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: 2-(NB)-3-R-6-PY-5-Q-3H-imidazo[4,5-b]pyridines (I) and salts, useful as cardiotonics, where NB is amino or dimethylamino, R is lower-alkyl, Q is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, are prepared by reacting a 2-RNH-3-amino-5-PY-6-Q-pyridine with a di-(lower-alkyl) 2-methylthiopseudourea-1,3-dicarboxylate to produce 2-carbo(lower-alkoxy)amino-3-R-6-PY-5-Q-3H-imidazo[4,5-b] pyridine and hydrolyzing the latter to produce I where NB is amino and by reacting a 2-RNH-3-amino-5-PY-6-Q-pyridine with dichloromethylene-N,N-dimethylammonium chloride to produce I where NB is dimethylamino. Cardiotonic use of I is disclosed and claimed.

Abstract: Disclosed and claimed are a cardiac composition and a method for increasing cardiac contractility using an effective amount of a cardiotonic 4-[4-(or 3)-AcNH-phenyl]-2-R.sub.2 -3-R.sub.3 -5-R.sub.5 -6-R.sub.6 -pyridine (I) or pharmaceutically-acceptable salt thereof, where R.sub.2 is hydrogen, methyl, ethyl or hydroxyl, R.sub.6 is hydrogen, methyl or ethyl, R.sub.3 and R.sub.5 are each hydrogen or methyl, and Ac is hydrogen, hydroxyacetyl, acetoxyacetyl, .alpha.-hydroxypropionyl, .alpha.-acetoxypropionyl, methyoxyacetyl, 2-butenoyl or carbamyl or when NHAc is attached to the 4-position of the phenyl ring Ac also is formyl, n-propanoyl, 2,2-dimethyl-n-propanoyl or 3-carboxypropanoyl or when NHAc is attached to the 3-position of the phenyl ring Ac also is acetyl. Novel compounds shown and claimed are 4-[4-(or 3)-Ac'NH-phenyl]-2-R.sub.2 -3-R.sub.3 -5-R.sub.5 -6-R.sub.6 -pyridines (II) or pharmaceutically-acceptable acid-addition salts thereof, where R.sub.2, R.sub.3, R.sub.5 and R.sub.

Abstract: Disclosed and claimed are N-R-N-40 [4-(4-2-R.sub.2 -3-R.sub.3 -5-R.sub.5 -6-R.sub.6 -4-pyridinyl)phenyl]ureas (I) or pharmaceutically-acceptable acid-addition salts thereof, where R is hydrogen, methyl or ethyl, R.sub.2 is hydrogen, methyl, ethyl or hydroxyl, R.sub.6 hydrogen, methyl or ethyl, and R.sub.3 and R.sub.5 are each hydrogen or methyl, their cardiotonic use and their preparation.

Abstract: 1-R-3-R'-5-PY-1H-pyrazolo[3,4-b] pyridines (I) or acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a .alpha.-PY-.beta.dimethylamino-acrolein with 5-amino-1-R-3-R'-1H-pyrazole, where R is lower-alkyl or lower-hydroxyalkyl, R' is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. Also shown are cardiotonic compositions and method for increasing cardiac contractility using said compounds (I) or pharmaceutically acceptable acid-addition salts thereof.

Abstract: Shown is a process for preparing cardiotonically active 1,3-dihydro-3-R-6-PY-5-Q-2H-imidazo[4,5-b]pyridin-2-ones, where Q is hydrogen or lower-alkyl, R is lower-alkyl, lower-hydroxyalkyl, lower-alkoxyalkyl or Y-NB where Y is lower-alkylene and NB is di-(lower-alkyl)amino or 4-morpholinyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two substituents, by reacting a 2-RNH-5-PY-6-Q-nicotinamide with an alkali metal hypohalite. Also shown are cardiotonic compositions and a method for increasing cardiac contractility using 2-RR'N-5-PY-6-Q-nicotinamides or pharmaceutically acceptable acid-addition salts thereof, where R' is hydrogen or methyl. Also shown is the process for preparing said 2-RR'N-5-PY-6-Q-nicotinamides by reacting a 2-halo-5-PY-6-Q-nicotinamide with an amine of the formula RR'NH.

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: 1-R.sub.1 -3-[amino, cyano, carbamyl, halo, lower-alkylamino, di-(lower-alkyl)amino or lower-acylamino]-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones or pharmaceutically-acceptable acid-addition or cationic salts thereof are useful as cardiotonic agents, where R.sub.1 is hydrogen, lower-alkyl or lower-hydroxyalkyl. 1-R.sub.1 -3-amino-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones are prepared by hydrolyzing the corresponding 3-cyano compounds to produce the corresponding 3-carbamyl compounds and reacting the latter with a reagent capable of converting carbamyl to amino. The 1-R.sub.1 -3-cyano-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones are prepared by reacting (pyridinylmethyl) lower-alkyl ketones with dimethylformamide di-(lower-alkyl) acetal to produce 1-(pyridinyl)-2-(dimethylamino)ethenyl lower-alkyl ketone and reacting said ketones with N-R.sub.1 -o-cyanoacetamide to produce the 1-R.sub.1 -3-cyano-6-(lower-alkyl)-5-(pyridinyl)-2(1H)-pyridinones.

Abstract: 1-R.sub.1 -1,2-dihydro-6-[2-(dimethylamino)ethenyl]-2-oxo-5-PY-nicotinonitriles, where R.sub.1 is hydrogen or methyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, or pharmaceutically acceptable acid-addition salts thereof are useful as cardiotonic agents. Said compounds are prepared by reacting 1,2-dihydro-6-methyl-2-oxo-5-PY-nicotinonitrile with dimethylformamide dimethylacetal. Shown is the cardiotonic use of said compounds or pharmaceutically acceptable acid-addition salts thereof.

Abstract: N-acetyl-para-aminophenyl N'acetylaminothioalkanoates I are new analgesic compounds with greatly reduced hepatotoxic effects, when taken in overdose, relative to N-acetyl-para-aminophenol. They are prepared by reacting an N-acetylaminothioalkanoic acid IV with a reactive organic chloride V to form a mixed anhydride II and then reacting the latter with N-acetyl-para-aminophenol. The mixed anhydrides II are new and useful intermediates. Alternatively the derivatives I may be prepared by reacting the acid IV with bis-(4-nitrophenyl) sulfite to form a para-nitrophenyl N-acetylaminothioalkanoic acid ester VIII, reducing the latter to a para-aminophenyl-N-acetylaminothioalkanoate VII, and acetylating this product. The esters VII and VIII are new and useful intermediates. Both reactions may pass through S-blocked intermediates, which are also new. Pharmaceutical compositions containing the derivatives I are disclosed, and also analgesic methods using them.

Abstract: 1-R-3-(NB)-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridines or pharmaceutically-acceptable acid-addition salts thereof, which are useful as cardiotonics, are prepared by reacting a 1-R-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridin-3-amine with a lower-alkanoic acid and reducing agent to produce 1-R-3-(NB)-5-PY-6-Q-1H-pyrazolo[3,4-b]pyridine (I) where NB is NHR.sub.1 or NR.sub.1 R.sub.2, with a mixture of formic acid and formaldehyde to produce I where NB is N(CH.sub.3).sub.2 or with a lower-acylating agent to produce I where NB is NHAc and, if desired, reacting the 3-(NHAc) compound with a reducing agent to prepare the corresponding 3-NHR.sub.1 compound, where R is lower-alkyl, lower-hydroxyalkyl, lower-acyloxy-(lower-alkyl) or lower-alkoxy-alkyl, Q is hydrogen or lower-alkyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, and NB is selected from NHR.sub.1, NR.sub.1 R.sub.2 or NHAc where R.sub.1 and R.sub.2 are each lower-alkyl and Ac is lower-acyl.

Abstract: 3-(Hydroxy or hydroxymethyl)-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically acceptable acid-addition salt thereof is useful as a cardiotonic agent. 3-Hydroxy-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone is prepared by autoclaving a mixture of a sodium or potassium lower-alkoxide, a lower-alkanol and 3-(chloro or bromo)-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone and acidifying the reaction mixture. 3-Hydroxymethyl-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone is prepared by reacting 6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone with excess formaldehyde at an acidic pH. Said 3-(hydroxy or hydroxymethyl)-6-methyl-5-(4-pyridinyl)-2(1H)-pyridinone or pharmaceutically acceptable acid-addition salt thereof is disclosed as the active ingredient in cardiotonic compositions for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment.

Abstract: 3-Hydrazino-6-PY-pyridazine or pharmaceutically-acceptable acid-addition salt thereof is useful as a cardiotonic agent, where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents. 6-PY-3-pyridazinol is prepared by reacting 6-PY-3-pyridazinol with a chlorinating agent to produce 3-chloro-6-PY-pyridazine and reacting said 3-chloro compound with hydrazine to produce said 3-hydrazino compound. 3-Hydrazino-6-PY-pyridazine or pharmaceutically-acceptable acid-addition salt thereof is disclosed as the active component in cardiotonic compositions for increasing cardiac contractility and in the method for increasing cardiac contractility in a patient requiring such treatment. The novel intermediate 3-chloro-6-PY-pyridazine is prepared as noted above.

Abstract: 2-[R.sub.1 NHN(R)]-3-Q'-5-PY-6-Q-pyridines or pharmaceutically-acceptable acid-addition salts thereof are useful as cardiotonic agents, where Q is hydrogen or lower-alkyl, PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, Q' is hydrogen or halo, R is hydrogen, lower-alkyl or lower-hydroxyalkyl, and R.sub.1 is hydrogen or when R is other than hydrogen R.sub.1 is the same as R. These compounds are prepared by reacting a 2-halo-3-Q'-5-PY-6-Q-pyridine with R.sub.1 NHNHR where 2-halo is bromo or chloro. Also shown are: the use of said 2-[R.sub.1 NN(R)]-3-Q'-5-PY-6-Q-pyridines as cardiotonic agents; and, the intermediates, 2,3-dihalo-5-PY-6-Q-pyridines, and their preparation from 3-nitro-5-PY-6-Q-2(1H)-pyridinones.

Abstract: An improved method of preparing 3-(4-pyridinyl)aniline comprises heating 3-(4-pyridinyl)-2-cyclohexen-1-one oxime with an excess each of acetic anhydride and anhydrous phosphoric acid, distilling off the acetic acid by-product and excess acetic anhydride, adjusting the pH of the reaction mixture to about 5 to 9 with concentrated aqueous alkali, extracting N-acetyl-3-(4-pyridinyl)aniline from the concentrated aqueous phosphate salt solution with a lower-alkanol, and hydrolyzing the N-acetyl-3-(4-pyridinyl)aniline.

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: N-Hydroxy-1-R.sub.1 -1,2-dihydro-2-oxo-5-PY-6-R-nicotinimidamides or pharmaceutically-acceptable acid-addition salts thereof, useful as cardiotonic agents, are prepared by reacting 1-R.sub.1 -1,2-dihydro-2-oxo-5-PY-6-R-nicotinonitriles with hydroxylamine and are converted by reaction with polyphosphoric acid to the corresponding cardiotonically useful 1-R.sub.1 -3-amino-5-PY-6-R-2(1H)-pyridinones, where R.sub.1 is hydrogen, lower-alkyl and lower-hydroxyalkyl, R is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents.

Abstract: 2-R-4-R'-6-PY-3(2H)-pyridazinones (I) or salts thereof, which are useful as intermediates and some as cardiotonics, are prepared by reacting di-(lower-alkyl) hydroxy[2-oxo-2-PY-ethyl]propanedioate (II) with a hydrazine salt of the formula RNHNH.sub.2.nH.sub.x An (III) to produce lower-alkyl 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxylate (Ia where R' is lower-carbalkoxy) and reacting Ia with hydrazine hydrate or anhydrous hydrazine to produce 2,3-dihydro-2-R-3-oxo-6-PY-4-pyridazinecarboxylic acid hydrazide (Ib where R' is aminocarbamyl), where PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, R is hydrogen, lower-alkyl or lower-hydroxyalkyl, R' is carbamyl, carboxy, aminocarbamyl or lower-carbalkoxy, n is 1 or 2, x is 1, 2 or 3, and An is an anion of a strong inorganic acid or an organic sulfonic acid. Also shown are: the preparation of II from PY-COCH.sub.

Abstract: 2-R-4,5-dihydro-4-R'-6-PY-3(2H)-pyridazinones (I) or salts thereof, which are useful as cardiotonics, where R is lower-alkyl or lower-hydroxyalkyl, R' is hydrogen or lower-alkyl, and PY is 4- or 3-pyridinyl or 4- or 3-pyridinyl having one or two lower-alkyl substituents, are prepared by reacting 4-oxo-4-PY-2-R'-butanenitrile with an N-R-hydrazine salt of a strong inorganic acid or organic sulfonic acid or by reacting a lower-alkyl 4-oxo-4-PY-2-R'-butanoate or lower-alkyl 4-(BN)-4-cyano-4-PY-2-R'-butanoate with N-R-hydrazine where BN is 4-morpholinyl, 1-piperidinyl or 1-pyrrolidinyl. Also shown are: (a) cardiotonic compositions and a method for increasing cardiac contractility using said compounds or salts where R is lower-alkyl (b) the use of I as intermediates in preparing the corresponding 2-R-4-R'-6-PY-3(2H)-pyridazinones; and, (c) the preparation of said lower-alkyl 4-(BN)-4-cyano-4-PY-2-R'-butanoates.