Patent GB-1045180-A (GB)
Title: Quinazoline derivatives
Inventor: DAVOLL JOHN
IPC: C07D239/95
Filed: 1963-09-20
Abstract: Novel 2,4-diaminoquinazolines of the formula <FORM:1045180/C2/1> and acid addition salts thereof, where A represents -NH2, -N = CHR or - NHCH2R, the term R signifying a phenyl group; a mono-, dior tri-(lower alkyl)phenyl, mono-, or di(halo)-phenyl, hydroxyphenyl, mono-, di- or tri-(lower alkoxy)phenyl, carboxyphenyl, carb(lower alkoxy) phenyl, nitrophenyl, aminophenyl, mono-or di-(lower alkyl) aminophenyl, or acetaminophenyl group; a naphthyl group; a halonaph-thyl, hydroxynaphthyl, nitronaphthyl, aminonapththy or lower alkoxynaphthyl group; or a furyl or pyridyl group, and in particular 2,4,6-triaminoquinazoline, and the monohydrochloride, 2,4 - diamino - 6 - (o - chlorobenzylideneamino) - quinazoline, 2,4 - diamino - 6 - benzylideneaminoquinazoline, 2,4 - diamino - 6 -(2 - naphthylmethyleneamino) -quinazoline, 2,4 - diamino - 6 - (o - methylbenzylideneamino)-quinazoline, 2,4 - diamino - 6 - (p - dimethylaminobenzylideneamino)quinozoline, 2,4 - diamino - 6 - benzylaminoquinazoline, and the monohydrochloride, 2,4 - diamino - 6 - (2 - naphthylmethylamino) - quinazoline, 2,4 - diamino - 6 - (2,4,6 - trimethylbenzylamino) - quinazoline, 2,4 - diamino - 6 - (p - ethoxybenzylamino) - quinazoline, 2,4 - diamino - 6 - (p - chlorobenzylamino) - quinazoline, 2,4 - diamino-6 - (o - methylbenzylamino) - quinazoline, 2,4 - diamino - 6 - (p - methylbenzylamino) - quinazoline, 2,4 - diamino - 6 - (3,4 - dichlorobenzylamino) - quinazoline, may be made from 2,4,6-triaminoquinazoline which itself may be obtained by using 2,4-diamino-6-nitroquinazoline for example with a hydrogen gas and a metal hydrogenation catalyst or using a stannous salt in mineral or organic acid; the Schiff base intermediate compounds may be obtained by reacting an aldehyde with an equimolar quantity of 2,4,6-triaminoquinazoline and the Schiff base may be further reduced to obtain the corresponding methyl amino compound.  The products themselves or the acid addition salts thereof, particularly the pharmaceutically acceptable acid salts thereof together with a pharmaceutical diluent or excipient made up especially into dosage units for oral or parenteral administration are stated to possess antiviral, diuretic, anti-bacterial, anti-parasitic, anthelmintic, anti-malarial, anti-trypanosomatic, activities.  Specified dosage units include tablets, pills, sachets, encapsulated powder, sterile injectable solutions and suspensions. Salts specified include the hydrochloride, hydrobromide or hydriadide, sulphate, phosphate, carbonate, succinate, benzoate, acetate, citrate, malate, maleate p-toluene sulphonate, gluconate, ascorbate, benzene sulphonate, and sulphonate, as well as fluorescein, and methy-lene-bis-hydroxy naphthoic acid; specified intermediates described include 2,4-diamino-6-nitroquinazoline, obtained by the nitration of 2,4-diaminoquinazoline, the Schiff's base products from p-tolualdehyde, o-tolualdehyde, 2-naphthaldehyde, furfuraldehyde, 2-pyridinecarboxaldehyde, 4-pyridone carboxaldehyde, salicaldehyde, or m- or p-hydroxy-benzaldehyde p-fluorobenzaldehyde, o-chlorobenzaldehyde, m-chlorobenzaldehyde, 2,4-dichlorobenzaldehyde, 3,4-dichlorobenzaldehyde, anisaldehyde. The description also includes details of the preparation of 3,11-dihydroxy-4,41-methylenedi-2-naphthoic acid, 3,61-dihydroxy-4,51-methylenedi-2-naphthoic acid, 4,41-ethylenebis-7-bromo-3-hydroxy-2-naphthoic acid.