GB1598629A - N-cyano-n'-alkynyl-s-substituted isothioureas - Google Patents
N-cyano-n'-alkynyl-s-substituted isothioureas Download PDFInfo
- Publication number
- GB1598629A GB1598629A GB27637/79A GB2763779A GB1598629A GB 1598629 A GB1598629 A GB 1598629A GB 27637/79 A GB27637/79 A GB 27637/79A GB 2763779 A GB2763779 A GB 2763779A GB 1598629 A GB1598629 A GB 1598629A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- methyl
- butyn
- cyano
- hydrogen
- Prior art date
- 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
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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
Description
PATENT SPECIFICATION () 1 598 629
( 21) Application No 27637/79 ( 22) Filed 26 May 1978 ( 62) Divided out of No1598628 ( 1 ( 31) Convention Application No 803009 ( 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 CL 3 C 07 C 157/14 ( 52) Index at acceptance C 2 C 202 20 Y 30 Y 320 326 373 37 Y 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 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-cyanoN'-{ 2 l( 4 methyl 5 imidazolyl)methylthiol ethyl}-N"-alkynylguanidines which are H 2 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 R 2 S-CNH-R 1 III wherein R' is a straight or branched chain alkynyl group containing from 3 to 9 carbon atoms and R 2 is C,_ 9 alkyl, aryl, substituted aryl, aralkyl, -CH 2 CN, 15 -CHCOOH or -CH 2 COOR' wherein R' is C,_ 9 lower alkyl.
In a preferred embodiment, RI of the compound of formula III is -CHC=CR 4 CH 3 in which R 4 is hydrogen or methyl; in another preferred embodiment RI is (CH 2)n C=-CR 4 20 in which N is an integer of from I to 6 and R 4 is hydrogen or methyl; in another preferred embodiment R' is CH 3 I -C-C=_CR 4 CH 3 in which R 4 is hydrogen or methyl.
In a more preferred embodiment, RI is a propargyl, 2-butyn-1-yl, 3-butynl-yl, 25 2-methyl-3-butyn-2-yl, or 4-pentyn-l-yl group.
The compounds of the present invention are intermediates in the preparation of compounds of the formula CHN C N CH 2 SCH 2 CH 2 NHCNH-R H wherein R' is a straight or branched chain alkynyl group containing from 3 to 9 carbon atoms, or non-toxic pharmaceutically acceptable acid addition salts 5 thereof.
The compounds of formula I are described and claimed in our copending patent application No 23611/78 Serial No 1,598,628.
The compounds of formula I and salts thereof may be prepared by reacting a compound of the formula 10 CH 3 CH 2 SCH 2 CH 2 NH 2 II H or an acid addition salt thereof, with a compound of the formula NCN R 2 S-CNH-R' III wherein R' and R 2 are as above defined, and, if desired, converting the resulting compound of formula I in basic form or an acid addition salt thereof to the 15 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 3 N < NCN -N 7 \H 2 SCH 2 CH 2 NH 2 + RS-CNHCH 2 C-CH H / j CH 35 HC HN CH 2 SCH 2 CH 2 NHCNHCH 2 C-CH H wherein R 2 is as above defined 20 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:1,598,629 NCN II (R 2 S)2 C=NCN+ H 2 NR'-R 2 S-CNHR 1 +R 25 H The present invention will be further described with reference to the following Examples.
EXAMPLE I
N-Cyano-N'-propargyl-S-methylisothiourea 5 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 10 A solution of dimethyl cyanodithioiminocarbonate ( 10 00 g, 0 684 mole) and 2butyn-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.
N 1,1 Diehlrp EXAMPLE 3 15 N-( 1,1 -Dimethylpropargyl)-N'-cyano-S-methylisothiourea The general procedure of Example 2 is repeated except that the 2-butyn-1ylamine utilized therein is replaced by an equimolar amount of 1,1 dimethylpropargylamine, and the title product is thereby produced.
EXAMPLE 4 20
N-( l -Methylpropargyl)-N'-cyano-S-methylisothiourea The general procedure of Example 2 is repeated except that the 2-butyn-lylamine utilized therein is replaced by an equimolar amount of 1methylpropargylamine, and the title product is thereby produced.
EXAMPLE 5 25
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 30 EXAMPLE 6
N-Cyano-N'-( 2-butyn 1 -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 35 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 3butyn-l 40 yl-amine, and the title compound is thereby produced.
EXAMPLE 8
N-Cyano-N'-( 4-pentyn l-yl)-S-methylisothiourea The general procedure of Example 5 is repeated, except that the propargylamine utilzed therein is replaced by an equimolar amount of 4pentyn 1 45 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 50 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 by an equimolar amount of lmethylpropargylamine, and the title compound is thereby produced 5
Claims (1)
- WHAT WE CLAIM IS:-1 A compound of the formula NCN 11 R 2 S-CNH-R 1 wherein RI is a straight or branched chain alkynyl group containing from 3 to 9 carbon atoms, inclusive, and R 2 is C 1 _ 9 alkyl, aryl, substituted aryl, aralkyl, 10 -CH 2 CN, -CN 2 COOH or -CH 2 COOR' where R' is C 1 _qalkyl.2 A compound as claimed in claim I in which R' is (CH 2)n-=CR 4 wherein N is an integer of from 1 to 6, inclusive, and R 4 is hydrogen or methyl 15 3 A compound as claimed in claim 1 in which R 1 is 15 -CHC=CR 4 CH 3 wherein R 4 is hydrogen or methyl.4 A compound as claimed in claim I in which R' is CH 3 C_-CR 4 CH 3 wherein R 4 is hydrogen or methyl 20 A compound as claimed in claim 1 wherein RI is a propargyl, 2-butyn-l-yl, 3-butyn-1-yl, 2-methyl-3-butyn-2-yl, or 4-pentyn-l-yl 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.7 A compound as claimed in claim 1 whenever prepared by a process as 25 claimed in claim 6.BOULT, WADE & TENNANT, 27 Furnival Street, London EC 4 A IPQ.Printed for Her Majesty's Stationery Office, by the Courier Press, Leamington Spa, 1981 Published by The Patent Office, 25 Southampton Buildings, London, WC 2 A l AY, from which copies may be obtained.1,598629
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 |
|---|---|
| GB1598629A true GB1598629A (en) | 1981-09-23 |
Family
ID=27419995
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB27637/79A Expired GB1598629A (en) | 1977-06-03 | 1978-05-26 | N-cyano-n'-alkynyl-s-substituted isothioureas |
| GB23611/78A Expired GB1598628A (en) | 1977-06-03 | 1978-05-26 | Guanidine derivatives |
| GB18923/80A Expired GB1598630A (en) | 1977-06-03 | 1978-05-26 | N-cyano-n'-alkynyl-n''-(2-mercaptoethyl)-guanidines |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB23611/78A Expired GB1598628A (en) | 1977-06-03 | 1978-05-26 | Guanidine derivatives |
| GB18923/80A Expired GB1598630A (en) | 1977-06-03 | 1978-05-26 | N-cyano-n'-alkynyl-n''-(2-mercaptoethyl)-guanidines |
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) | GB1598629A (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 (7)
| 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 |
| JPS57134318A (en) * | 1981-02-12 | 1982-08-19 | Nissan Motor Co Ltd | Air mixing construction of air conditioner |
| JPS5848516U (en) * | 1981-09-30 | 1983-04-01 | 日産車体株式会社 | Vehicle air conditioner |
| 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)
| 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 |
| GB1533380A (en) * | 1974-09-02 | 1978-11-22 | Smith Kline French Lab | Process for the preparation of heterocyclic substituted thioureas and h-cyanoguanidines |
| GB1531231A (en) * | 1974-09-02 | 1978-11-08 | Smith Kline French Lab | Process for the production of cyanoguanidine derivatives |
| GB1531221A (en) * | 1974-09-02 | 1978-11-08 | Smith Kline French Lab | Process for preparing guanidine derivatives |
-
1978
- 1978-05-25 CA CA304,045A patent/CA1110251A/en not_active Expired
- 1978-05-25 NZ NZ187376A patent/NZ187376A/en unknown
- 1978-05-26 GB GB27637/79A patent/GB1598629A/en not_active Expired
- 1978-05-26 CY CY1230A patent/CY1230A/en unknown
- 1978-05-26 GB GB23611/78A patent/GB1598628A/en not_active Expired
- 1978-05-26 CY CY1231A patent/CY1231A/en unknown
- 1978-05-26 CY CY1229A patent/CY1229A/en unknown
- 1978-05-26 GB GB18923/80A patent/GB1598630A/en not_active Expired
- 1978-05-29 GR GR56374A patent/GR73860B/el unknown
- 1978-05-29 LU LU79725A patent/LU79725A1/en unknown
- 1978-05-31 FI FI781737A patent/FI69069C/en not_active IP Right Cessation
- 1978-05-31 DK DK243178A patent/DK243178A/en not_active Application Discontinuation
- 1978-05-31 AR AR272401A patent/AR222797A1/en active
- 1978-05-31 YU YU01297/78A patent/YU129778A/en unknown
- 1978-05-31 IL IL54819A patent/IL54819A/en unknown
- 1978-05-31 NL NL7805935A patent/NL7805935A/en not_active Application Discontinuation
- 1978-06-01 DE DE19782824066 patent/DE2824066A1/en not_active Withdrawn
- 1978-06-02 ES ES470474A patent/ES470474A1/en not_active Expired
- 1978-06-02 NO NO781928A patent/NO152214C/en unknown
- 1978-06-02 CH CH609278A patent/CH641167A5/en not_active IP Right Cessation
- 1978-06-02 IE IE1112/78A patent/IE47543B1/en unknown
- 1978-06-02 JP JP6590078A patent/JPS543067A/en active Granted
- 1978-06-02 HU HU811135A patent/HU186766B/en unknown
- 1978-06-02 FR FR7816601A patent/FR2401143A1/en active Granted
- 1978-06-02 SE SE7806525A patent/SE443784B/en unknown
- 1978-06-05 DD DD78205794A patent/DD140038A5/en unknown
-
1979
- 1979-03-01 ES ES478202A patent/ES478202A1/en not_active Expired
- 1979-03-01 ES ES478203A patent/ES478203A1/en not_active Expired
- 1979-03-05 YU YU530/79A patent/YU41620B/en unknown
- 1979-05-16 NO NO791637A patent/NO791637L/en unknown
- 1979-10-26 AR AR278645A patent/AR222503A1/en active
- 1979-11-23 FR FR7928943A patent/FR2436138A1/en active Granted
-
1982
- 1982-09-27 YU YU2155/82A patent/YU40625B/en unknown
- 1982-09-27 YU YU2154/82A patent/YU40624B/en unknown
-
1983
- 1983-09-12 NO NO833255A patent/NO151824C/en unknown
- 1983-10-07 CH CH549283A patent/CH644591A5/en not_active IP Right Cessation
-
1984
- 1984-01-30 SG SG85/84A patent/SG8584G/en unknown
- 1984-02-10 KE KE3373A patent/KE3373A/en unknown
- 1984-03-16 SE SE8401491A patent/SE8401491D0/en not_active Application Discontinuation
- 1984-03-16 SE SE8401492A patent/SE8401492L/en not_active Application Discontinuation
- 1984-05-03 HK HK380/84A patent/HK38084A/en unknown
- 1984-05-03 HK HK381/84A patent/HK38184A/en unknown
- 1984-05-03 HK HK382/84A patent/HK38284A/en unknown
-
1985
- 1985-12-30 MY MY453/85A patent/MY8500453A/en unknown
- 1985-12-30 MY MY451/85A patent/MY8500451A/en unknown
- 1985-12-30 MY MY452/85A patent/MY8500452A/en unknown
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |