CY1231A - N-cyano-n'-alkynyl-s-substituted isothioureas - Google Patents

N-cyano-n'-alkynyl-s-substituted isothioureas Download PDF

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Publication number
CY1231A
CY1231A CY1231A CY123178A CY1231A CY 1231 A CY1231 A CY 1231A CY 1231 A CY1231 A CY 1231A CY 123178 A CY123178 A CY 123178A CY 1231 A CY1231 A CY 1231A
Authority
CY
Cyprus
Prior art keywords
cyano
butyn
compound
methyl
alkynyl
Prior art date
Application number
CY1231A
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.)
Filing date
Publication date
Priority claimed from US05/848,959 external-priority patent/US4112234A/en
Application filed by Bristol Myers Co filed Critical Bristol Myers Co
Publication of CY1231A publication Critical patent/CY1231A/en

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04Drugs 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23Thiols, 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
    • C07C323/39Thiols, 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
    • C07C323/43Y being a hetero atom
    • C07C323/44X or Y being nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic 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
    • C07D233/64Heterocyclic 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

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  • 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)

Description

PATENT SPECIFICATION
Oi (21) Application No. 27637/79 (22) Filed 26 May 1978 (62) Divided out of No. 1598628 (31) Convention Application No. 803009 0© (32) Filed 3 June 1977
(31) Convention Application No. 826796
(32) Filed 22 Aug. 1977 ^ (31) Convention Application No. 848959
(32) Filed 7 Nov. 1977 in
(33) United States of America (US)
(44) Complete Specification published 23 Sept. 1981
(51) INT CL3 C07C 157/14
(52) Index at acceptance
C2C 202 20Y 30Y 320 326 373 37Y 746 758 AA RH
(54) N-CYANO-N'-ALKYNYL-S-SUBSTITUTED ISOTHIOUREAS
(71) We, BRISTOL-MYERS COMPANY, a Corporation organised and existing under the laws of the State of Delaware United States of America, of 345 Park Avenue, State of New York, 10022, United States of America, do hereby declare the invention for which we pray that a patent may be granted to us and the 5 method by which it is to be performed to be particularly described in and by the 5
following statement:—
The present invention relates to certain N-cyano-N'-alkynyl-S-substituted isothioureas which are intermediates useful in the preparation of certain N-cyano-N'-{2 - [(4 - methyl - 5 - imidazolyl)methylthio] - ethyl}-N"-alkynylguanidines 10 which are H2 receptor blocking agents, which inhibit gastric acid secretion and 10 which are useful in the treatment of ulcers.
Accordingly, the present invention provides a compound of the formula
NCN
II
R2S—CNH—R1 III
wherein R1 is a straight or branched chain alkynyl group containing from 3 to 9 15 carbon atoms and R2 is C,_9alkyl, aryl, substituted aryl, aralkyl, —CH2CN, 15 —CH,COOH or —CH2COOR' wherein R' is C,_9 lower alkyl.
"In a preferred embodiment, R1 of the compound of formula III is
—CHOCR4
I
ch3
in which R* is hydrogen or methyl; in another preferred embodiment R' is ;20 —<CH2)nC=CR4 20 ;in which n is an integer of from 1 to 6 and R4 is hydrogen or methyl; in another preferred embodiment R1 is ;CH3 ! ;—C—OCR4 ;I ;ch3 ;in which R4 is hydrogen or methyl. ;25 In a more preferred embodiment, R1 is a propargyl, 2-butyn-l-yl, 3-butyn-l-yl, 25 ;2-methyl-3-butyn-2-yl, or 4-pentyn-l-yl group. ;<"> 1 598 629 ;BNSDOCID: <GB 1598629A L> ;1,598,629 ;The compounds of the present invention are intermediates in the preparation of compounds of the formula ;N y^°H3 ;OL ;ncn ;1 ;n ch2sch2ch2nhcnh-r h ;10 ;wherein R1 is a straight or branched chain alkynyl group containing from 3 to 9 carbon atoms, or non-toxic pharmaceutically acceptable acid addition salts thereof. _ . ;The compounds of formula I are described and claimed in our copending patent application No. 23611/7*8. Serial No. 1,598,628.
The compounds of formula I and salts thereof may be prepared by reacting a compound of the formula
10
a i
H
ch.
ch2sch2ch2nh2
ii or an acid addition salt thereof, with a compound of the formula
NCN
II
R2S—CNH—R1
III
wherein R1 and R2 are as above defined, and, if desired, converting the resulting 15 compound of formula I in basic form or an acid addition salt thereof to the corresponding non-toxic pharmaceutically acceptable acid addition salt or free base form.
This process is illustrated by way of example by the following reaction scheme: ch-,
H2sch2CH2NH2 +
ncn
2. n rs-cnhch2c3ch
15
rT
^N-^C
ch.
ncn
H
ch2sch2ch 2nhcnhch 2csch
20 wherein R2 is as above defined
The compounds of the present invention may be prepared by the reaction of an appropriately substituted cyanodithioiminocarbonate with an alkynylamine having from 3 to 9 carbon atoms. The general reaction scheme is given below:—
20
BNSDQCID: <GB 1598629A_I_>
3
5
10
15
20
25
30
35
40
45
50
_3
5
10
15
20
25
30
35
40
45
50
1,598,629
NCN
II
(R2S)2G=NCN+ H2NR'-»R2S—CNHR'+R2SH
The present invention will be further described with reference to the following Examples.
EXAMPLE 1 N-Cyano-N'-propargyl-S-methylisothiourea A solution of dimethyl cyanodithioiminocarbonate (16.00 g, 0.109 mole) and propargylamine (6.03 g, 0.109 mole) in acetonitrile (320 ml) was stirred at reflux for 4 hours, and then at 25°C for 12 hours. Workup gave the title compound (13.58 g, 81%), mp 160—164°C.
EXAMPLE 2 N-(2-Butyn-l-yl)-N'-cyano-S-methylisothiourea A solution of dimethyl cyanodithioiminocarbonate (10.00 g, 0.684 mole) and 2-butyn-l-yl-amine (4.73 g, 0.684 mole) in acetonitrile (200 ml) was stirred at reflux for 2.5 hours. The mixture was cooled, then filtered to yield the title compound, mp 180—183°C.
EXAMPLE 3
N-( 1,1 -Dimethylpropargyl)-N'-cyano-S-methylisothiourea The general procedure of Example 2 is repeated except that the 2-butyn-l-yl-amine utilized therein is replaced by an equimolar amount of 1,1-dimethylpropargylamine, and the title product is thereby produced.
EXAMPLE 4 N-( 1 -Methylpropargyl)-N'-cyano-S-methylisothiourea The general procedure of Example 2 is repeated except that the 2-butyn-l-yl-amine utilized therein is replaced by an equimolar amount of 1-methylpropargylamine, and the title product is thereby produced.
EXAMPLE 5 N-Cyano-N'-propargyl-S-methylisothiourea A solution of dimethyl cyanodithioiminocarbonate (16.00 g, 0.109 mole) and propargylamine (6.03 g, 0.109 mole) in acetonitrile (320 ml) was stirred at reflux for 4 hours, and then at 25 °C for 12 hours. The mixture was cooled and filtered to yield the title compound (13.58 g, 81%), mp 160—164°C.
EXAMPLE 6 N-Cyano-N'-(2-butyn-l-yl-S-methylisothiourea A solution of dimethyl cyanodithioiminocarbonate (10.00 g, 0.0684 mole) and 2-butyn-l-yl-amine (4.73 g, 0.0684 mole) in acetonitrile (200 ml) was stirred at 25°C for 0.5 hour, and then at reflux for 2.5 hours. The mixture was cooled, then filtered to yield the title compound, mp 180—183°C.
EXAMPLE 7 N-Cyano-N'-(3-butyn-1 -yl)-S-methylisothiourea The general procedure of Example 5 is repeated, except that the propargylamine utilized therein is replaced by an equimolar amount of 3-butyn-l-yl-amine, and the title compound is thereby produced.
EXAMPLE 8 N-Cyano-N'-(4-pentyn-1 -yl)-S-methylisothiourea The general procedure of Example 5 is repeated, except that the propargylamine utilzed therein is replaced by an equimolar amount of 4-pentyn-l-yl-amine, and the title compound is thereby produced.
EXAMPLE 9
N-Cyano-N'-(2-methyl-3-butyn-2-yl)-S-methylisothiourea The general procedure of Example 5 is repeated, except that the propargylamine utilized therein is replaced by an equimolar amount of 1,1-dimethylpropargylamine, and the title compound is thereby produced.
1,598,629
EXAMPLE 10 N-Cyano-N'-(3-butyn-2-yl)-S-methylisothiourea The general procedure of Example 5 is repeated, except that the propargylamine utilized therein is replaced an equimolar amount of 1-methyl-5 propargylamine, and the title compound is thereby produced. 5
WHAT WE CLAIM IS:—
1. A compound of the formula
NCN
li
RZS—CNH—R1
wherein R1 is a straight or branched chain alkvnyl group containing from 3 to 9 10 carbon atoms, inclusive, and R2 is C,_9alkyl, aryl, substituted aryl, aralkyl, 10 —CH2CN, —CN,COOH or —CH2COOR' where R' is C,_9alkyl.
2. A compound as claimed in claim 1 in which R1 is
—(ch2)n=cr4
wherein n is an integer of from 1 to 6, inclusive, and R4 is hydrogen or methyl. 15 3. A compound as claimed in claim 1 in which R1 is 15
—CHC=CR4
I
ch3
wherein R4 is hydrogen or methyl.
4. A compound as claimed in claim 1 in which R1 is ch3
I
—C—OCR4
I
ch3
20 wherein R4 is hydrogen or methyl. 20
5. A compound as claimed in claim 1 wherein R1 is a propargyl, 2-butyn-l-yl, 3-butyn-l-yl, 2-methyl-3-butyn-2-yl, or 4-pentyn-I-yI group.
6. A process for preparing a compound as claimed in claim I substantially as hereinbefore described with reference to any one of the Examples.
25 7. A compound as claimed in claim 1 whenever prepared by a process as 25

Claims (1)

  1. claimed in claim 6.
    BOULT, WADE & TENNANT,
    27 Furnival Street,
    London EC4A 1PQ.
    Printed for Her Majesty's Stationery Office, by the Courier Press, Leamington Spa, 1981 Published by The Patent Office, 25 Southampton Buildings, London, WC2A 1AY, from which copies may be obtained.
    BNSDOCID: <GB 1598629A_L>
CY1231A 1977-06-03 1978-05-26 N-cyano-n'-alkynyl-s-substituted isothioureas CY1231A (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US80300977A 1977-06-03 1977-06-03
US82679677A 1977-08-22 1977-08-22
US05/848,959 US4112234A (en) 1977-08-22 1977-11-07 Imidazolylmethylthioethyl alkynyl guanidines

Publications (1)

Publication Number Publication Date
CY1231A true CY1231A (en) 1984-06-29

Family

ID=27419995

Family Applications (3)

Application Number Title Priority Date Filing Date
CY1230A CY1230A (en) 1977-06-03 1978-05-26 N-cyano-n'-alkynyl-n''-(2-mercaptoethyl)-guanidines
CY1229A CY1229A (en) 1977-06-03 1978-05-26 Guanidine derivatives
CY1231A CY1231A (en) 1977-06-03 1978-05-26 N-cyano-n'-alkynyl-s-substituted isothioureas

Family Applications Before (2)

Application Number Title Priority Date Filing Date
CY1230A CY1230A (en) 1977-06-03 1978-05-26 N-cyano-n'-alkynyl-n''-(2-mercaptoethyl)-guanidines
CY1229A CY1229A (en) 1977-06-03 1978-05-26 Guanidine derivatives

Country Status (26)

Country Link
JP (1) JPS543067A (en)
AR (2) AR222797A1 (en)
CA (1) CA1110251A (en)
CH (2) CH641167A5 (en)
CY (3) CY1230A (en)
DD (1) DD140038A5 (en)
DE (1) DE2824066A1 (en)
DK (1) DK243178A (en)
ES (3) ES470474A1 (en)
FI (1) FI69069C (en)
FR (2) FR2401143A1 (en)
GB (3) GB1598628A (en)
GR (1) GR73860B (en)
HK (3) HK38084A (en)
HU (1) HU186766B (en)
IE (1) IE47543B1 (en)
IL (1) IL54819A (en)
KE (1) KE3373A (en)
LU (1) LU79725A1 (en)
MY (3) MY8500453A (en)
NL (1) NL7805935A (en)
NO (3) NO152214C (en)
NZ (1) NZ187376A (en)
SE (3) SE443784B (en)
SG (1) SG8584G (en)
YU (4) YU129778A (en)

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 (en) * 1983-07-18 1985-02-07 日産自動車株式会社 Temperature adjustment mechanism of vehicle air conditioner
JPS60113211U (en) * 1984-01-06 1985-07-31 松下電器産業株式会社 Automotive air conditioner
ES2007948A6 (en) * 1988-07-06 1989-07-01 Vinas Lab Propargylguanidine derivatives and process for the preparation thereof.

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

Also Published As

Publication number Publication date
YU215582A (en) 1983-02-28
YU41620B (en) 1987-12-31
YU53079A (en) 1983-09-30
NO781928L (en) 1978-12-05
HU186766B (en) 1985-09-30
IL54819A0 (en) 1978-07-31
FR2401143A1 (en) 1979-03-23
CA1110251A (en) 1981-10-06
FR2401143B1 (en) 1981-12-11
NO151824C (en) 1985-06-12
SE8401492D0 (en) 1984-03-16
HK38284A (en) 1984-05-11
FR2436138A1 (en) 1980-04-11
ES478202A1 (en) 1979-06-01
GB1598629A (en) 1981-09-23
SE443784B (en) 1986-03-10
FI69069C (en) 1985-12-10
KE3373A (en) 1984-03-23
NO833255L (en) 1978-12-05
DK243178A (en) 1978-12-04
YU40625B (en) 1986-02-28
IE47543B1 (en) 1984-04-18
HK38184A (en) 1984-05-11
SG8584G (en) 1985-02-08
MY8500451A (en) 1985-12-31
DD140038A5 (en) 1980-02-06
AR222503A1 (en) 1981-05-29
NZ187376A (en) 1981-05-29
CY1230A (en) 1984-06-29
FR2436138B1 (en) 1982-12-03
JPS543067A (en) 1979-01-11
CY1229A (en) 1984-06-29
NO791637L (en) 1978-12-05
FI781737A7 (en) 1978-12-04
GR73860B (en) 1984-05-08
CH641167A5 (en) 1984-02-15
CH644591A5 (en) 1984-08-15
MY8500452A (en) 1985-12-31
IE781112L (en) 1978-12-03
YU215482A (en) 1983-02-28
ES470474A1 (en) 1979-09-01
NO152214C (en) 1985-08-28
SE7806525L (en) 1978-12-04
GB1598630A (en) 1981-09-23
NL7805935A (en) 1978-12-05
NO151824B (en) 1985-03-04
SE8401492L (en) 1984-03-16
YU40624B (en) 1986-02-28
GB1598628A (en) 1981-09-23
AR222797A1 (en) 1981-06-30
DE2824066A1 (en) 1978-12-14
ES478203A1 (en) 1979-06-01
SE8401491L (en) 1984-03-16
LU79725A1 (en) 1979-02-02
SE8401491D0 (en) 1984-03-16
NO152214B (en) 1985-05-13
JPS5639313B2 (en) 1981-09-11
IL54819A (en) 1983-03-31
HK38084A (en) 1984-05-11
YU129778A (en) 1983-02-28
FI69069B (en) 1985-08-30
MY8500453A (en) 1985-12-31

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