Patent GB-810304-A (GB)
Title: Improvements in or relating to amines
Inventor: ASHLEY JULIUS NICHOLSON
IPC: C07D213/64
Filed: 1955-09-01
Abstract: The invention comprises compounds of the general formula <FORM:0810304/IV (b)/1> wherein R1 and R2 are the same or different and are each a hydrogen atom or a lower alkyl, hydroxyalkyl (including polyhydroxyalkyl) or alkoxyalkyl group, R3 is hydrogen, methyl or a substituted or unsubstituted alkoxy group of not more than 4 carbon atoms, A1 is a saturated or ethylenically unsaturated hydrocarbon chain of 5-9 carbon atoms which is either unbranched or is substituted by one or more lower alkyl groups and R1 is a cyclic acylamido group of the formula <FORM:0810304/IV (b)/2> wherein X is the divalent radical necessary to complete a saturated or unsaturated heterocyclic ring which optionally contains further hetero atoms or substituents, including fused rings, but excluding a second carbonyl group adjacent to the nitrogen atom, and acid addition salts of these compounds and formaldehyde bisulphite derivatives of the compounds which are primarily amines.  The compounds are made by treating a compound of the formula <FORM:0810304/IV (b)/3> with a compound MR11, wherein Y is a tertiary amino group or a group convertible to a primary, secondary or tertiary amino group, A11 is the same as A1 or is a corresponding less-saturated hydrocarbon chain, Z is the residue of a reactive ester, such as a halogen atom, M is hydrogen or an alkali metal atom and R11 represents R1 or a group which can be converted thereto, and, if necessary treating the product to convert any of Y, A11 and R11 into R1R2N-, A1 or R1, respectively; alternatively a compound of the formula <FORM:0810304/IV (b)/4> is reacted with a compound of the formula Z-A11-R11 and the product is treated to convert Y, A11 and R11 into R1R2N-, A1 or R1, respectively. Suitably the group Y may be (a) an acylamido, carbonamido, nitro, nitroso, alkoxycarboxylamido, anil or arylazo group, convertible into a primary amino group; (b) an anil, alkoxycarbonylamido, acylamido or acylalkylamido group, convertible into a secondary amino group, or (c) a quaternary ammonium or acylalkylamido group, convertible into a tertiary amino group.  Also compounds of the general formula I containing a primary or secondary amino group are converted into products containing more highly substituted amino groups, for example by treatment with an alkylating agent or an alkylene oxide.  The compounds are used pharmaceutically in the treatment of bilharziasis.  In examples: (1) 5-p-nitrophenoxypentyl iodide (prepared by treating the bromide with sodium iodide) is reacted with the sodium salt of 2-pyridone, the resulting N-(5-p-nitrophenoxypentyl) pyrid-2-one is reduced with sodium sulphide to the p-amino derivative and subsequently with hydrogen in the presence of platinum to give N-(5-p-amino-phenoxypentyl)-piperid-2-one; (2) 1-p-amino-phenoxy-5-phthalimido-pentane is reduced with tin and hydrochloric acid to N-(5-p-amino-phenoxypentyl) phthalimidine, the o-methoxy derivative is similarly prepared, and (3) 1-p-acetamidophenoxy - 5 - bromopentane (prepared from p-acetamidophenol and 1:5-dibromopentane) is heated with the sodium salt of 3-oxo-2:3-dihydro-benzisothiazole and the resulting 1 - p - acetamidophenoxy - 5 - (3 - oxo-2:3 - dihydrobenzisothiazol - 2 - yl)-pentane is hydrolysed to 1-p-aminophenoxy-5-(3-oxo-2:3-dihydrobenzisothiazol-2-yl)-pentane which is purified via its methanesulphonate.  Specifications 808,952, and 809,023 are referred to.ALSO:Therapeutic compositions for the treatment of bilharziasis comprise compounds of the formula <FORM:0810304/VI/1> wherein R1 and R2 represent a hydrogen atom or a lower alkyl, hydroxyalkyl (including polyhydroxyalkyl) or alkoxyalkyl group, A1 represents a saturated or ethylenically unsaturated hydrogen chain of 5-9 carbon atoms optionally substituted by one or more lower alkyl groups, R1 represents a cyclic acylamido group of the formula <FORM:0810304/VI/2> wherein X is the divalent radical necessary to complete an N-heterocyclic oxo-substituted ring which may contain further hetero atoms or bear substitutents, including fused rings, but excluding a second carbonyl group adjacent to the nitrogen and R3 is hydrogen, methyl or a substituted or unsubstituted alkoxy group, and acid addition salts of these compounds and formaldehyde-bisulphite derivatives of those compounds which are primary amines, in association with a pharmaceutical carrier. Suitably the group R1 may be a 2-oxopiperidinophthalimido or 3 - oxo - 2 : 3 - dihydrobenzisothiazolyl-(2) group, specified compounds being N - (5 - p - aminophenoxypentyl) - piperid - 2 - one, N - (5 - p - aminophenoxypentyl) - phthalimidine and its o-methoxy derivative and 1-p-aminophenoxy - 5 - (3 - oxo - 2 : 3 - dihydrobenzisothiazol - 2 - yl) - pentane.  The active compounds may be admixed with liquid or solid diluents to provide elixirs, tablets, powders or capsules for oral administration or may be dissolved in a liquid diluent such as water for parenteral injection.  Specified solid diluents include starch, lactose, talc, stearic acid and magnesium stearate. Specifications 808,952 and 809,023 are referred to.