GB1094985A - Amidine derivatives, processes for their preparation, and compositions incorporating them - Google Patents

Amidine derivatives, processes for their preparation, and compositions incorporating them

Info

Publication number
GB1094985A
GB1094985A GB27989/64A GB2798964A GB1094985A GB 1094985 A GB1094985 A GB 1094985A GB 27989/64 A GB27989/64 A GB 27989/64A GB 2798964 A GB2798964 A GB 2798964A GB 1094985 A GB1094985 A GB 1094985A
Authority
GB
United Kingdom
Prior art keywords
acid
treating
compound
methylphenoxy
chloro
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
Application number
GB27989/64A
Inventor
Harold Francis Hodson
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.)
Wellcome Foundation Ltd
Original Assignee
Wellcome Foundation Ltd
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
Application filed by Wellcome Foundation Ltd filed Critical Wellcome Foundation Ltd
Priority to GB27989/64A priority Critical patent/GB1094985A/en
Priority to IL23830A priority patent/IL23830A/en
Priority to LU48971A priority patent/LU48971A1/xx
Priority to DE19651518227 priority patent/DE1518227C3/en
Priority to BE666420D priority patent/BE666420A/xx
Priority to DK342865AA priority patent/DK125704B/en
Priority to AT614165A priority patent/AT287674B/en
Priority to ES0315014A priority patent/ES315014A1/en
Priority to FI1595/65A priority patent/FI42714B/fi
Priority to NL656508754A priority patent/NL142592B/en
Priority to FR23801A priority patent/FR5397M/fr
Priority to CH956365A priority patent/CH535207A/en
Priority to SE08956/65A priority patent/SE333728B/xx
Priority to FR23800A priority patent/FR1455203A/en
Priority to BR171014/65A priority patent/BR6571014D0/en
Priority to GB54489/65A priority patent/GB1145278A/en
Priority to FR88378A priority patent/FR93255E/en
Priority to DE1593728A priority patent/DE1593728C3/en
Priority to BE691597D priority patent/BE691597A/xx
Priority to CH1845466A priority patent/CH556829A/en
Priority to NL666618082A priority patent/NL151068B/en
Priority to LU52665D priority patent/LU52665A1/xx
Publication of GB1094985A publication Critical patent/GB1094985A/en
Priority to US05/437,738 priority patent/US3987158A/en
Expired legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C257/00—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines
    • C07C257/10—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines
    • C07C257/14—Compounds containing carboxyl groups, the doubly-bound oxygen atom of a carboxyl group being replaced by a doubly-bound nitrogen atom, this nitrogen atom not being further bound to an oxygen atom, e.g. imino-ethers, amidines with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. amidines having carbon atoms of amidino groups bound to acyclic carbon atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention comprises compounds of the formula <FORM:1094985/C2/1> wherein R1 and R2 are the same or different and each is phenyl or thien-2-yl which may be substituted with halogen C1-C4 alkyl, C1-C4 alkoxy, hydroxy, C1-C4 alkylthio, C1-C4 alkylsulphonyl or C1-C4 alkylsulphinyl, A1 is a divalent straight or branched chain C2-C6 alkylene group containing one or two O or S atoms, provided that there are at least 2 carbon atoms between the divalent atom or atoms and the-NH-group; and A2 is a divalent straight or branched C1-C4 alkylene group and acid addition salts thereof. They may be prepared by reacting NH3 with a compound of the formula <FORM:1094985/C2/2> wherein Y1 is halogen or SH, alkylthio or alkoxy group; or by reacting a primary amine R1.A1.NH2 with an imidocarbonyl compound of the formula <FORM:1094985/C2/3> wherein Y2 is a hydrogen and Y3 is NH2, SH alkylthio or alkoxy; or Y2 and Y3 form a bond; or by reacting an imidocarbonyl compound of the formulae, the two forms being tautomeric: R2.A2.C(:NOH).NH.A1.R1 R2.A2.C(NH.OH): N.A1.R1 with a reducing agent. Examples are given for the production of amidines of Formula I. 2 - (4 - Chloro - 3 - methylphenoxy) - ethylamine is obtained by treating 4-chloro-3-methylphenol with 1,2-dibromoethane in the presence of NaOH giving 1-bromo-(41-chloro-31-methylphenoxy) ethane, treating this compound with potassium phthalimide, and then treating the phthalimide derivative with hydrazine hydrate in the presence of ethanol and isolating the above amine. The following amines may be obtained in a similar manner: 2-31-methoxy-, -methyl-, or -chloro-phenoxyethylamine, 3-31-methoxyphenoxypropyl and 4-31-methoxyphenoxybutylamine. 2-Phenoxypropylamine is obtained by treating 2-chloropropionitrile with phenol in the presence of K2CO3, KI and methylethyl ketone giving 2-phenoxypropionitrile, and reducing the nitrile with LiAlH4. 2-(Substituted-phenoxy) propylamines are obtained in a similar manner. 1 - (3 - Methylphenoxy) prop - 2 - ylamine is obtained by reacting chloroacetone with 3-methylphenol in the presence of K2CO3, KI and ethyl methyl ketone giving 1-(3-methyl-phenoxy)-propan-2-one, converting this ketone to its oxime and reducing with LiAlH4. 1(21 or 31 - methoxyphenoxy) prop - 2 - ylamines 2-phenoxybut - 3 - ylamine and 2 - 31 - methylphenoxy-but-3-ylamine are obtained in a similar manner. 2-Benzyloxypropylamine is obtained by treating sodium 2-aminopropoxide in toluene with benzyl chloride. 2-31-Methylbenzyloxypropylamine and 2-21-thenyloxypropylamine are obtained in a similar manner. 4 - Fluorophenyl - acetamidine p - toluenesulphonate is obtained by treating 4-fluorophenylacetonitrile with hydrogen chloride followed by ethanolic ammonia. Phenylacetamidine p-toluenesulphonate and 2- or 4-methyl-, or 3,4-dimethyl-phenyl-acetamidine are obtained similarly. 3 - Methoxy - phenylacetamidine hydrochloride and other substituted phenylacetamidine hydrochlorides are obtained by treating the appropriate phenylacetonitrile in ethanol with hydrogen chloride followed by ethanolic ammonia. Pharmaceutical compositions comprise the compounds of the invention and the acid addition salts thereof in admixture with an acceptable carrier therefore. Acids used to form the acid addition products may be hydrochloric acid, hydriodic acid, sulphuric acid, lactic acid, citric acids, tartaric acids, succinic acid, oxalic acid, p-toluene-sulphonic acid, p-chlorobenzene-sulphonic acid and maleic acid. The compositions may be administered orally as a draft in water or in a syrup; in capsules or cachets in the dry state, or in tablet form; parenterally in unit dose or multi-dose containers in aqueous or non-aqueous injection solutions which may contain anti-oxidants, buffers, bacteriostats and solutes which render the compound or salt isotonic with the blood. Extemporaneous injection solutions may be made from sterile powders, granules or tablets. The compound or salt may be presented suppositories or pessaries by incorporation in a suppository base.
GB27989/64A 1964-07-07 1964-07-07 Amidine derivatives, processes for their preparation, and compositions incorporating them Expired GB1094985A (en)

Priority Applications (23)

Application Number Priority Date Filing Date Title
GB27989/64A GB1094985A (en) 1964-07-07 1964-07-07 Amidine derivatives, processes for their preparation, and compositions incorporating them
IL23830A IL23830A (en) 1964-07-07 1965-06-29 N-substituted phenylalkyl and thienyl-alkyl amidines,their preparation,and compositions containing them
LU48971A LU48971A1 (en) 1964-07-07 1965-07-02
DE19651518227 DE1518227C3 (en) 1964-07-07 1965-07-05 Substituted amidines and processes for their preparation
BE666420D BE666420A (en) 1964-07-07 1965-07-05
DK342865AA DK125704B (en) 1964-07-07 1965-07-06 Analogous process for the preparation of an amidine or an acid addition salt thereof.
AT614165A AT287674B (en) 1964-07-07 1965-07-06 Process for the preparation of new amidines and their acid addition salts
ES0315014A ES315014A1 (en) 1964-07-07 1965-07-06 Procedures for the preparation of an amidine or a corresponding acid addition salt. (Machine-translation by Google Translate, not legally binding)
FI1595/65A FI42714B (en) 1964-07-07 1965-07-06
CH956365A CH535207A (en) 1964-07-07 1965-07-07 5-Hydroxytryptamine diarylamidines antagonists
FR23801A FR5397M (en) 1964-07-07 1965-07-07
NL656508754A NL142592B (en) 1964-07-07 1965-07-07 PROCESS FOR THE PREPARATION OF AMIDINS OR ACID-ADDITIONAL SALTS DERIVED THEREOF, ACTING AS ANTAGONISTS OF 5-HYDROXYTRYPTAMINE, AND OF PHARMACEUTICAL PREPARATIONS CONTAINING AT LEAST ONE OF THESE COMPOUNDS.
SE08956/65A SE333728B (en) 1964-07-07 1965-07-07
FR23800A FR1455203A (en) 1964-07-07 1965-07-07 Process for the preparation of certain substituted amidines
BR171014/65A BR6571014D0 (en) 1964-07-07 1965-07-26 PROCESS TO PREPARE AN AMIDINE
GB54489/65A GB1145278A (en) 1964-07-07 1965-12-23 Amidine derivatives, processes for their preparation, and compositions incorporating them
FR88378A FR93255E (en) 1964-07-07 1966-12-21 Process for the preparation of certain substituted amidines.
DE1593728A DE1593728C3 (en) 1964-07-07 1966-12-21 Substituted amidines and process for their preparation
BE691597D BE691597A (en) 1964-07-07 1966-12-22
CH1845466A CH556829A (en) 1964-07-07 1966-12-23 METHOD OF PRODUCING AN AMIDINE.
NL666618082A NL151068B (en) 1964-07-07 1966-12-23 METHOD OF PREPARING A MEDICINAL PRODUCT WITH A 5-HYDROXYTRYPTAMINE ANTAGONATING ACTION AND THE OBTAINED PREPARED MEDICINAL PRODUCT, AND A PROCESS FOR PREPARING A MEDICINAL PRODUCT FOR RECORDING IN SUCH A MEDICINAL MEDICINAL PRODUCT.
LU52665D LU52665A1 (en) 1964-07-07 1967-05-12
US05/437,738 US3987158A (en) 1964-07-07 1974-01-29 Serotonin antagonists

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB27989/64A GB1094985A (en) 1964-07-07 1964-07-07 Amidine derivatives, processes for their preparation, and compositions incorporating them
GB4417164 1964-10-29

Publications (1)

Publication Number Publication Date
GB1094985A true GB1094985A (en) 1967-12-13

Family

ID=26259114

Family Applications (1)

Application Number Title Priority Date Filing Date
GB27989/64A Expired GB1094985A (en) 1964-07-07 1964-07-07 Amidine derivatives, processes for their preparation, and compositions incorporating them

Country Status (13)

Country Link
AT (1) AT287674B (en)
BE (1) BE666420A (en)
BR (1) BR6571014D0 (en)
CH (1) CH535207A (en)
DK (1) DK125704B (en)
ES (1) ES315014A1 (en)
FI (1) FI42714B (en)
FR (2) FR1455203A (en)
GB (1) GB1094985A (en)
IL (1) IL23830A (en)
LU (1) LU48971A1 (en)
NL (1) NL142592B (en)
SE (1) SE333728B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006021564A1 (en) * 2004-08-26 2006-03-02 Neurosearch A/S Novel substituted aryloxy alkylamines and their use as monoamine neurotransmitter re-uptake inhibitors

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1307978A (en) * 1969-02-28 1973-02-21 Wellcome Found Amidines processes for their preparation and pharmaceutical compo sitions incorporating the same
EP0947494A1 (en) * 1998-03-30 1999-10-06 F. Hoffmann-La Roche Ag Derivatives of phenoxy acetic acid and phenoxymethyltetrazole having antitumor activity

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006021564A1 (en) * 2004-08-26 2006-03-02 Neurosearch A/S Novel substituted aryloxy alkylamines and their use as monoamine neurotransmitter re-uptake inhibitors
US7973082B2 (en) 2004-08-26 2011-07-05 Neurosearch A/S Substituted aryloxy alkylamines and their use as monoamine neurotransmitter re-uptake inhibitors

Also Published As

Publication number Publication date
FR1455203A (en) 1966-04-01
IL23830A (en) 1969-09-25
CH535207A (en) 1973-03-31
SE333728B (en) 1971-03-29
BR6571014D0 (en) 1973-08-02
FI42714B (en) 1970-06-30
AT287674B (en) 1971-02-10
ES315014A1 (en) 1966-02-01
LU48971A1 (en) 1965-09-02
FR5397M (en) 1967-09-25
DK125704B (en) 1973-03-26
DE1518227B2 (en) 1975-09-25
DE1518227A1 (en) 1969-04-10
BE666420A (en) 1966-01-05
NL142592B (en) 1974-07-15
NL6508754A (en) 1966-01-10

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