Patent GB-905186-A (GB)
Title: Pharmaceutical compositions for the treatment of malignant growths comprising amides
IPC: C07C233/34
Filed: 1960-12-30
Abstract: Amides of the general formula <FORM:0905186/IV (b)/1> (wherein R1 is CH2=CH - and R2 is CH2 = CR - in which R is a hydrogen atom or a C1-6 alkyl radical and n is a whole number from 1 to 8 and wherein when n is 1 R1 and R2 may both be allyl or 2-haloethyl radicals) may be prepared in the following ways: (1) When n is 1 and R1 and R2 are both vinyl radicals (R = hydrogen), by the interaction of 2 mols of acrylamide and 1 mol of formaldehyde to give N,N1-methylene-bis-acrylamide; (2) when n is 1 and R1 + R2 are different (R = C1-6 alkyl), by the interaction of 1 mol of acrylamide, 1 mol of a 2-alkyl-substituted acrylamide and 1 mol of formaldehyde in strong acid to give an N-(2-alkylpropeneamidomethyl) acrylamide; (3) by stepwise processes wherein (a) 1 mol of acrylamide is reacted with 1 mol of formaldehyde preferably in the presence of a base catalyst to give N-methylolacrylamide which is reacted with 1 mol of a 2-alkyl substituted acrylamide preferably in the presence of an acid catalyst, e.g. ZnCl2,Al2Cl6 or a mineral acid and, (b) 1 mol of a 2-alkyl-substituted acrylamide is reacted with 1 mol of formaldehyde preferably in the presence of a base catalyst to give an N-methylol-2-alkylpropeneamide which is reacted with 1 mol of acrylamide preferably in the presence of an acid catalyst, both of which are equivalent to and give the same products as process (2) above; (4) when n>1 and R is hydrogen, by the interaction of 2 mols of acrylolyl chloride with 2 mols of an a ,o -alkylene diamine in an inert solvent, and, when R is C1-6 alkyl, by the interaction of 1 mol of acryloyl chloride, 1 mol of a 2-alkyl-substituted acryloyl chloride and 1 mol of an a ,o -alkylene diamine in an inert solvent. These reactions may also be carried out stepwise (a) by reacting 1 mol of an a ,o -alkylene diamine or with 1 mol of acryloyl chloride in an inert solvent to give an N-acryloylalkylene diamine which is reacted with 1 mol of a 2-alkyl substituted acryloyl chloride in an inert solvent or (b) by reaction in an inert solvent of 1 mol of a 2-alkyl substituted acryloyl chloride with 1 mol of an a ,o -alkylene diamine to give an N-(2-alkylacryloyl) alkylene diamine which is reacted with 1 mol of acryloyl chloride in both series of reactions giving an N-acryloyl-N1-(2-alkylacryloyl) alkylene diamine; (5) when n is 1 and R1 and R2 are allyl or 2-haloethyl, by the interaction of 2 mols of 3-buteneamide or 2 mols of the appropriate 3-halopropionamide with 1 mol of formaldehyde in the presence of a strong acid.  Alternatively the appropriate nitrile may be used in place of the 3-butene- or 3-halopropion-amide when hydrolytic conditions are employed.  Where formaldehyde is used in the above reactions, it may be used in such forms as paraformaldehyde.ALSO:Pharmaceutical compositions for oral and parenteral administration and useful in the treatment of malignant growths in man and animals comprise a carrier and a compound of general formula <FORM:0905186/VI/1> wherein R1 is CH2=CH-and R2 is CH2=CR-wherein R is a hydrogen atom or C1-6 alkyl radical and n is a whole number from 1 to 8 and wherein when n is 1, R1 and R2 may both be allyl or 2-haloethyl radicals.  The compositions may be in conventional unit dosage form, e.g. a tablet, pill, capsule, powder, parenteral solution or suspension.