(=N)C(N)=N RDJGIQPSSNMJPF-UHFFFAOYSA-N 0.000 claims abstract description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 72
239000001257 hydrogen Substances 0.000 claims description 72
239000012453 solvate Substances 0.000 claims description 68
150000003839 salts Chemical class 0.000 claims description 67
238000000034 method Methods 0.000 claims description 65
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
-1 methylenedioxy Chemical group 0.000 claims description 51
125000000217 alkyl group Chemical group 0.000 claims description 45
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 29
229910052757 nitrogen Inorganic materials 0.000 claims description 29
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 28
125000003545 alkoxy group Chemical group 0.000 claims description 26
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 25
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 19
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 18
239000000126 substance Substances 0.000 claims description 16
150000002431 hydrogen Chemical group 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 13
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 12
229910052760 oxygen Inorganic materials 0.000 claims description 12
239000001301 oxygen Substances 0.000 claims description 12
125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
229910052717 sulfur Inorganic materials 0.000 claims description 9
239000011593 sulfur Substances 0.000 claims description 9
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
125000004432 carbon atom Chemical group C* 0.000 claims description 7
229910052500 inorganic mineral Inorganic materials 0.000 claims description 7
239000011707 mineral Substances 0.000 claims description 7
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 7
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 5
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 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
239000012442 inert solvent Substances 0.000 claims 6
238000004519 manufacturing process Methods 0.000 claims 6
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 3
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 3
PAYQAJAIDCYYNG-UHFFFAOYSA-N 2-N'-[3-(2-methyl-3-piperidin-1-ylphenoxy)propyl]ethanediimidamide Chemical compound N1(CCCCC1)C=1C(=C(OCCCNC(C(N)=N)=N)C=CC=1)C PAYQAJAIDCYYNG-UHFFFAOYSA-N 0.000 claims 2
HEEMXYTYHZOZBH-UHFFFAOYSA-N 2-N'-[2-[(2-methyl-5-piperidin-1-ylthiophen-3-yl)methylsulfanyl]ethyl]ethanediimidamide Chemical compound N1(CCCCC1)C1=CC(=C(S1)C)CSCCNC(C(N)=N)=N HEEMXYTYHZOZBH-UHFFFAOYSA-N 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 11
229940122957 Histamine H2 receptor antagonist Drugs 0.000 abstract description 5
239000003485 histamine H2 receptor antagonist Substances 0.000 abstract description 5
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 46
239000000047 product Substances 0.000 description 40
125000006308 propyl amino group Chemical group 0.000 description 38
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
235000002639 sodium chloride Nutrition 0.000 description 24
239000000243 solution Substances 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
229910001868 water Inorganic materials 0.000 description 19
239000000203 mixture Substances 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
238000006243 chemical reaction Methods 0.000 description 16
239000000725 suspension Substances 0.000 description 15
238000003756 stirring Methods 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 10
239000000543 intermediate Substances 0.000 description 10
231100000252 nontoxic Toxicity 0.000 description 10
230000003000 nontoxic effect Effects 0.000 description 10
QYIWBOWEQBEAGP-UHFFFAOYSA-N 2-(1,3-dioxoisoindol-2-yl)sulfanylisoindole-1,3-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1SN1C(=O)C2=CC=CC=C2C1=O QYIWBOWEQBEAGP-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 9
239000000523 sample Substances 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
230000002496 gastric effect Effects 0.000 description 8
210000002837 heart atrium Anatomy 0.000 description 8
238000012360 testing method Methods 0.000 description 8
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 7
229960001380 cimetidine Drugs 0.000 description 7
CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 7
PXJJSXABGXMUSU-UHFFFAOYSA-N disulfur dichloride Chemical compound ClSSCl PXJJSXABGXMUSU-UHFFFAOYSA-N 0.000 description 7
230000028327 secretion Effects 0.000 description 7
UDGKZGLPXCRRAM-UHFFFAOYSA-N 1,2,5-thiadiazole Chemical compound C=1C=NSN=1 UDGKZGLPXCRRAM-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
241000700159 Rattus Species 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 6
KXOFUUASPAGCPE-UHFFFAOYSA-N ethanediimidamide trihydrochloride Chemical compound Cl.Cl.Cl.C(C(N)=N)(N)=N KXOFUUASPAGCPE-UHFFFAOYSA-N 0.000 description 6
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
239000011541 reaction mixture Substances 0.000 description 6
239000000377 silicon dioxide Substances 0.000 description 6
241001024304 Mino Species 0.000 description 5
229910052943 magnesium sulfate Inorganic materials 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 5
241000700199 Cavia porcellus Species 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
239000012043 crude product Substances 0.000 description 4
231100000673 dose–response relationship Toxicity 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
150000002500 ions Chemical class 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
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 4
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 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
125000001424 substituent group Chemical group 0.000 description 4
229910017974 NH40H Inorganic materials 0.000 description 3
244000018764 Nyssa sylvatica Species 0.000 description 3
235000003339 Nyssa sylvatica Nutrition 0.000 description 3
WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000003814 drug Substances 0.000 description 3
239000003480 eluent Substances 0.000 description 3
UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 3
239000000284 extract Substances 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
239000001530 fumaric acid Substances 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
230000035484 reaction time Effects 0.000 description 3
238000006798 ring closing metathesis reaction Methods 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
239000007858 starting material Substances 0.000 description 3
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 3
WEKYWIBCHONDBC-UHFFFAOYSA-N 3-[6-(piperidin-1-ylmethyl)pyridin-2-yl]oxypropan-1-amine Chemical compound NCCCOC1=CC=CC(CN2CCCCC2)=N1 WEKYWIBCHONDBC-UHFFFAOYSA-N 0.000 description 2
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
208000008469 Peptic Ulcer Diseases 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
238000003556 assay Methods 0.000 description 2
230000001746 atrial effect Effects 0.000 description 2
238000010009 beating Methods 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000001035 drying Methods 0.000 description 2
238000011156 evaluation Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000012458 free base Substances 0.000 description 2
230000027119 gastric acid secretion Effects 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
150000004677 hydrates Chemical class 0.000 description 2
238000002513 implantation Methods 0.000 description 2
239000004615 ingredient Substances 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
NIQQIJXGUZVEBB-UHFFFAOYSA-N methanol;propan-2-one Chemical compound OC.CC(C)=O NIQQIJXGUZVEBB-UHFFFAOYSA-N 0.000 description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 2
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
238000000746 purification Methods 0.000 description 2
102000005962 receptors Human genes 0.000 description 2
108020003175 receptors Proteins 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
210000002784 stomach Anatomy 0.000 description 2
FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
238000002627 tracheal intubation Methods 0.000 description 2
YGKOYVNJPRSSRX-UHFFFAOYSA-M (4-dodecylphenyl)methyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCCCCCCC1=CC=C(C[N+](C)(C)C)C=C1 YGKOYVNJPRSSRX-UHFFFAOYSA-M 0.000 description 1
GXZDYRYYNXYPMQ-UHFFFAOYSA-N 2-chloro-6-methylpyridine Chemical compound CC1=CC=CC(Cl)=N1 GXZDYRYYNXYPMQ-UHFFFAOYSA-N 0.000 description 1
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
SXAKEWROCCBLGU-UHFFFAOYSA-N 3-N-[3-[3-[(dimethylamino)methyl]phenyl]sulfanylpropyl]-1,2,5-thiadiazole-3,4-diamine Chemical compound NC1=NSN=C1NCCCSC1=CC(=CC=C1)CN(C)C SXAKEWROCCBLGU-UHFFFAOYSA-N 0.000 description 1
AAEOEVRPMYKMKS-UHFFFAOYSA-N 3-[4-(piperidin-1-ylmethyl)pyridin-2-yl]oxypropan-1-amine Chemical compound C1=NC(OCCCN)=CC(CN2CCCCC2)=C1 AAEOEVRPMYKMKS-UHFFFAOYSA-N 0.000 description 1
QCHHKUYJOJEKBO-UHFFFAOYSA-N 3-[6-[(dimethylamino)methyl]pyridin-2-yl]oxypropan-1-amine Chemical compound CN(C)CC1=CC=CC(OCCCN)=N1 QCHHKUYJOJEKBO-UHFFFAOYSA-N 0.000 description 1
WSGYTJNNHPZFKR-UHFFFAOYSA-N 3-hydroxypropanenitrile Chemical compound OCCC#N WSGYTJNNHPZFKR-UHFFFAOYSA-N 0.000 description 1
FIGKQXOGRKFRGS-UHFFFAOYSA-N 3-n-[3-[6-(piperidin-1-ylmethyl)pyridin-2-yl]oxypropyl]-1,2,5-thiadiazole-3,4-diamine Chemical compound NC1=NSN=C1NCCCOC1=CC=CC(CN2CCCCC2)=N1 FIGKQXOGRKFRGS-UHFFFAOYSA-N 0.000 description 1
KESHAMUNPHJULK-UHFFFAOYSA-N 4-methoxy-1,2,5-thiadiazol-3-amine Chemical compound COC1=NSN=C1N KESHAMUNPHJULK-UHFFFAOYSA-N 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
241000700198 Cavia Species 0.000 description 1
102100032392 Circadian-associated transcriptional repressor Human genes 0.000 description 1
101710130150 Circadian-associated transcriptional repressor Proteins 0.000 description 1
241000518994 Conta Species 0.000 description 1
101000837192 Drosophila melanogaster Teneurin-m Proteins 0.000 description 1
206010016717 Fistula Diseases 0.000 description 1
206010065713 Gastric Fistula Diseases 0.000 description 1
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 1
102000003710 Histamine H2 Receptors Human genes 0.000 description 1
108090000050 Histamine H2 Receptors Proteins 0.000 description 1
241000708948 Solva Species 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
229940094070 ambien Drugs 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
230000001262 anti-secretory effect Effects 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
238000010533 azeotropic distillation Methods 0.000 description 1
239000002585 base Substances 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
RIMGDBZXWSGBQN-UHFFFAOYSA-N burimamide Chemical compound CNC(=S)NCCCCC1=CN=C[N]1 RIMGDBZXWSGBQN-UHFFFAOYSA-N 0.000 description 1
208000037516 chromosome inversion disease Diseases 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000008602 contraction Effects 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
NGDNCZPCIZNCQS-UHFFFAOYSA-N ctk3j8699 Chemical compound Cl=S NGDNCZPCIZNCQS-UHFFFAOYSA-N 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
230000000881 depressing effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
238000011067 equilibration Methods 0.000 description 1
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
230000003890 fistula Effects 0.000 description 1
239000006260 foam Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
229960004931 histamine dihydrochloride Drugs 0.000 description 1
PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
125000001145 hydrido group Chemical class *[H] 0.000 description 1
238000011534 incubation Methods 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000004811 liquid chromatography Methods 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
238000013289 male long evans rat Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 1
ZHBQANCZLAYTEH-UHFFFAOYSA-N methyl 2-[8-[(2,6-dimethylmorpholin-4-yl)methyl]-1,3-dimethyl-2,6-dioxopurin-7-yl]acetate Chemical compound N=1C=2N(C)C(=O)N(C)C(=O)C=2N(CC(=O)OC)C=1CN1CC(C)OC(C)C1 ZHBQANCZLAYTEH-UHFFFAOYSA-N 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
HPQIDJKQMFOBKA-UHFFFAOYSA-N n-[3-[3-(piperidin-1-ylmethyl)phenoxy]propyl]-4-prop-2-ynyl-1,2,5-thiadiazol-3-amine Chemical compound C#CCC1=NSN=C1NCCCOC1=CC=CC(CN2CCCCC2)=C1 HPQIDJKQMFOBKA-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
230000001575 pathological effect Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
208000011906 peptic ulcer disease Diseases 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000012264 purified product Substances 0.000 description 1
239000012521 purified sample Substances 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000006215 rectal suppository Substances 0.000 description 1
229940100618 rectal suppository Drugs 0.000 description 1
238000011160 research Methods 0.000 description 1
239000011369 resultant mixture Substances 0.000 description 1
210000005245 right atrium Anatomy 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000002904 solvent Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
238000012956 testing procedure Methods 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
238000004448 titration Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1
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 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CA000501205A 1982-03-29 1986-02-05 Derives de substitution de 3,4-diamino-1,2,5- thiadiazoles, inhibiteurs des recepteurs h.sub.2 a l'histamine Expired CA1253144A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000501205A CA1253144A (fr)	1982-03-29	1986-02-05	Derives de substitution de 3,4-diamino-1,2,5- thiadiazoles, inhibiteurs des recepteurs h.sub.2 a l'histamine

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
US36320782A	1982-03-29	1982-03-29
US363,207		1982-03-29
US06/473,791 US4528377A (en)	1982-03-29	1983-03-16	Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine H2 -receptor antagonist activity
CA000424612A CA1228067A (fr)	1982-03-29	1983-03-28	Derives de substitution de 3,4-diamino-1,2,5- thiadiazoles, antagonistes pour les recepteurs h.sub.2 a l'histamine
CA000501205A CA1253144A (fr)	1982-03-29	1986-02-05	Derives de substitution de 3,4-diamino-1,2,5- thiadiazoles, inhibiteurs des recepteurs h.sub.2 a l'histamine
US473,791		1990-02-02

Publications (1)

Publication Number	Publication Date
CA1253144A true CA1253144A (fr)	1989-04-25

Family

ID=27167334

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000501205A Expired CA1253144A (fr)	1982-03-29	1986-02-05	Derives de substitution de 3,4-diamino-1,2,5- thiadiazoles, inhibiteurs des recepteurs h.sub.2 a l'histamine

Country Status (1)

Country	Link
CA (1)	CA1253144A (fr)

1986
- 1986-02-05 CA CA000501205A patent/CA1253144A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2006-04-25	MKEX	Expiry

Publication	Publication Date	Title
CA1190224A (fr)	1985-07-09	Derives de la 1,2-diamino-cyclobutene-3,4-dione puissant antagoniste de l'histamine h.sub.2
CA1263115A (fr)	1989-11-21	Derives de 1,2,5-thiadiazole-1-oxydes et -1,1- dioxydes, inhibiteurs des recepteurs h2 a l'histamine
US4440933A (en)	1984-04-03	Process for preparing 1,2,5-thiadiazoles
IE49320B1 (en)	1985-09-18	N-alkynyl-n'((optionally substituted thiazolyl)methylthio)alkyl-derivatives of n"-cyanoguanidine and of 1,1-diamino-2-substituted ethylene
US4528375A (en)	1985-07-09	Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine H2 -receptor antagonist activity
US4526973A (en)	1985-07-02	Chemical compounds
US4528377A (en)	1985-07-09	Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine H2 -receptor antagonist activity
US4528378A (en)	1985-07-09	Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine H2 -receptor antagonist activity
US4600779A (en)	1986-07-15	Substituted 3,4-diamino-1,2,5-thiadiazoles having histamine H2 -receptor antagonist activity
US4588826A (en)	1986-05-13	Ethanediimidamide intermediates
US4395553A (en)	1983-07-26	Chemical compounds
US4578471A (en)	1986-03-25	Substituted amino alkyl pyridyl ethanediimidamides
US4503051A (en)	1985-03-05	Substituted 3-cyclobutene-1,2-diones, pharmaceutical compositions thereof and methods of use
GB2117769A (en)	1983-10-19	Substituted diamino-thiadiazoles
US4539316A (en)	1985-09-03	Pyridine derivatives of 1,2-diaminocyclobutene-3,4-diones
US4595758A (en)	1986-06-17	Ethanediimidamide intermediates
US4517366A (en)	1985-05-14	Intermediates for preparing 3,4-diamino-1,2,5-thiadiazoles
US4507485A (en)	1985-03-26	3,4-Disubstituted-1,2,5-oxadiazoles having histamine H2 -receptor antagonist activity
FI69069C (fi)	1985-12-10	Foerfarande foer framstaellning av terapeutiskt anvaendbara n-yan-n'-(2-((4-metyl-5-imidazolyl)metyltio)etyl)-n"-alkyny lganidiner
US4546188A (en)	1985-10-08	Substituted 1,2-diaminocyclobutene-3,4-diones
US4788184A (en)	1988-11-29	Substituted 3-cyclobutene-1,2-diones as anti-ulcer agents
KR880002530B1 (ko)	1988-11-28	치환된 에탄디이미드 아미드 및 그의 제조방법
CA1190225A (fr)	1985-07-09	Derives du cyclobutene -3, 4- dione servant d'intermediaire pour des antihistaminiques anti-h.sub.2
KR810000058B1 (ko)	1981-02-04	구아니딘의 헤테로 고리화합물 유도체의 제조방법
GB2161157A (en)	1986-01-08	Thiadiazoles