Patent GB-1025698-A (GB)
Title: Improvements in or relating to 5,6-dihydromorphanthridine derivatives
IPC: A61K31/55
Filed: 1963-09-12
Abstract: The invention comprises 5,6-dihydromorphanthridines of the formulae <FORM:1025698/C2/1> and <FORM:1025698/C2/2> wherein Y and Y1 are the same or different and each represents a hydrogen or halogen atom, or a C1- 6 alkoxy, C1- 6 alkyl, C1- 6 alkylthio or trifluoromethyl radical, R represents a hydrogen atom, or a C1- 6 alkyl, C2- 6 alkenyl, phenyl-C1- 6 alkyl, benzhydryl, trityl or phenyl-C2- 6 alkenyl radical, A represents an alkylene group and R1 and R2 are the same or different and each represents a hydrogen atom or a C1- 6 alkyl, C2- 6 alkenyl, phenyl, phenyl-C1- 6 alkyl, benzhydryl, trityl, cycloalkyl having 5-7 ring carbon atoms, cycloalkyl-C1- 6 alkyl in which the cycloalkyl has 5 to 7 ring carbon atoms, carbethoxy or s-methylthio-carbonyl radical, or <FORM:1025698/C2/3> represents a morpholino, pyrrolidino, piperidino, N - C1- 6 alkyl - piperazino, N - (phenyl - C1- 6 alkyl)-piperazino or N-(hydroxy-C1- 6 alkyl)-piperazino group, and B represents a single bond or a C1- 6 alkylene radical and Am represents a pyridyl, pyrrolidyl, piperidyl, N-C1- 6 alkyl-piperidyl, N - (phenyl-C1- 6 alkyl) - piperidyl, N - C1- 6 alkyl - pyrrolidyl or N - (phenyl - C1- 6 alkyl) - pyrrolidyl group, B being an alkylene group when Am is bonded to the 2-position of the ring, and pharmaceutically acceptable non-toxic acid addition salts thereof.  Compounds of the Formula I wherein R, R1 and R2 are all other than hydrogen are prepared by reacting a compound of the formula <FORM:1025698/C2/4> with a compound of the formula <FORM:1025698/C2/5> wherein M is an alkali metal, X is a reactive halogen atom or a p-toluene sulphonyloxy group and Y, Y1, A, R, R1 and R2 are as defined above except that R, R1 and R2 are not hydrogen. Compounds of the Formula I where R is other than hydrogen are prepared by reacting a compound of the formula <FORM:1025698/C2/6> with a compound of the formula <FORM:1025698/C2/7> wherein X, Y, Y1, R, R1 and R2 are as defined above except that R is not hydrogen.  Compounds of the Formula I in which at least one of R, R1 and R2 is trityl can be treated with a weak acidic solution to split off the trityl group and produce compounds in which R, R1 and/or R2 is hydrogen.  Compounds of the Formula I in which R1 or R2 is a benzyl group can be converted to the corresponding compounds by debenzylation using a chloroformic acid ester or chlorothioformic ester to form a carbamate and then hydrolysing to cleave the acyloxy or acylthiol group.  Compounds of the Formula II, where R is other than hydrogen are prepared by reacting a compound of the Formula III above with a compound of the formula X-B-Am wherein X, M, Y, Y1, B, R and Am are as defined above except that R is not hydrogen.  Compounds of the Formula III are prepared by reacting an appropriately 5-substituted-5,6-dihydromorphanthridine with an alkali metal alkyl or aryl compound.  Compounds of the Formula IV are prepared by reacting a compound of Formula III with a compound of the formula <FORM:1025698/C2/8> or X-A-O-CH2#f to produce an ether of the formula <FORM:1025698/C2/9> or <FORM:1025698/C2/10> cleaving the tetrahydropyranyl residue or benzyloxy group therefrom to produce an alcohol of the formula <FORM:1025698/C2/11> and thereafter reacting the alcohol with phosphorus pentachloride, thionyl chloride or p-toluene-sulphonyl chloride.  Pharmaceutical compositions having anticholinergic, analgetic, antispasmodic, antidepressant and tranquilizing activity comprise a compound of the invention together with a pharmaceutical carrier.  The compositions may be in the form of solutions, powders or tablets.