Abstract: This invention relates to novel purine nucleoside phosphorylase inhibitors, to the methods and intermediates for their preparation and to their use as immuno-suppressants, antilymphoma, antileukemic, antiviral and antiprotozoal agents.

Abstract: Novel xanthine compounds represented by the following formula: ##STR1## wherein each of R.sup.1, R.sup.2 and R.sup.3 independently represents hydrogen or lower alkyl;each of X.sup.1 and X.sup.2 independently represents oxygen or sulfur; and Q represents: ##STR2## The compounds are useful as a diuretic, a renal-protecting agent and bronchodilator.

Abstract: The present invention provides 8-substituted O.sup.6 -benzylguanines of the formula ##STR1## wherein R.sub.1, R.sub.2, and R.sub.3 are as defined in the specification, and 4(6)-substituted 2-amino-5-nitro-6(4)-benzyloxypyrimidine, and 4(6)-substituted 2-amino-5-nitroso-6(4)-benzyloxypyrimidine derivatives which have been found to be effective AGT inactivators, as well as pharmaceutical compositions comprising such derivatives along with a pharmaceutically acceptable carrier. The present invention further provides a method of enhancing the chemotherapeutic treatment of tumor cells in a mammal with an antineoplastic alkylating agent which causes cytotoxic lesions at the O.sup.6 -position of guanine, by administering to a mammal an effective amount of one of the aforesaid derivatives, 2,4-diamino-6-benzyloxy-s-triazine, 5-substituted 2,4-diamino-6-benzyloxypyrimidines, or 8-aza-O.sup.

Abstract: Novel pyrrolidine monomers bearing various functional groups are used to prepare oligomeric structures. The pyrrolidine monomers can be joined via standard phosphate linkages including phosphodiester and phosphorothioate linkages. Useful functional groups include nucleobases as well as polar groups, hydrophobic groups, ionic groups, aromatic groups and/or groups that participate in hydrogen-bonding.

Abstract: An improved method for the preparation of acyclic nucleotide analogues comprises first condensing a cyclic carbonate with a purine or pyrimidine base and then reacting the alkylated base with an activated phosphonate. Novel cyclic carbonates are employed to yield the desired phosphonylmethoxyalkyl nucleotide analogues.

Abstract: Novel lyxose derivatives which selectively inhibit adenosine kinase and methods of preparing these compounds are provided. These compounds are useful in treating certain conditions in vivo which may be ameliorated by increased local concentrations of adenosine.

Abstract: Methods of preventing or inhibiting ischemia-reperfusion injury in an organ by administration of a composition containing a selective A.sub.1 adenosine receptor antagonist are provided.

Abstract: A quinoline compound represented by the formula (1) or a salt thereof: ##STR1## wherein the definition of each substituents are described in the specification, which have angiotensin II antagonism and hypotensive action and are useful as an agent for the prevention and treatment of cardiovascular system diseases such as hypertension, heart failure and the like.

Abstract: R-(-)-1-(5-Hydroxyhexyl)-3-methyl-7-propylxanthine, a process for its preparation, and pharmaceuticals which contain this compound and which are suitable, in particular, for the prophylaxis and treatment of cerebral vascular disorders.

Abstract: There is disclosed compounds and pharmaceutical compositions comprising compounds of the formula: ##STR1## wherein each of one or two R is independently ##STR2## wherein n is an integer from 7 to 20, at least one of X or Y is --OH and if one of X or Y is --OH then the other X or Y is H, CH.sub.3, CH.sub.3 --CH.sub.2, CH.sub.3 --(CH.sub.2).sub.2 --, or (CH.sub.3).sub.2 --CH.sub.2 --, and W.sub.1, W.sub.2, and W.sub.3 is independently H, CH.sub.3, CH.sub.3 --CH.sub.2, CH.sub.3 --(CH.sub.2).sub.2 --, or (CH.sub.3).sub.2 --CH.sub.2 --, and wherein the alkyl groups may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom, H or alkyl (1-4C), including resolved enantiomers and/or diastereomers, salts and mixtures thereof. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells.

Abstract: A compound represented by the following formula I:(HET)Ar--X--CH.sub.2 --Y--CH.sub.2 --O--R (I)wherein:(HET)Ar represents a bicyclic hetero aryl nucleus which is unsubstituted or is substituted;X represents --S--;Y represents --CO--, --C.dbd.N--R.sub.2, in which R.sub.2 is hydrogen or a linear or branched alkyl having 1 to 10 carbon atoms, OH, an alkoxy having 1 to 10 carbon atoms, aryloxy, arylalkoxy, --NH.sub.2, --NHCONH.sub.2, --NHCSNH.sub.2 ; and R represents a phenyl substituted at para position with a carboxyl or a (C.sub.1 -C.sub.20) alkoxycarbonyl group in which the alkoxy group is linear or branched.

Abstract: The present invention provides sulfur-containing xanthine derivatives which are 1,3-disubstituted with a C.sub.1 -C.sub.12 alkyl, which may be further substituted with a hydroxy, amino, or halo group, and are 8-substituted with either a cycloalkyl, furyl, thienyl, or substituted phenyl group. These derivatives possess increased selectivity or potency at adenosine receptors.

Abstract: A novel xanthine derivative of the formula (I): ##STR1## wherein one of R.sup.1 and R.sup.2 represents substituted or unsubstituted lower alkyl, lower alkenyl, lower alkynyl, substituted or unsubstituted alicyclic alkyl, substituted or unsubstituted phenyl, or substituted or unsubstituted benzyl; and the other represents--(CH.sub.2).sub.m --Xwherein m is 2 or 3, and X is amino substituted phenyl.Q represents ##STR2## (wherein R.sup.3 and R.sup.4 are the same or different and are substituted or unsubstituted alicyclic alkyl), ##STR3## or a pharmacologically accetable salt thereof is disclosed. This derivative has anti-dementia activity.

Abstract: Adenosine and xanthine derivatives, and compositions comprising those compounds, are potent selective agonists and antagonists of adenosine receptors. The derivatives and composition are used to treat conditions, including certain cardiac arrhythmias.

Abstract: There is disclosed compounds and pharmaceutical compositions having a xanthine core of the formula: ##STR1## wherein each of one or two R is independently ##STR2## wherein n is an integer from about 3 to about 18 forming a hydrocarbon chain, wherein the hydrocarbon chain may have one or more double bonds (preferably in a cis configuration), and may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom. The compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.

Abstract: The invention relates to cyclic imino derivatives of general formula ##STR1## wherein A to G, R.sub.1, Z.sub.1 to Z.sub.6, X and Y are defined as in claim 1, the tautomers, stereoisomers and mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable pharmacological properties, preferably aggregation-inhibiting properties, pharmaceutical compositions which contain these compounds and processes for preparing them.

Abstract: Compounds of the formula ##STR1## wherein R.sub.1 is a substituted purinyl group including pharmaceutically acceptable salts are useful as antiviral agents.

Abstract: The use of xanthine derivatives for the treatment of secondary nerve cell damage and functional disorders after cranio-cerebral traumas (CCT)The use of xanthine derivatives of the formula I ##STR1## and of their physiologically tolerable salts, in which R.sup.1 is oxoalkyl, hydroxyalkyl or alkyl, R.sup.2 is hydrogen or alkyl and R.sup.3 is hydrogen, alkyl, oxoalkyl or an alkyl having up to 6 carbon atoms, whose carbon chain is interrupted by an oxygen atom, for the production of pharmaceuticals for the treatment of disorders which can occur after cranio-cerebral traumas is described.

Abstract: R-(-)-1-(5-Hydroxyhexyl)-3-methyl-7-propylxanthine, a process for its preparation, and pharmaceuticals which contain this compound and which are suitable, in particular, for the prophylaxis and treatment of cerebral vascular disorders.

Abstract: There is provided a novel xanthine Compound(I) ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and each represent hydroxy-substituted, oxo-substituted or unsubstituted lower alkyl, Y is a single bond or alkylene, and Q is ##STR2## wherein R.sup.3 and R.sup.4 are the same or different and each represent hydrogen or hydroxy, n is 0 or 1; provided that when both of R.sup.3 and R.sup.4 are hydrogen, at least one of R.sup.1 and R.sup.2 is hydroxy-substituted or oxo-substituted lower alkyl; or a pharmaceutically acceptable salt thereof.The xanthine compound has adenosine A.sub.1 receptor antagonizing activity, and thus shows diuretic effect, renal-protecting effect, bronchodilatory effect, cerebral function improving effect and anti-dementia effect.

Abstract: There are described 8-(1-aminocycloalkyl)-1,3-dialckylxantaine, their derivatives and their salts with adenosine antagonist activity. A process for the preparation of said compounds and pharmaceutical compositions containing them as antidepressant, nootropic and psychostimolant drugs are also described.

Abstract: There is disclosed compounds and pharmaceutical compositions having a xanthine core and one or two hydrocarbon side chains bonded to a ring nitrogen atom, wherein the hydrocarbon side chains are independently a straight chain hydrocarbon having at least one double bond in a carbon chain length of from about 4 to about 18 carbon atoms in length, wherein multiple double bonds are separated from each other by at least three carbon atoms, and wherein the hydrocarbon chain may be substituted by a hydroxyl, halo or dimethylamino group and/or interrupted by an oxygen atom. The compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.

Abstract: A xanthine derivative of the formula (I): ##STR1## wherein R.sup.1 and R.sup.2 are the same or different and are substituted or unsubstituted alicyclic alkyl; m1 and m2 are the same or different and represent an integer of 0 to 2; and Q represents ##STR2## (in which R.sup.3 and R.sup.4 are the same or different and are substituted or unsubstituted alicyclic alkyl) or ##STR3## (in which n is 0 or 1, and Y is a single bond or alkylene); or a pharmaceutically acceptable salt thereof is disclosed.This derivative has diuretic activity and renal protecting activity.

Abstract: Compounds, physiologically acceptable salts of the compounds and pharmaceutical compositions containing the compounds or the salts are provided wherein the compounds have a formula of: ##STR1## in which R.sub.1 is a C.sub.2 -C.sub.5 .omega.-hydroxy-n-alkyl group or a C.sub.3 -C.sub.5 (.omega.-1)-hydroxy-n-alkyl group, R.sub.3 is a C.sub.1-C.sub.4 alkyl group, R.sub.8 is H, methyl, or ethyl and the sum of the carbon atoms in R.sub.1 and R.sub.3 is between 4 and 9 and provide inotropic (cardiotonic) activity.

Abstract: Substituted Imidazo-fused 6-membered heterocycles of structural formula: ##STR1## wherein A, B, C, and D are independently carbon atoms or nitrogen atoms are angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure.

Abstract: A compound of formula (I): ##STR1## or where appropriate a pharmaceutically acceptable salt thereof, wherein R.sup.1 and R.sup.2 each independently represent a moiety of formula (a):--(CH.sub.2).sub.m --A (a)wherein m represents zero or an integer 1, 2 or 3, A represents a substituted or unsubstituted cyclic hydrocarbon radical; andR.sup.3 represents hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl or a moiety of formula (a) as defined above; a pharmaceutical composition comprising such a compound a process for preparing such a compound and the use of said compound and said composition in medicine.

Abstract: Xanthine derivatives having antiasthmatic activity are disclosed which have the following formula: ##STR1## where R is a linear or branched alkyl chain group of from one to six carbon atoms, R.sub.1 is a linear or branched alkyl or hydroxyalkyl group of from one to six carbon atoms. However, if R is methyl, then R.sub.1 is not methyl, ethyl or propyl; if R is ethyl, then R.sub.1 is not methyl or ethyl; and if R is methyl or n-butyl, then R.sub.1 is not 2-hydroxypropyl. Also disclosed are pharmaceutical compositions containing such xanthine derivatives.

Abstract: Irreversible ligands for adenosine receptors are derived from agonist and antagonist functionalized congeners which contain electrophilic acylating and alkylating groups for reaction at nucleophilic residues of adenosine receptors. The ligands are based on 8-aryl-substituted xanthines as antagonists and on N.sup.6 -substituted adenosine as agonists, wherein the electrophlic group may be, for example, isothiocyanate and N-hydroxysuccinimide esters.

Abstract: Compounds of the formula ##STR1## including the resolved enantiomers and/or diastereomers and mixtures thereof wherein each of one or two R is independently ##STR2## wherein n is 1-16 and R' is H or alkyl(1-4C); and wherein each remaining R is independently H, alkyl(1-6C), alkenyl(1-6C) or benzyl; an wherein said alkyl or alkenyl may be substituted by a hydroxyl, halo, or dimethylamino group, and/or interrupted by an oxygen atom, are useful in modulating the effects of internal and external stimuli on cells by reversing the effects of these stimuli on the short-term secondary messenger pathways. In particular, the compounds lower elevated levels of unsaturated, non-arachidonate phosphatidic acid (PA) and diacylglycerol (DAG) derived from said PA within seconds of the primary stimulus and their contact with said cells. The modulatory effect depends on the nature of the target cell and the stimulus applied.

Abstract: Antivirally active compounds of formula (I), wherein R.sup.1 is hydrogen, hydroxy, mercapto or amino; R.sup.2 is hydrogen, hydroxy, fluoro, chloro or amino; R.sup.3 and R.sup.4 are independently selected from (II), (III), amino, hydroxy or an ether or ester residue thereof, or R.sup.3 together with R.sup.4 is (IV), wherein M is hydrogen or a pharmaceutically acceptable counterion; and n is 1 or 2; with the proviso that, when R.sup.2 is amino and R.sup.3 and R.sup.4 are hydroxy R.sup.1 is not hydroxy and in addition, when n=1, R.sup.1 is not hydrogen, and pharmaceutically acceptable salts thereof; processes for preparation of said compounds, a pharmaceutical composition comprising said compounds, methods for treatments of virus infections as well as use of compounds of formula (I) without the proviso for the manufacture of a medicament for treatment of AIDS.

Abstract: Xanthines of the general formula: ##STR1## wherein R.sup.1 represents a straight or branched chain alkyl, alkenyl or alkynyl group of 3-6 carbon atoms, and R.sup.2 and R.sup.3, which may be the same or different, each represent hydrogen or halogen or a methyl, methoxy, nitro or trifluoromethyl group or R.sup.2 and R.sup.3 together form a methylenedioxy or ethylenedioxy group; with the proviso that R.sup.2 and R.sup.3 are not both hydrogen; and pharmacologically acceptable salts thereof with an alkali metal base or a nitrogen base containing organic base, are bronchodilators making them of value in treating asthma and vasodilators making them of interest in treating angina, hypertension, congestive heart failure and multi-infarct dementia. The compounds are also of use in combatting other conditions where inhibition of PDE type IV is thought to be beneficial.

Abstract: Hapten-biotin conjugates in which the hapten is linked with biotin via a spacer, which has 26 to 40 atoms in its chain and contains at least 5 heteroatoms, are novel and are suitable, in particular for use in a competitive homogeneous immunoassay in which the agglutination which occurs in the reaction is evaluated by turbidimetric or nephelometric measurements.

Abstract: Analogs of DNA containing sulfides, sulfoxides, and sulfones as linking groups between subunits capable of forming bonds with natural oligonucleotides are described. The analogs are lipophilic, stable to chemical degradation under a wide range of conditions and stable to enzymatic degradation in vivo.

Abstract: The invention is directed to a process for preparing 3,7-dialkylxanthines of the formula I ##STR1## (R.sup.1 and R.sup.2 denote C.sub.1 -C.sub.4 -alkyl) by the reaction of 4-amino-imidazolecarboxamide-(5) of the formula II ##STR2## with an alkali cyanate in aqueous solution at a pH of from 3 to 5 followed by cyclization of the resulting urea derivative at a pH of from 8 to 14.

Abstract: The present invention relates to certain novel 8-substituted purines as selective A.sub.1 -adenosine receptor antagonists which are useful in the treatment of patients suffering from Alzheimer's disease, congestive heart failure or pulmonary bronchoconstriction.

Abstract: The present invention relates to 6-substituted purine carbocyclic nucleosides and their use in medical therapy particularly in the treatment of HIV and HBV infections. The invention also relates to pharmaceutical formulations and processes for the preparation of compounds according to the invention.

Abstract: 1,3-Substituted-8-(oxo-substituted cycloalkyl)xanthines and pharmaceutically acceptable salts of such compounds are disclosed. Preferred compounds include the cis and trans isomers of 1,3-dipropyl-8-(3-hydroxycyclopentyl)xanthine and the cis and trans isomers of 1,3-dipropyl-8-(4-hydroxycyclohexyl)xanthine. The compounds are potent and selective bronchodilators and/or cardiotonic agents.

Abstract: A process for preparing 1,3-dipropyl-8-(3-oxocyclopentyl)-xanthine.

Abstract: Sulfonamides of the general formula I ##STR1## where R.sup.1 is hydrogen of C.sub.1 -C.sub.4 -alkyl,R.sup.2 is hydrogen or substituted or unsubstituted C.sub.1 -C.sub.6 -alkyl; C.sub.3 -C.sub.4 -alkenyl; C.sub.3 -C.sub.4 -alkynyl or substituted or unsubstituted saturated or singly unsaturated 5- to 7- membered heteroaryl;R.sup.3 and R.sup.4 are halogen; substituted or unsubstituted C.sub.1 -C.sub.4 -alkoxy C.sub.1 -C.sub.4 -alkylthio, C.sub.2 -C.sub.6 -alkenyl, C.sub.2 -C.sub.6 -alkenyloxy, C.sub.2 -C.sub.6 -alkenylthio, C.sub.2 -C.sub.6 -alkynyl, C.sub.2 -C.sub.6 -alkynyloxy, C.sub.2 -C.sub.6 -alkynylthio, C.sub.3 -C.sub.6 -cycloalkyl, C.sub.3 -C.sub.6 -cycloalkylthio, C.sub.5 -C.sub.6 -cycloalkenyl, C.sub.3 -C.sub.6 -cycloalkoxy, C.sub.5 -C.sub.6 -cycloalkenyloxy, C.sub.5 -C.sub.6 -cycloalkenylthio, phenyl, phenoxy, phenylthio, benzyl, benzyloxy or benzylthio;the group given for R.sup.2, or NR.sup.7 R.sup.8, where R.sup.7 and R.sup.8 are hydrogen, C.sub.1 -C.sub.6 -alkyl, C.sub.3 -C.sub.6 -alkenyl, C.sub.

Abstract: Fungicidal compounds of the formula (I): ##STR1## and stereoisomers thereof, wherein K is oxygen or sulphur; Z is optionally substituted aryl or optionally substituted heteroaryl; X is O, S(O).sub.n, NR.sup.4, CR.sup.1 R.sup.2, CHR.sup.5, CO, CR.sup.1 (OR.sup.2), C.dbd.CR.sup.1 R.sup.2, CHR.sup.1 CHR.sup.2, CR.sup.1 .dbd.CR.sup.2, CHR.sup.1 CR.sup.2 .dbd.CH, C.dbd.C, OCHR.sup.1, CHR.sup.1 O, OCHR.sup.1 O, S(O).sub.n CHR.sup.1, S(O).sub.n CHR.sup.1 O, CHR.sup.1 S(O).sub.n, CHR.sup.1 OSO.sub.2, NR.sup.4 CHR.sup.1, CHR.sup.1 NR.sup.4, CO.sub.2, O.sub.2 C, SO.sub.2 O, OSO.sub.2, CO.CO, COCHR.sup.1, COCHR.sup.1 O, CHR.sup.1 CO, CHOH.CHR.sup.1, CHR.sup.1.CHOH, ##STR2## CONR.sup.4, OCONR.sup.4, NR.sup.4 CO, CSNR.sup.4, OCS.NR.sup.4, SCO.NR.sup.4, NR.sup.4 CO.sub.2, NR.sup.4 CS, NR.sup.4 CSO, NR.sup.4 COS, NR.sup.4 CONR.sup.4, S(O).sub.n NR.sup.4, NR.sup.4 S(O).sub.n, CS.sub.2, S.sub.2 C, CO.S, SCO, N.dbd.N, N.dbd.CR.sup.1, CR.sup.1 .dbd.N, CHR.sup.1 CHR.sup.2 CH(OH), CHR.sup.1 OCO, CHR.sup.1 SCO, CHR.sup.1 NR.sup.

Abstract: Substituted Imidazo-fused 6-membered heterocycles of structural formula: ##STR1## wherein A, B, C, and D are independently carbon atoms or nitrogen atoms are angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure.

Abstract: Process for obtaining almost fluorescence-free xanthines by precipitation of xanthines which still contain an unsubstituted nitrogen atom in the molecule from aqueous-alkaline solution by means of CO.sub.2.

Abstract: A new piperidine compound is pharmacologically effective for treatment of arrythmia and has the formula: ##STR1## in which R.sup.1 is lower alkyl or tolyl; R.sup.2 is hydrogen, lower alkyl, lower alkenyl, cycloalkyl or cycloalkylalkyl; X is --CO--, --CH.sub.2 -- or --CHOH--; the sum of g plus h equals the integer 3 or 4 with g and h being 1, 2 or 3; A is substituted or unsubstituted alkylene, alkenylene, --(CH.sub.2).sub.k --S--, wherein k is an integer of 2 to 5, or --(CH.sub.2).sub.p CO--, wherein p is an integer of 1 to 4; and B is a compound having at least one heterocyclic ring containing a nitrogen atom.

Abstract: Therapeutic agents for the treatment of peptic ulcer disease, containing as active ingredient, at least one compound of the general formula I ##STR1## wherein one of R.sup.1 and R.sup.3 is ##STR2## (wherein m is 1-5, R.sup.4 represents a (C.sub.1 -C.sub.4)alkyl group); the other one of R.sup.1 and R.sup.3 is hydrogen, (C.sub.3 -C.sub.6)alkenyl or (C.sub.1 -C.sub.8)alkyl which can be substituted with up to 2 hydroxyl groups or a (C.sub.1 -C.sub.4)alkoxy group; and R.sup.2 is (C.sub.1 -C.sub.4)alkyl.

Abstract: Substituted Imidazo-fused 6-membered heterocycles of structural formula: ##STR1## wherein A, B, C, and D are independently carbon atoms or nitrogren atoms are angiotensin II antagonists useful in the treatment of hypertension and congestive heart failure.

Abstract: Adenosine analogues which act selectively at adenosine receptors and which act in general as adenosine antagonists are disclosed. From in vitro studies it is known that specific physiological effects can be distinguished as a result of this selectivity and that adenosine receptor activity in vitro correlates with adenosine receptor activity in vivo. Pharmaceutical preparations of the subject compounds can be prepared on the basis of the selective binding activity of the compounds disclosed herein which can be expected to enhance certain physiological effects while minimizing others, such as decreasing blood pressure without decreasing heart rate.

Abstract: Therapeutic agents for the treatment of peptic ulcer disease, containing as active ingredient, at least one compound of the general formula ##STR1## wherein R.sup.1 and R.sup.3 are the same or different and are each (C.sub.1 -C.sub.8)alkyl, ##STR2## R.sup.2 is (C.sub.1 -C.sub.4)alkyl; R.sup.4 and R.sup.5 are the same or different and are each hydrogen or (C.sub.1 -C.sub.2)alkyl; R.sup.6 is (C.sub.1 -C.sub.2)alkyl; and m, n and p are the same or different and are each 1, 2, 3, 4, 5 or 6; with the proviso that one of the groups R.sup.1 and R.sup.3 is ##STR3## or that R.sup.3 represents ##STR4## Some of the compounds of formula I are novel.

Abstract: This invention pertains to novel substituted N/aryl-N-[4-(1-heterocyclicalkyl)piperidinyl]amides useful as analgesics, and methods of administering analgesia, which comprises the systemic administration to mammals of such compounds, and pharmaceutical compositions containing such compounds, wherein the novel compounds have the general formula: ##STR1## including optically active isomeric forms, and the pharmaceutically acceptable acid addition salts thereof, wherein R, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are defined in the disclosure.