Abstract: 3,4-Dihydro-3-R.sub.1 -4-R.sub.2 -5-Q-6-R-2(1H)-pyridinones (I), where R.sub.1 and R.sub.2 are each hydrogen or methyl, R is lower-alkyl, and Q is 4(or 3)-hydroxyphenyl, 4(or 3)-methoxyphenyl, 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents, or acid-addition salts thereof, and their preparation are shown. Also shown is the cardiotonic use of I where Q is 4(or 3)-hydroxyphenyl, 4(or 3)-pyridinyl or 4(or 3)-pyridinyl having one or two lower-alkyl substituents.

Abstract: 3-Methyl-4-(4-pyridinyl)benzeneamines, useful as cardiotonic agents, are prepared by reaction of pyridine, benzoyl chloride and an appropriate 3-methyl-N,N-di-lower-alkylbenzeneamine in the presence of copper powder and decomposing the reaction mixture with alkali and, if desired, reacting a resulting 3-methyl-4-(4-pyridinyl)-N,N-di-lower-alkylbenzeneamine with hydrogen bromide and pyridine to obtain 3-methyl-4-(4-pyridinyl)benzeneamine.

Abstract: 1-R"-3-Q-4-R'-5-R-1,6-naphthyridin-2(1H)-ones (I) or salts thereof, where R is lower-alkyl, R' is hydrogen or methyl, R" is hydrogen or lower-alkyl, and Q is hydrogen, hydroxy, amino, cyano, carbamyl, carboxy or aminocarbamyl, are useful as cardiotonic agents (I, Q is hydrogen, hydroxy, amino, cyano or carbamyl) and/or intermediates therefor (I, Q is carboxy, aminocarbamyl, hydrogen, amino, cyano or carbamyl). Also shown are 3-Q"-4-R'-5-(RCO)-6-[2-(di-lower-alkylamino)ethenyl]-2(1H)-pyridinones (II) or salts thereof, where R and R' are as above and Q' is hydrogen or cyano, which are useful as cardiotonics (II, Q' is hydrogen) and/or intermediates (II, Q' is cyano or hydrogen). Processes for preparing the compounds of formulas I and II are shown.

Abstract: The invention resides in a process for preparing cardiotonically active 1,2-dihydro-6-(lower-alkyl)-2-oxo-5-(pyridinyl)nicotinonitriles (III) which comprises reacting a pyridinylmethyl lower-alkyl ketone (I) with tri-(lower-alkyl) orthoformate, acetic anhydride and acetic acid to produce 2-(lower-alkoxy)-1-(pyridinyl)ethenyl lower-alkyl ketone (II) and then reacting II with malononitrile in a lower-alkanol, where pyridinyl is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents.

Abstract: 4-R.sub.2 -5-(Lower-alkanoyl)-6-(lower-alkyl)-2(1H)-pyridinones (I), useful as cardiotonics, where R.sub.2 is hydrogen or methyl, are prepared by reacting 2-(lower-alkanoyl)-1-(lower-alkyl)ethenamine (II) with lower-alkyl 2-propynoate or 2-butynoate respectively or by hydrolyzing 4-R.sub.2 -5-(lower-alkanoyl)-6-(lower-alkyl)-1,2-dihydro-2-oxonicotinonitrile (III, Q is CN) or corresponding 4-R.sub.2 -5-(lower-alkanoyl)-6-(lower-alkyl)-1,2-dihydro-2-oxonicotinamide to produce the corresponding 5-(lower-alkanoyl)-6-(lower-alkyl)-1,2-dihydro-2-oxonicotinic acid and decarboxylating said substituted nictotinic acid to produce I. Also disclosed and claimed are cardiotonic uses of 3-Q-4-R.sub.2 -5-(lower-alkanoyl)-6-(lower-alkyl)-2(1H)-pyridinones where Q is hydrogen or cyano and R.sub.2 is hydrogen or methyl (III). Also shown and claimed is methyl 4-acetyl-5-amino-2,4-hexadienoate or acid-addition salt thereof, useful as intermediate or cardiotonic.

Abstract: 5-PY-benzoxazol-2(3H)-ones, cardiotonic agents, are prepared by reacting 2-amino-4-PY-phenol with a carbonylating agent, e.g., carbonyldiimidazole, where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. 5-PY-benzoxazol-2(3H)-ones or pharmaceutically-acceptable acid-addition or cationic salts thereof are disclosed as active components in cardiotonic compositions for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment.

Abstract: A process for preparing cardiotonically active 1,2-dihydro-6-methyl-2-oxo-5-(pyridinyl)nicotinonitriles which comprises reacting a pyridinylmethyl methyl ketone with ethoxymethylenemalononitrile, where pyridinyl is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents.

Abstract: 4-Amino-2-R-6-PY-3(2H)-pyridazinones (I) or salts thereof, which are useful as cardiotonics, where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents are prepared by: (a) reaction of 2-R-6-PY-3(2H)-pyridazinone (II) with hydrazine; (b) conversion from 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxamide (III); or, (c) conversion form 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxylic acid hydrazide (IV). Also shown are: the use of I or salts as cardiotonic agents; and, the preparation of intermediates.

Abstract: 5-(Py-Y)-1H-benzimidazol-2-ol or 5-(Py-Y)-1H-benzimidazole-2-thiol or lower-alkyl ethers or thioethers thereof or pharmaceutically-acceptable acid-addition salts thereof, useful as cardiotonics, are prepared by reacting 4-(Py-Y)-1,2-benzenediamine with urear or carbonyldiimidazole to produce 5-(Py-Y)-1H-benzimidazol-2-ol or with thiourea, an alkali metal lower-alkyl xanthate or thiocarbonyldiimidazole to produce 5-(Py-Y)-1H-benzimidazole-2-thiol and by reacting 5-(Py-Y)-1H-benzimidazole-2-thiol with a lower-alkylating agent to produce 2-(lower-alkylthio)-5-(Py-Y)-1H-benzimidazole. 2-(Lower-alkoxy)-5-(Py-Y)-1H-benzimidazole is prepared by reacting 4-(Py-Y)-1,2-benzenediamine with tetra-(lower-alkoxy)methane.

Abstract: 2-R-5-(Py-Y)-1H-benzimidazole or pharmaceutically-acceptable acid-addition salt thereof, useful as a cardiotonic, is prepared by reacting 4-(Py-Y)-1,2-benzenediamine with a tri-(lower-alkyl)ortho-(lower-alkanoate) of the formula R--C(OR.sub.1).sub.3, where R is hydrogen or lower-alkyl, Y is a direct linkage or lower-alkylene having one or two carbon atoms, and Py is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, or with dimethylformamide dimethyl acetal or dimethylacetamide dimethyl acetal to produce said 2-R-5-(Py-Y)-1H-benzimidazole where R is methyl or ethyl respectively. The same compound where R is lower-alkyl is prepared in two steps by first reacting 4-(Py-Y)-1,2-benzenediamine with an alkanoylating agent providing alkanoyl of the formula ##STR1## to produce N.sub.2 --[R'--C(.dbd.O)]-4-(Py-Y)-1,2-benzenediamine and heating the latter compound to produce said 2-R'-5-(Py-Y)-1H-benzimidazole, where R' is lower-alkyl.

Abstract: 5-PY-benzoxazol-2(3H)-ones, cardiotonic agents, are prepared by reacting 2-amino-4-PY-phenol with a carbonylating agent, e.g., carbonyldiimidazole, where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. 5-PY-benzoxazol-2(3H)-ones or pharmaceutically-acceptable acid-addition or cationic salts thereof are disclosed as active components in cardiotonic compositions for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment.

Abstract: 4-Amino-2-R-6-PY-3(2H)-pyridazinones (I) or salts thereof, which are useful as cardiotonics, where R is hydrogen, lower-alkyl or lower-hydroxyalkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents are prepared by: (a) reaction of 2-R-6-PY-3(2H)-pyridazinone (II) with hydrazine; (b) conversion from 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxamide (III); or, (c) conversion form 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxylic acid hydrazide (IV). Also shown are: the use of I or salts as cardiotonic agents; and, the preparation of intermediates.

Abstract: 4(or 3)-(3,4-Dihydroxyphenyl)pyridine, a cardiotonic agent, is prepared by demethylating 4(or 3)-(3,4-dimethoxyphenyl)pyridine, preferably by heating with aqueous hydrogen bromide. 4(or3)-[3,4-di-(OR)-phenyl]pyridine, where R is hydrogen or methyl, or pharmaceutically-acceptable acid-addition salt thereof is disclosed as the active component in a cardiotonic composition for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment. The novel isomeric 2-[3,4-di-(OR)-phenyl]pyridine, where R is hydrogen or methyl, is shown for comparative purposes.

Abstract: 2-Amino-3(4 or 5)-PY-phenol, a cardiotonic agent, is prepared by reducing 2-nitro-3(4 or 5)-PY-phenol, where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. 2-Amino-3(4 or 5)-PY-phenol or pharmaceutically-acceptable acid-addition salt thereof is disclosed as the active component in a cardiotonic composition for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment. The novel isomeric 4-amino-5-(4-pyridinyl)phenol is shown for comparative purposes.

Abstract: 4-(3,4-Diaminophenyl)pyridine, a cardiotonic agent, is prepared by reducing 4-(4-amino-3-nitrophenyl)pyridine or preferably by reacting 4-(4-acetylamino-3-nitrophenyl)pyridine or 4-(3-acetylamino-4-nitrophenyl)pyridine with stannous chloride and hydrochloric acid. 4-(3,4-diaminophenyl)pyridine or pharmaceutically-acceptable acid-addition salt thereof is disclosed as the active ingredient in a cardiotonic composition for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment.

Abstract: Compounds useful as anti-allergic agents are 2-Q-4-[XZC.dbd.C(R)NH]-5-R.sub.1 -6-R.sub.2 -pyrimidines (I), where Q is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents or N-oxide thereof, R is hydrogen or lower-alkyl, R.sub.1 is hydrogen, lower-alkyl or cyano, R.sub.2 is hydrogen, lower-alkyl, hydroxy or halo, X and Z are the same or different and are each selected from lower-carbalkoxy, lower-alkanoyl, carbamyl and cyano, or ##STR1## is ##STR2## where R.sub.3 and R.sub.4 are each lower-alkyl, or X is hydrogen, are prepared by reacting 4-amino-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidine (II where Q' is amino) with R'O--C(R).dbd.CXZ (III). Preparations of II are given. Also shown as intermediates and/or anti-allergic agents are 4-(AcNH)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (IV) and 4-(R.sub.5 R.sub.6 N)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (V) where Ac is lower-alkanoyl or lower-carbalkoxy, R.sub.5 is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R.sub.

Abstract: The process of reacting a PY-carboxamidine with .alpha.-chloroacrylonitrile in the presence of an acid-acceptor to produce 2-PY-4-pyrimidinamines where PY is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents. The products produced by the process are useful as anti-allergic agents per se and, also, are useful as intermediates in the preparation of other anti-allergic agents, namely, dialkyl N-(2-PY-4-pyrimidinyl)-aminomethylenemalonates and analogs, as well as N-(2-PY-4-pyrimidinyl)ureas.

Abstract: Compounds useful as anti-allergic agents are 2-Q-4-[XZC=C(R)NH]-5-R.sub.1 -6-R.sub.2 -pyrimidines (I), where Q is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents or N-oxide thereof, R is hydrogen or lower-alkyl, R.sub.1 is hydrogen, lower-alkyl or cyano, R.sub.2 is hydrogen, lower-alkyl, hydroxy or halo, X and Z are the same or different and are each selected from lower-carbalkoxy, lower-alkanoyl, carbamyl and cyano, or ##STR1## is ##STR2## wherein R.sub.3 and R.sub.4 are each lower-alkyl, or X is hydrogen, are prepared by reacting 4-amino-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidine (II where Q' is amino) with R'O-C(R)=CXZ (III). Preparations of II are given. Also shown as intermediates and/or anti-allergic agents are 4-(AcNH)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (IV) and 4-(R.sub.5 R.sub.6 N)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (V) where Ac is lower-alkanoyl or lower-carbalkoxy, R.sub.5 is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R.sub.

Abstract: N--R.sub.3 --N--R.sub.4 --N'--(2--Q--5--R.sub.1 --6--R.sub.2 --4-Pyrimidinyl)ureas which are useful as anti-allergic agents are prepared by reacting a 2--Q--4--RNH--5--R.sub.1 --6--R.sub.2 -pyrimidine with an R.sub.4 '-isocyanate and reacting the intermediate product with 1,1'-carbonyldiimidasole.

Abstract: Compounds useful as anti-allergic agents are 2-Q-4-[XZC.dbd.C(R)NH]-5-R.sub.1 -6-R.sub.2 -pyrimidines (I), where Q is 4- or 3- or 2-pyridinyl or 4- or 3- or 2-pyridinyl having one or two lower-alkyl substituents or N-oxide thereof, R is hydrogen or lower-alkyl, R.sub.1 is hydrogen, lower-alkyl or cyano, R.sub.2 is hydrogen, lower-alkyl, hydroxy or halo, X and Z are the same or different and are each selected from lower-carbalkoxy, lower-alkanoyl, carbamyl and cyano, or ##STR1## is ##STR2## where R.sub.3 and R.sub.4 are each lower-alkyl, or X is hydrogen, are prepared by reacting 4-amino-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidine (II where Q' is amino) with R'O--C(R).dbd.CXZ (III). Preparation of II are given. Also shown as intermediates and/or anti-allergic agents are 4-(AcNH)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (IV) and 4-(R.sub.5 R.sub.6 N)-2-Q-5-R.sub.1 -6-R.sub.2 -pyrimidines (V) where Ac is lower-alkanoyl or lower-carbalkoxy, R.sub.5 is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R.sub.