CA1110251A - N-cyano-n'- 2-¬(4-methyl-5- imidazolyl)methylthio|ethyl - n"-alkynylguanidines h.sub.2 receptor blocking agents - Google Patents

N-cyano-n'- 2-¬(4-methyl-5- imidazolyl)methylthio|ethyl - n"-alkynylguanidines h.sub.2 receptor blocking agents

Info

Publication number: CA1110251A
Authority: CA; Canada
Prior art keywords: compound; formula; acid addition; addition salt; inclusive
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

CA304,045A

Other languages

English (en)

French (fr)

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

1978-05-25

Publication date

1981-10-06

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

1978-05-25 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

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

1980-10-23 Priority to CA363,135A priority patent/CA1130306A/en

1981-10-06 Application granted granted Critical

1981-10-06 Publication of CA1110251A publication Critical patent/CA1110251A/en

Status Expired legal-status Critical Current

Links

-1 4-methyl-5- imidazolyl Chemical group 0.000 title claims description 38
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 title description 25
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 title description 18
239000003087 receptor blocking agent Substances 0.000 title 1
238000000034 method Methods 0.000 claims abstract description 86
239000002253 acid Substances 0.000 claims abstract description 68
150000003839 salts Chemical class 0.000 claims abstract description 62
230000008569 process Effects 0.000 claims abstract description 60
231100000252 nontoxic Toxicity 0.000 claims abstract description 32
230000003000 nontoxic effect Effects 0.000 claims abstract description 32
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
125000000304 alkynyl group Chemical group 0.000 claims abstract description 15
150000001875 compounds Chemical class 0.000 claims description 100
238000007792 addition Methods 0.000 claims description 58
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 45
125000000217 alkyl group Chemical group 0.000 claims description 13
238000002360 preparation method Methods 0.000 claims description 13
239000002904 solvent Substances 0.000 claims description 12
125000003118 aryl group Chemical group 0.000 claims description 8
239000012458 free base Chemical group 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
229910052739 hydrogen Inorganic materials 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 6
125000001424 substituent group Chemical group 0.000 claims description 6
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 5
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 4
239000003960 organic solvent Substances 0.000 claims description 4
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 3
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
239000002585 base Substances 0.000 claims description 3
125000001153 fluoro group Chemical group F* 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
239000000126 substance Substances 0.000 claims 18
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 4
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 4
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims 4
QISOBCMNUJQOJU-UHFFFAOYSA-N 4-bromo-1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1NN=CC=1Br QISOBCMNUJQOJU-UHFFFAOYSA-N 0.000 claims 4
PXRKCOCTEMYUEG-UHFFFAOYSA-N 5-aminoisoindole-1,3-dione Chemical compound NC1=CC=C2C(=O)NC(=O)C2=C1 PXRKCOCTEMYUEG-UHFFFAOYSA-N 0.000 claims 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 4
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims 4
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 4
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 4
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims 4
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 claims 4
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 4
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 4
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 4
229910004279 O3SF Inorganic materials 0.000 claims 2
125000005843 halogen group Chemical group 0.000 claims 2
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NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 abstract description 38
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SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 27
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239000000203 mixture Substances 0.000 description 15
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JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 12
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RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
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IULFXBLVJIPESI-UHFFFAOYSA-N bis(methylsulfanyl)methylidenecyanamide Chemical compound CSC(SC)=NC#N IULFXBLVJIPESI-UHFFFAOYSA-N 0.000 description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 description 6
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YLBIBZCIFHPPKA-UHFFFAOYSA-N but-2-yn-1-amine Chemical compound CC#CCN YLBIBZCIFHPPKA-UHFFFAOYSA-N 0.000 description 3
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230000003042 antagnostic effect Effects 0.000 description 1
230000001262 anti-secretory effect Effects 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
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 1
238000011097 chromatography purification Methods 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
229940097265 cysteamine hydrochloride Drugs 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
229960001760 dimethyl sulfoxide Drugs 0.000 description 1
229940079593 drug Drugs 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
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 1
238000011156 evaluation Methods 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
230000003890 fistula Effects 0.000 description 1
239000000727 fraction Substances 0.000 description 1
108700032141 ganirelix Proteins 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
238000011534 incubation Methods 0.000 description 1
238000001802 infusion 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
150000002500 ions Chemical class 0.000 description 1
150000002541 isothioureas Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
239000006194 liquid suspension Substances 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
229960003151 mercaptamine Drugs 0.000 description 1
WSUNDBVVUCLXTG-UHFFFAOYSA-N methyl n-cyano-n'-[2-[(5-methyl-1h-imidazol-4-yl)methylsulfanyl]ethyl]carbamimidothioate Chemical compound N#CNC(SC)=NCCSCC=1NC=NC=1C WSUNDBVVUCLXTG-UHFFFAOYSA-N 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
235000019796 monopotassium phosphate Nutrition 0.000 description 1
210000003205 muscle Anatomy 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
GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
239000000843 powder Substances 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000012264 purified product Substances 0.000 description 1
150000003254 radicals Chemical class 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
230000000284 resting effect Effects 0.000 description 1
210000005245 right atrium Anatomy 0.000 description 1
239000000377 silicon dioxide Substances 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
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
238000001228 spectrum Methods 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
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 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
231100000397 ulcer Toxicity 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

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/43—Y being a hetero atom
- C07C323/44—X or Y being nitrogen atoms
- 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
- 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
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth 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)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA304,045A 1977-06-03 1978-05-25 N-cyano-n'- 2-¬(4-methyl-5- imidazolyl)methylthio|ethyl - n"-alkynylguanidines h.sub.2 receptor blocking agents Expired CA1110251A (en)

Priority Applications (2)

Application Number	Priority Date	Filing Date	Title
CA000363136A CA1142544A (en)	1977-06-03	1980-10-23	N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl) - n"-alkynylguanidines h.sub.2 receptor blocking agents
CA363,135A CA1130306A (en)	1977-06-03	1980-10-23	N-cyano-n'-[2-[(4-methyl-5-imidazolyl) methylthio]ethyl]- n"-alkynylguanidines h.sub.2 receptor blocking agents

Applications Claiming Priority (6)

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

Publications (1)

Publication Number	Publication Date
CA1110251A true CA1110251A (en)	1981-10-06

Family

ID=27419995

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA304,045A Expired CA1110251A (en)	1977-06-03	1978-05-25	N-cyano-n'- 2-¬(4-methyl-5- imidazolyl)methylthio\|ethyl - n"-alkynylguanidines h.sub.2 receptor blocking agents

Country Status (26)

Country	Link
JP (1)	JPS543067A (de)
AR (2)	AR222797A1 (de)
CA (1)	CA1110251A (de)
CH (2)	CH641167A5 (de)
CY (3)	CY1231A (de)
DD (1)	DD140038A5 (de)
DE (1)	DE2824066A1 (de)
DK (1)	DK243178A (de)
ES (3)	ES470474A1 (de)
FI (1)	FI69069C (de)
FR (2)	FR2401143A1 (de)
GB (3)	GB1598628A (de)
GR (1)	GR73860B (de)
HK (3)	HK38284A (de)
HU (1)	HU186766B (de)
IE (1)	IE47543B1 (de)
IL (1)	IL54819A (de)
KE (1)	KE3373A (de)
LU (1)	LU79725A1 (de)
MY (3)	MY8500451A (de)
NL (1)	NL7805935A (de)
NO (3)	NO152214C (de)
NZ (1)	NZ187376A (de)
SE (3)	SE443784B (de)
SG (1)	SG8584G (de)
YU (4)	YU129778A (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS568352A (en) *	1979-07-03	1981-01-28	Shionogi & Co Ltd	Aminoalkylvenzene derivative
US4339439A (en) *	1981-01-19	1982-07-13	Bristol-Myers Company	Pharmaceutical methods and compositions
JPS6018010U (ja) *	1983-07-18	1985-02-07	日産自動車株式会社	車両用空気調和装置の温度調整機構
JPS60113211U (ja) *	1984-01-06	1985-07-31	松下電器産業株式会社	自動車用空気調和装置
ES2007948A6 (es) *	1988-07-06	1989-07-01	Vinas Lab	Procedimiento para la obtencion de derivados propargilguanidicos.

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4024271A (en) *	1971-03-09	1977-05-17	Smith Kline & French Laboratories Limited	Pharmacologically active guanidine compounds
GB1338169A (en) *	1971-03-09	1973-11-21	Smith Kline French Lab	Ureas thioureas and guanidines
GB1397436A (en) *	1972-09-05	1975-06-11	Smith Kline French Lab	Heterocyclic n-cyanoguinidines
GB1531221A (en) *	1974-09-02	1978-11-08	Smith Kline French Lab	Process for preparing guanidine derivatives
GB1531231A (en) *	1974-09-02	1978-11-08	Smith Kline French Lab	Process for the production of cyanoguanidine derivatives
GB1533380A (en) *	1974-09-02	1978-11-22	Smith Kline French Lab	Process for the preparation of heterocyclic substituted thioureas and h-cyanoguanidines

1978
- 1978-05-25 NZ NZ187376A patent/NZ187376A/xx unknown
- 1978-05-25 CA CA304,045A patent/CA1110251A/en not_active Expired
- 1978-05-26 CY CY1231A patent/CY1231A/en unknown
- 1978-05-26 GB GB23611/78A patent/GB1598628A/en not_active Expired
- 1978-05-26 CY CY1229A patent/CY1229A/en unknown
- 1978-05-26 GB GB18923/80A patent/GB1598630A/en not_active Expired
- 1978-05-26 GB GB27637/79A patent/GB1598629A/en not_active Expired
- 1978-05-26 CY CY1230A patent/CY1230A/en unknown
- 1978-05-29 GR GR56374A patent/GR73860B/el unknown
- 1978-05-29 LU LU79725A patent/LU79725A1/xx unknown
- 1978-05-31 IL IL54819A patent/IL54819A/xx unknown
- 1978-05-31 DK DK243178A patent/DK243178A/da not_active Application Discontinuation
- 1978-05-31 YU YU01297/78A patent/YU129778A/xx unknown
- 1978-05-31 NL NL7805935A patent/NL7805935A/xx not_active Application Discontinuation
- 1978-05-31 AR AR272401A patent/AR222797A1/es active
- 1978-05-31 FI FI781737A patent/FI69069C/fi not_active IP Right Cessation
- 1978-06-01 DE DE19782824066 patent/DE2824066A1/de not_active Withdrawn
- 1978-06-02 IE IE1112/78A patent/IE47543B1/en unknown
- 1978-06-02 ES ES470474A patent/ES470474A1/es not_active Expired
- 1978-06-02 HU HU811135A patent/HU186766B/hu unknown
- 1978-06-02 JP JP6590078A patent/JPS543067A/ja active Granted
- 1978-06-02 NO NO781928A patent/NO152214C/no unknown
- 1978-06-02 FR FR7816601A patent/FR2401143A1/fr active Granted
- 1978-06-02 CH CH609278A patent/CH641167A5/de not_active IP Right Cessation
- 1978-06-02 SE SE7806525A patent/SE443784B/sv unknown
- 1978-06-05 DD DD78205794A patent/DD140038A5/de unknown
1979
- 1979-03-01 ES ES478202A patent/ES478202A1/es not_active Expired
- 1979-03-01 ES ES478203A patent/ES478203A1/es not_active Expired
- 1979-03-05 YU YU530/79A patent/YU41620B/xx unknown
- 1979-05-16 NO NO791637A patent/NO791637L/no unknown
- 1979-10-26 AR AR278645A patent/AR222503A1/es active
- 1979-11-23 FR FR7928943A patent/FR2436138A1/fr active Granted
1982
- 1982-09-27 YU YU2155/82A patent/YU40625B/xx unknown
- 1982-09-27 YU YU2154/82A patent/YU40624B/xx unknown
1983
- 1983-09-12 NO NO833255A patent/NO151824C/no unknown
- 1983-10-07 CH CH549283A patent/CH644591A5/de not_active IP Right Cessation
1984
- 1984-01-30 SG SG85/84A patent/SG8584G/en unknown
- 1984-02-10 KE KE3373A patent/KE3373A/xx unknown
- 1984-03-16 SE SE8401492A patent/SE8401492D0/xx not_active Application Discontinuation
- 1984-03-16 SE SE8401491A patent/SE8401491L/xx not_active Application Discontinuation
- 1984-05-03 HK HK382/84A patent/HK38284A/xx unknown
- 1984-05-03 HK HK380/84A patent/HK38084A/xx unknown
- 1984-05-03 HK HK381/84A patent/HK38184A/xx unknown
1985
- 1985-12-30 MY MY451/85A patent/MY8500451A/xx unknown
- 1985-12-30 MY MY452/85A patent/MY8500452A/xx unknown
- 1985-12-30 MY MY453/85A patent/MY8500453A/xx unknown

Also Published As

Publication number	Publication date
JPS543067A (en)	1979-01-11
HK38284A (en)	1984-05-11
SE8401492L (sv)	1984-03-16
DE2824066A1 (de)	1978-12-14
YU215582A (en)	1983-02-28
IL54819A (en)	1983-03-31
MY8500452A (en)	1985-12-31
FR2436138B1 (de)	1982-12-03
NO151824B (no)	1985-03-04
AR222503A1 (es)	1981-05-29
CY1231A (en)	1984-06-29
SG8584G (en)	1985-02-08
HU186766B (en)	1985-09-30
YU41620B (en)	1987-12-31
YU53079A (en)	1983-09-30
YU40625B (en)	1986-02-28
MY8500453A (en)	1985-12-31
FI69069C (fi)	1985-12-10
GR73860B (de)	1984-05-08
YU129778A (en)	1983-02-28
GB1598628A (en)	1981-09-23
SE8401492D0 (sv)	1984-03-16
FI69069B (fi)	1985-08-30
IE781112L (en)	1978-12-03
FI781737A7 (fi)	1978-12-04
ES478203A1 (es)	1979-06-01
NO833255L (no)	1978-12-05
CY1230A (en)	1984-06-29
CH644591A5 (en)	1984-08-15
FR2401143B1 (de)	1981-12-11
FR2436138A1 (fr)	1980-04-11
FR2401143A1 (fr)	1979-03-23
KE3373A (en)	1984-03-23
GB1598629A (en)	1981-09-23
SE8401491D0 (sv)	1984-03-16
YU40624B (en)	1986-02-28
YU215482A (en)	1983-02-28
ES470474A1 (es)	1979-09-01
NO152214B (no)	1985-05-13
HK38084A (en)	1984-05-11
SE8401491L (sv)	1984-03-16
NO791637L (no)	1978-12-05
NO152214C (no)	1985-08-28
AR222797A1 (es)	1981-06-30
GB1598630A (en)	1981-09-23
NZ187376A (en)	1981-05-29
IL54819A0 (en)	1978-07-31
SE443784B (sv)	1986-03-10
JPS5639313B2 (de)	1981-09-11
CH641167A5 (en)	1984-02-15
HK38184A (en)	1984-05-11
NO781928L (no)	1978-12-05
LU79725A1 (fr)	1979-02-02
SE7806525L (sv)	1978-12-04
NL7805935A (nl)	1978-12-05
IE47543B1 (en)	1984-04-18
CY1229A (en)	1984-06-29
MY8500451A (en)	1985-12-31
DK243178A (da)	1978-12-04
NO151824C (no)	1985-06-12
DD140038A5 (de)	1980-02-06
ES478202A1 (es)	1979-06-01

Publication	Publication Date	Title
CA1190224A (en)	1985-07-09	Derivatives of 1,2-diamino-cyclobutene-3,4-dione as potent histamine h.sub.2-antagonists
US4112234A (en)	1978-09-05	Imidazolylmethylthioethyl alkynyl guanidines
EP0053407B1 (de)	1986-12-30	Imidazolylphenylamidine, Verfahren zur Herstellung, ihre pharmazeutische Anwendung und Zwischenprodukte für ihre Herstellung
US4200578A (en)	1980-04-29	Thiazole derivatives
CA1110251A (en)	1981-10-06	N-cyano-n'- 2-¬(4-methyl-5- imidazolyl)methylthio\|ethyl - n"-alkynylguanidines h.sub.2 receptor blocking agents
US4157347A (en)	1979-06-05	N-cyano isothioureas
US4203909A (en)	1980-05-20	Furan compounds
US4250316A (en)	1981-02-10	Pyridyl guanidine anti-ulcer agents
US3449355A (en)	1969-06-10	2-((3,4-dihalophenoxy)methyl)-2-imidazoline
US4289876A (en)	1981-09-15	Antisecretory agents
US4157340A (en)	1979-06-05	N,N'-[Bis(N-cyanoguanyl)]cystamine derivatives
US3449357A (en)	1969-06-10	2-((2,6-substituted)phenoxymethyl)-2-imidazolines
US4200760A (en)	1980-04-29	Imidazolylalkylthioalkylamino-ethylene derivatives
IL45995A (en)	1977-06-30	4-pyridylthiazole-2-carboxamides and acetamides their preparation and pharmaceutical compositions containing them
USRE31588E (en)	1984-05-22	Imidazolylmethylthioethyl alkynyl guanidines
CA1142544A (en)	1983-03-08	N-cyano-n'-(2-[(4-methyl-5-imidazolyl) methylthio]ethyl) - n"-alkynylguanidines h.sub.2 receptor blocking agents
CA1130306A (en)	1982-08-24	N-cyano-n'-[2-[(4-methyl-5-imidazolyl) methylthio]ethyl]- n"-alkynylguanidines h.sub.2 receptor blocking agents
US4221737A (en)	1980-09-09	1-(Alkynyl)amino-1-(mercaptoalkyl)amino ethylenes
US4282363A (en)	1981-08-04	1-Nitro-2-(2-alkynylamino)-2-[(2-pyridylmethylthio)-ethylamino]ethylene derivatives
KR800000411B1 (ko)	1980-05-20	퀴나졸린 유도체의 제조방법
KR810000632B1 (ko)	1981-06-10	히스타민 h₂수용기 길항제 또는 비독성인 그의 약조제 가능한 산 첨가염의 제조방법
GB2038798A (en)	1980-07-30	(Hydroxymethyl imidazolyl) methylthioethyl guanidine derivatives

Legal Events

Date	Code	Title	Description
1998-10-06	MKEX	Expiry