CA1142544A - N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl)-n"-alkynylguanidines, agents inhibiteurs des recepteurs h.sub.2 a l'histamine - Google Patents

N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl)-n"-alkynylguanidines, agents inhibiteurs des recepteurs h.sub.2 a l'histamine

Info

Publication number: CA1142544A
Authority: CA; Canada
Prior art keywords: compound; acid addition; addition salt; methyl; cyano
Prior art date: 1977-06-03
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

CA000363136A

Other languages

English (en)

Inventor

Ronnie R. Crenshaw

George M. Luke

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 Squibb Co

Original Assignee

Bristol Myers Squibb 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.)

1977-06-03

Filing date

1980-10-23

Publication date

1983-03-08

1977-11-07 Priority claimed from US05/848,959 external-priority patent/US4112234A/en

1978-05-25 Priority claimed from CA304,045A external-priority patent/CA1110251A/fr

1980-10-23 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1980-10-23 Priority to CA000363136A priority Critical patent/CA1142544A/fr

1983-03-08 Application granted granted Critical

1983-03-08 Publication of CA1142544A publication Critical patent/CA1142544A/fr

Status Expired legal-status Critical Current

Links

239000003087 receptor blocking agent Substances 0.000 title 1
239000002253 acid Substances 0.000 claims abstract description 50
238000000034 method Methods 0.000 claims abstract description 48
150000003839 salts Chemical class 0.000 claims abstract description 38
230000008569 process Effects 0.000 claims abstract description 27
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 13
125000000304 alkynyl group Chemical group 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims description 71
238000002360 preparation method Methods 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 9
125000000217 alkyl group Chemical group 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
125000003396 thiol group Chemical group [H]S* 0.000 claims description 4
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
239000000126 substance Substances 0.000 claims 9
HFVMEOPYDLEHBR-UHFFFAOYSA-N (2-fluorophenyl)-phenylmethanol Chemical compound C=1C=CC=C(F)C=1C(O)C1=CC=CC=C1 HFVMEOPYDLEHBR-UHFFFAOYSA-N 0.000 claims 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 2
QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 claims 2
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 claims 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims 2
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims 2
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 2
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 2
LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 claims 2
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims 2
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 claims 1
125000006501 nitrophenyl group Chemical group 0.000 claims 1
231100000252 nontoxic Toxicity 0.000 abstract description 20
230000003000 nontoxic effect Effects 0.000 abstract description 20
230000002496 gastric effect Effects 0.000 abstract description 11
239000000543 intermediate Substances 0.000 abstract description 8
241001465754 Metazoa Species 0.000 abstract description 7
239000003485 histamine H2 receptor antagonist Substances 0.000 abstract description 7
230000028327 secretion Effects 0.000 abstract description 7
208000008469 Peptic Ulcer Diseases 0.000 abstract description 6
229940122957 Histamine H2 receptor antagonist Drugs 0.000 abstract description 5
208000011906 peptic ulcer disease Diseases 0.000 abstract description 5
238000004519 manufacturing process Methods 0.000 abstract description 3
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 51
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 32
238000006243 chemical reaction Methods 0.000 description 32
229960004198 guanidine Drugs 0.000 description 28
239000000047 product Substances 0.000 description 27
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 25
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 25
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
-1 4-methyl-5-imidazolyl Chemical group 0.000 description 21
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
229960001340 histamine Drugs 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
229960001380 cimetidine Drugs 0.000 description 15
CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 15
239000000243 solution Substances 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
239000000203 mixture Substances 0.000 description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 11
229910052757 nitrogen Inorganic materials 0.000 description 11
238000010992 reflux Methods 0.000 description 11
210000002837 heart atrium Anatomy 0.000 description 10
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000002904 solvent Substances 0.000 description 9
230000000694 effects Effects 0.000 description 8
241000282472 Canis lupus familiaris Species 0.000 description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 6
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 6
241000700159 Rattus Species 0.000 description 6
238000006073 displacement reaction Methods 0.000 description 6
JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 6
239000007787 solid Substances 0.000 description 6
241000700199 Cavia porcellus Species 0.000 description 5
239000007858 starting material Substances 0.000 description 5
238000012360 testing method Methods 0.000 description 5
125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
230000009471 action Effects 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
239000006227 byproduct Substances 0.000 description 4
239000012458 free base Chemical group 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
102000003710 Histamine H2 Receptors Human genes 0.000 description 3
108090000050 Histamine H2 Receptors Proteins 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
IULFXBLVJIPESI-UHFFFAOYSA-N bis(methylsulfanyl)methylidenecyanamide Chemical compound CSC(SC)=NC#N IULFXBLVJIPESI-UHFFFAOYSA-N 0.000 description 3
244000309464 bull Species 0.000 description 3
YLBIBZCIFHPPKA-UHFFFAOYSA-N but-2-yn-1-amine Chemical compound CC#CCN YLBIBZCIFHPPKA-UHFFFAOYSA-N 0.000 description 3
231100000673 dose–response relationship Toxicity 0.000 description 3
238000010828 elution Methods 0.000 description 3
210000004211 gastric acid Anatomy 0.000 description 3
239000000499 gel Substances 0.000 description 3
238000001802 infusion Methods 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
238000012986 modification Methods 0.000 description 3
230000004048 modification Effects 0.000 description 3
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
210000001187 pylorus Anatomy 0.000 description 3
102000005962 receptors Human genes 0.000 description 3
108020003175 receptors Proteins 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
210000002784 stomach Anatomy 0.000 description 3
NYNZQNWKBKUAII-KBXCAEBGSA-N (3s)-n-[5-[(2r)-2-(2,5-difluorophenyl)pyrrolidin-1-yl]pyrazolo[1,5-a]pyrimidin-3-yl]-3-hydroxypyrrolidine-1-carboxamide Chemical compound C1[C@@H](O)CCN1C(=O)NC1=C2N=C(N3[C@H](CCC3)C=3C(=CC=C(F)C=3)F)C=CN2N=C1 NYNZQNWKBKUAII-KBXCAEBGSA-N 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
244000166102 Eucalyptus leucoxylon Species 0.000 description 2
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
206010065713 Gastric Fistula Diseases 0.000 description 2
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 2
208000025865 Ulcer Diseases 0.000 description 2
230000001262 anti-secretory effect Effects 0.000 description 2
238000003556 assay Methods 0.000 description 2
230000001746 atrial effect Effects 0.000 description 2
239000002585 base Substances 0.000 description 2
238000010009 beating Methods 0.000 description 2
230000008901 benefit Effects 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000012043 crude product Substances 0.000 description 2
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 2
125000004705 ethylthio group Chemical group C(C)S* 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
230000027119 gastric acid secretion Effects 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
239000012535 impurity Substances 0.000 description 2
239000003112 inhibitor Substances 0.000 description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
230000001404 mediated effect Effects 0.000 description 2
AOQBTOKIEVBYSK-UHFFFAOYSA-N methyl n-cyano-n'-prop-2-ynylcarbamimidothioate Chemical group N#CNC(SC)=NCC#C AOQBTOKIEVBYSK-UHFFFAOYSA-N 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
230000004044 response Effects 0.000 description 2
238000010517 secondary reaction Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
125000003107 substituted aryl group Chemical group 0.000 description 2
125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
210000001519 tissue Anatomy 0.000 description 2
231100000397 ulcer Toxicity 0.000 description 2
QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 1
KTGRHKOEFSJQNS-BDQAORGHSA-N (1s)-1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-3h-2-benzofuran-5-carbonitrile;oxalic acid Chemical compound OC(=O)C(O)=O.C1([C@]2(C3=CC=C(C=C3CO2)C#N)CCCN(C)C)=CC=C(F)C=C1 KTGRHKOEFSJQNS-BDQAORGHSA-N 0.000 description 1
OVBICQMTCPFEBS-SATRDZAXSA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-[bi Chemical compound CC(O)=O.CC(O)=O.C([C@@H](C(=O)N[C@H](CCCCN=C(NCC)NCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN=C(NCC)NCC)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 OVBICQMTCPFEBS-SATRDZAXSA-N 0.000 description 1
OGMADIBCHLQMIP-UHFFFAOYSA-N 2-aminoethanethiol;hydron;chloride Chemical compound Cl.NCCS OGMADIBCHLQMIP-UHFFFAOYSA-N 0.000 description 1
NORYYEBGVCUVJI-UHFFFAOYSA-N 2-prop-2-ynylguanidine Chemical compound NC(=N)NCC#C NORYYEBGVCUVJI-UHFFFAOYSA-N 0.000 description 1
PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 1
FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 1
125000006519 CCH3 Chemical group 0.000 description 1
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 1
241000700198 Cavia Species 0.000 description 1
244000303965 Cyamopsis psoralioides Species 0.000 description 1
241000448280 Elates Species 0.000 description 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 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
101150056637 Hrh2 gene Proteins 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
102100027256 Melanoma-associated antigen H1 Human genes 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
208000007107 Stomach Ulcer Diseases 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
230000009858 acid secretion Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
238000004458 analytical method Methods 0.000 description 1
229940069428 antacid Drugs 0.000 description 1
239000003159 antacid agent Substances 0.000 description 1
239000005557 antagonist Substances 0.000 description 1
229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
229940077388 benzenesulfonate Drugs 0.000 description 1
RIMGDBZXWSGBQN-UHFFFAOYSA-N burimamide Chemical compound CNC(=S)NCCCCC1=CN=C[N]1 RIMGDBZXWSGBQN-UHFFFAOYSA-N 0.000 description 1
XSBPYGDBXQXSCU-UHFFFAOYSA-N but-3-yn-1-amine Chemical compound NCCC#C XSBPYGDBXQXSCU-UHFFFAOYSA-N 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
239000000812 cholinergic antagonist Substances 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
230000002057 chronotropic effect Effects 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
230000008602 contraction Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000001186 cumulative effect Effects 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
ZPMVNZLARAEGHB-UHFFFAOYSA-N cyproheptadine hydrochloride (anhydrous) Chemical compound Cl.C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 ZPMVNZLARAEGHB-UHFFFAOYSA-N 0.000 description 1
229940097265 cysteamine hydrochloride Drugs 0.000 description 1
108010038764 cytoplasmic linker protein 170 Proteins 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
229960001760 dimethyl sulfoxide Drugs 0.000 description 1
SDIXRDNYIMOKSG-UHFFFAOYSA-L disodium methyl arsenate Chemical compound [Na+].[Na+].C[As]([O-])([O-])=O SDIXRDNYIMOKSG-UHFFFAOYSA-L 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
238000011067 equilibration Methods 0.000 description 1
HHFAWKCIHAUFRX-UHFFFAOYSA-N ethoxide Chemical compound CC[O-] HHFAWKCIHAUFRX-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
108700032141 ganirelix Proteins 0.000 description 1
239000007789 gas Substances 0.000 description 1
210000004051 gastric juice Anatomy 0.000 description 1
210000001156 gastric mucosa Anatomy 0.000 description 1
230000005484 gravity Effects 0.000 description 1
239000000938 histamine H1 antagonist Substances 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
125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
238000011534 incubation Methods 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000011835 investigation Methods 0.000 description 1
150000002541 isothioureas Chemical class 0.000 description 1
239000007788 liquid Substances 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
229960003151 mercaptamine Drugs 0.000 description 1
MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
HQFYIDOMCULPIW-UHFFFAOYSA-N n-methylprop-2-yn-1-amine Chemical compound CNCC#C HQFYIDOMCULPIW-UHFFFAOYSA-N 0.000 description 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
230000037361 pathway Effects 0.000 description 1
239000008188 pellet Substances 0.000 description 1
LMDDPGHBJXJGAC-UHFFFAOYSA-N pent-4-yn-1-amine Chemical compound NCCCC#C LMDDPGHBJXJGAC-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
239000012264 purified product Substances 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
229940044551 receptor antagonist Drugs 0.000 description 1
239000002464 receptor antagonist Substances 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
238000000611 regression analysis Methods 0.000 description 1
210000005245 right atrium Anatomy 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
239000010959 steel Substances 0.000 description 1
239000008174 sterile solution Substances 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
239000000725 suspension Substances 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000363136A 1977-06-03 1980-10-23 N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl)-n"-alkynylguanidines, agents inhibiteurs des recepteurs h.sub.2 a l'histamine Expired CA1142544A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000363136A CA1142544A (fr)	1977-06-03	1980-10-23	N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl)-n"-alkynylguanidines, agents inhibiteurs des recepteurs h.sub.2 a l'histamine

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
US80300977A	1977-06-03	1977-06-03
US803,009		1977-06-03
US82679677A	1977-08-22	1977-08-22
US826,796		1977-08-22
US05/848,959 US4112234A (en)	1977-08-22	1977-11-07	Imidazolylmethylthioethyl alkynyl guanidines
US848,959		1977-11-07
CA304,045A CA1110251A (fr)	1977-06-03	1978-05-25	Agents de blocage du recepteur de h.sub.2 des h- cyano-n'- 2-¬(4-methyl-5- imidazolyl)methylthio\|ethyl -n"-alkynylguanidines
CA000363136A CA1142544A (fr)	1977-06-03	1980-10-23	N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl)-n"-alkynylguanidines, agents inhibiteurs des recepteurs h.sub.2 a l'histamine

Publications (1)

Publication Number	Publication Date
CA1142544A true CA1142544A (fr)	1983-03-08

Family

ID=27508117

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000363136A Expired CA1142544A (fr)	1977-06-03	1980-10-23	N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl)-n"-alkynylguanidines, agents inhibiteurs des recepteurs h.sub.2 a l'histamine

Country Status (1)

Country	Link
CA (1)	CA1142544A (fr)

1980
- 1980-10-23 CA CA000363136A patent/CA1142544A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2000-03-08	MKEX	Expiry

Publication	Publication Date	Title
US4639523A (en)	1987-01-27	Aminoalkylphenoxy derivatives
CA1190224A (fr)	1985-07-09	Derives de la 1,2-diamino-cyclobutene-3,4-dione puissant antagoniste de l'histamine h.sub.2
US4112234A (en)	1978-09-05	Imidazolylmethylthioethyl alkynyl guanidines
EP0053407B1 (fr)	1986-12-30	Imidazolylphényl amidines, procédés de préparation, leur utilisation pharmaceutique et intermédiaires pour leur préparation
US4374843A (en)	1983-02-22	2-Guanidino-4-heteroarylthiazoles
US4200578A (en)	1980-04-29	Thiazole derivatives
NO781635L (no)	1978-11-17	Fremgangsmaate til fremstilling av alkylendiaminer
JPH0699405B2 (ja)	1994-12-07	アリールピペラジニル−アルキレンフェニル複素環式化合物
US4157347A (en)	1979-06-05	N-cyano isothioureas
CA1110251A (fr)	1981-10-06	Agents de blocage du recepteur de h.sub.2 des h- cyano-n'- 2-¬(4-methyl-5- imidazolyl)methylthio\|ethyl -n"-alkynylguanidines
HU181408B (en)	1983-07-28	Process for preparing substituted furan derivatives
US4200760A (en)	1980-04-29	Imidazolylalkylthioalkylamino-ethylene derivatives
CA1130306A (fr)	1982-08-24	N-cyano-n'-[2-[(4-methyl-5-imidazolyl) methyl-thio]ethyl]-n"-alkynylguanidines, inhibiteurs des recepteurs h.sub.2 a l'histamine
USRE31588E (en)	1984-05-22	Imidazolylmethylthioethyl alkynyl guanidines
IE53586B1 (en)	1988-12-21	Triazole gastric anti-secretory agents
US4221737A (en)	1980-09-09	1-(Alkynyl)amino-1-(mercaptoalkyl)amino ethylenes
US5322846A (en)	1994-06-21	4-methylthiazole derivatives, their methods of preparation and the pharmaceutical compositions in which they are present
US4452987A (en)	1984-06-05	Haloacetyl imidazoles
FI73665C (fi)	1987-11-09	Foerfarande foer framstaellning av farmakologiskt vaerdefulla 1-(2-cyano-acylamino-fenyloxi)-3- (2-metylbutinyl-2)-2-propanoler.
JP3081359B2 (ja)	2000-08-28	２−アミノ−１−フェニル−１−エタノール誘導体
KR810000632B1 (ko)	1981-06-10	히스타민 h₂수용기 길항제 또는 비독성인 그의 약조제 가능한 산 첨가염의 제조방법
US4510313A (en)	1985-04-09	2-Guanidino-4-heteroarylthiazoles
JPS61280486A (ja)	1986-12-11	Ｎ−フエニル−４−フエニル−１−ピペラジンカルボキシアミジン類
KR800000411B1 (ko)	1980-05-20	퀴나졸린 유도체의 제조방법
PL96042B1 (pl)	1977-11-30	Sposob wytwarzania nowych aminopochodnych azydofenoli