Patent ES-301103-A1 (ES)
Title: New dihydrothieno[3,2-d]pyrimidines
IPC: C07D495/04
Filed: 1964-06-16
Abstract: The invention comprises compounds of the Formula I wherein R represents a halogen atom or an aryl a free hydroxy or a C1- 5 alkylmercapto group or a group of the formula -NR3R4 (in which R3 represents a C1- 6 alkyl or an aralkyl group and R4 represents a hydrogen atom or a C1- 6 alkyl group or R3 and R4, together with the adjacent nitrogen atom, represent a heterocyclic ring which may contain a further hetero-atom and which may be substituted with a C1- 3 alkyl group or an aryl group) R1 represents a hydrogen or halogen atom, or a mercapto group, a hydroxy group (which may be free or substituted by a C1- 6 alkyl, C2- 6 alkenyl or (C1- 6 alkoxy)-C1- 6 alkyl group) or a group of the formula -NR5R6 (in which R5 represents a hydrogen atom or an amine, C1- 6 alkyl, C2- 6 alkenyl, C1- 6 hydroxyalkyl, (C1- 6 alkoxy) C1- 6 alkyl, [di-(C1- 6 alkyl) amino] C1- 6 alkyl, aryl, aralkyl or cycloalkyl group and R6 represents a hydrogen atom or a C1- 6 alkyl, C2- 6 alkenyl or C1- 6 hydroxyalkyl group or R5 and R6, together with the adjacent nitrogen atom, represent a heterocyclic ring which may contain a further hetero-atom and which may be substituted by a C1- 3 alkyl group) R2 represents (where present) a C1- 10 alkyl or phenyl group and n represents 0 or 1, and (where at least one of R, R1 and R2 represents a basic group) non-toxic acid addition salts thereof, and (where R and/or R1 represents a free hydroxy group or R1 represents a free mercapto group) non-toxic salts with bases a process for the preparation of compounds of the Formula I (in which R1 represents a free hydroxy group) where a compound of the Formula II (in which X represents a carboxylic ester group and Y represents an oxo group) is reacted with a compound of the formula R-C(NH2)=Z or a tautomer thereof of the formula R-C(=NH)-ZH (in which Z represents an imino group) a process for the preparation of compounds of the Formula I wherein a compound of the Formula V (in which at least one of A and A1 represents a halogen atom or a free or C1- 5 alkyl substituted mercapto group and the other, if not representing a halogen atom or a free or C1- 5 alkyl substituted mercapto group, represents any of the other groups which may be represented by R and R1) is reacted with a compound of the formula R7H, whereby A1 is replaced by R7, and A either remains unreplaced or is replaced by R7 in the same reaction stage or a further reagent R8H is added to replace A by a group R8 (where R7 and R8, the same or different), represent any of the atoms or groups which may be represented by R and R1 other than a hydrogen or halogen atom or an alkyl, aryl or aralkyl group the process for preparing compounds of the Formula I (in which R is as defined above, with the exception of a hydroxy group, and R1 represents a hydroxy group substituted by a C1- 6 alkyl, C2- 6 alkenyl or (C1- 6 alkoxy)-C1- 6 alkyl group) in which a compound of the Formula I in which R and/or R1 represents a free hydroxy group is reacted with an appropriate alkylating, alkenylating or aralkylating agent the process for the preparation of compounds of the Formula I (in which R1 represents an amino group of the formula -NR3R4, wherein R3 and R4 are as defined above except that R3 does not represent an aryl or pyridyl group and R3 and R4 do not together represent a heterocylic group) in which the corresponding compound of the Formula I, in which R1 represents a free amino group, is reacted with an appropriate alkylating, alkenylating or aralkylating agent and the process for the preparation of compounds of the Formula I (in which R and/or R1 represents a hydrogen atom) in which a corresponding compound of the Formula I, in which R and/or R1 represent a mercapto group, is reduced. <FORM:1072413/C2/1> Dihydrothieno[3,2-d]pyrimidines of the Formula V may be prepared by the method described above, in which a compound of the Formula II is reacted with a compound of the formula R-C(NH2)=Z or its tautomer of the formula R-C(:NH)-ZH, or, where A and/or A1 represent free or C1- 5 alkyl substituted mercapto groups, by cyclization, e.g. by reaction of a 3 - imino - tetrahydrothiophene - 2 - carboxylic acid thioamide with a thiourea, by reacting the dihydroxy compound with P2S5, followed if desired by alkylation or from the corresponding halogen compound by reaction with thiourea, an alkali metal hydrosulphide or an alkali metal mercaptide, or, where A and/or A1 represent halogen atoms, cyclizing a compound of the Formula II (in which X represents a carbalkoxy group) with urea and converting the resulting 2,4-dihydroxy-dihydrothieno[3,2-d]pyrimidine into the dihalo compound by known methods. Therapeutic compositions, with cardiovascular, sedative, analgesic diuretic, cytostatic, bacteriostatic, antiphlogistic and/or antipyretic activity, which may take the forms of capsules, dragees, powders, drop solutions, suspensions, solutions, ampoules or suppositories, for oral, parenteral or rectal administration, comprise compounds of the Formula I or (where at least one of R, R1 and R2 represents a basic group) non-toxic acid addition salts thereof or (where R and/or R1 represents a free hydroxy group or R1 represents a free mercapto group) non-toxic salts thereof with bases, together with a pharmaceutical carrier.