- De novo Design of SARS-CoV-2 Main Protease Inhibitors
-
The COVID-19 pandemic prompted many scientists to investigate remedies against SARS-CoV-2 and related viruses that are likely to appear in the future. As the main protease of the virus, M Pro, is highly conserved among coronaviruses, it has emerged as a prime target for developing inhibitors. Using a combination of virtual screening and molecular modeling, we identified small molecules that were easily accessible and could be quickly diversified. Biochemical assays confirmed a class of pyridones as low micromolar noncovalent inhibitors of the viral main protease.
- Dovala, Dustin,Fischer, Christian,Nomura, Daniel K.,Peitsinis, Zisis,Spradlin, Jessica N.,Trauner, Dirk,Yang, Chao,Zhang, Yingkai,Rühmann, Klaus-Peter,Vep?ek, Nynke A.
-
supporting information
(2021/10/16)
-
- A new method using 1,3,5-triazine as an umpolung hydrogen cyanide equivalent toward the syntheses of isoquinolinone and 2-pyridone derivatives
-
An investigation of Hermecz and Hartenstein's cyclization methods was conducted. Overcoming the limited substrate scope allowed the expansion of the synthetic application of 1,3,5-triazine as an umpolung hydrogen cyanide equivalent. The reaction proceeded under mild conditions to provide various isoquinolinone and 2-pyridone derivatives with excellent yields.
- Hayashida, Joji,Yoshida, Shinya
-
supporting information
p. 3876 - 3879
(2018/10/02)
-
- MODIFIED COMPOUND OF ANDROGRAPHOLIDE
-
The present disclosure discloses a modified compound of andrographolide, and particularly discloses a compound shown in formula (I) and (II) or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0523-0525
(2019/01/04)
-
- Preparation method of 2-chloro-5-cyano nitrogen-containing six-membered heterocyclic compound
-
The invention provides a preparation method of a 2-chloro-5-cyano nitrogen-containing six-membered heterocyclic compound. The method comprises the following steps: using a 2-hydroxy-5-bromine nitrogen-containing six-membered heterocyclic compound as a raw material, under existence of a catalyst, in atmosphere of carbon monoxide gas, using methanol as a solvent, and performing a coupling reaction to obtain a methyl 2-hydroxyl nitrogen-containing six-membered heterocyclic ring-5-carboxylate, and sequentially performing an aminolysis reaction, a chlorination reaction with phosphorus oxychloride,and an oxidation reaction to obtain the 2-chloro-5-cyano nitrogen-containing six-membered heterocyclic compound. The preparation method has the advantages of short route and easily available raw material, a post-processing method is simple, no column chromatography is required after each reaction, the reaction product can be purified only by washing and extraction of a solvent, amplification is realized, industrial production is carried out, the method accords with environmental protection requirements, and has important value for actual production.
- -
-
Paragraph 0069; 0070; 0071; 0072
(2019/01/08)
-
- Synthesis of a series of iridium complexes bearing substituted 2-pyridonates and their catalytic performance for acceptorless dehydrogenation of alcohols under neutral conditions
-
A series of Cp*Ir complexes bearing 5- and 4,5-substituted 2-pyridonate ligands have been synthesized and their catalytic performance for acceptorless dehydrogenation of alcohols has been investigated under neutral conditions. Electron-withdrawing groups such as methoxycarbonyl, trifluoromethyl, cyano, and nitro groups at the 5-position promoted the acceptorless dehydrogenation of 1-phenylethanol, whereas electron-donating methyl group at the 5-position retarded the reaction. Furthermore, introduction of methyl group at the 4-position improved the catalytic performance. Thus, Cp*Ir(5-trifluoromethyl-4-methyl-2-pyridonate)Cl (2bc) exhibited the highest catalytic performance among the complexes examined, and also showed good catalytic performance for acceptorless dehydrogenation of primary alcohols.
- Yamaguchi, Ryohei,Kobayashi, Daiki,Shimizu, Mineyuki,Fujita, Ken-ichi
-
supporting information
p. 14 - 19
(2017/05/19)
-
- PYRAZOLYL-SUBSTITUTED PYRIDONE COMPOUNDS AS SERINE PROTEASE INHIBITORS
-
There are provided inter alia pyrazolyl-substituted pyridone compounds, which exhibit biological activity, e.g., inhibitory action, against serine proteases, including thrombin and various kallikreins. There are additionally provided pharmaceutical compositions. There are additionally provided methods of treating and preventing certain diseases or disorders, which disease or disorder is amenable to treatment or prevention by the inhibition of serine proteases, including thrombin and various kallikreins.
- -
-
Paragraph 00399-00400
(2016/04/09)
-
- NOVEL ANTIFUNGAL OXODIHYDROPYRIDINECARBOHYDRAZIDE DERIVATIVE
-
The present invention relates to novel oxodihydropyridinecarbohydrazide derivatives with excellent antifungal activities, an antifungal composition containing the same, and its use for the prevention and treatment of fungal infectious diseases. The oxodihydropyridinecarbohydrazide derivatives of the present invention have excellent antifungal and fungicidal activities, and thus will be useful for the prevention and treatment of various fungal infections by Candida spp., Aspergillus spp., Cryptococcus neoformans and Trichophyton spp., etc. Additionally, the oxodihydropyridinecarbohydrazide derivatives of the present invention, unlike other fungicidal preparations, can be orally administered.
- -
-
Paragraph 440; 441
(2015/05/06)
-
- Indazole-and indole-5-carboxamides: Selective and reversible monoamine oxidase B inhibitors with subnanomolar potency
-
Indazole-and indole-carboxamides were discovered as highly potent, selective, competitive, and reversible inhibitors of monoamine oxidase B (MAO-B). The compounds are easily accessible by standard synthetic procedures with high overall yields. The most potent derivatives were N-(3,4- dichlorophenyl)-1-methyl-1H-indazole-5-carboxamide (38a, PSB-1491, IC 50 human MAO-B 0.386 nM, >25000-fold selective versus MAO-A) and N-(3,4-dichlorophenyl)-1H-indole-5-carboxamide (53, PSB-1410, IC50 human MAO-B 0.227 nM, >5700-fold selective versus MAO-A). Replacement of the carboxamide linker with a methanimine spacer leading to (E)-N-(3,4- dichlorophenyl)-1-(1H-indazol-5-yl)methanimine (58) represents a further novel class of highly potent and selective MAO-B inhibitors (IC50 human MAO-B 0.612 nM, >16000-fold selective versus MAO-A). In N-(3,4- difluorophenyl-1H-indazole-5-carboxamide (30, PSB-1434, IC50 human MAO-B 1.59 nM, selectivity versus MAO-A >6000-fold), high potency and selectivity are optimally combined with superior physicochemical properties. Computational docking studies provided insights into the inhibitors' interaction with the enzyme binding site and a rationale for their high potency despite their small molecular size.
- Tzvetkov, Nikolay T.,Hinz, Sonja,Küppers, Petra,Gastreich, Marcus,Müller, Christa E.
-
supporting information
p. 6679 - 6703
(2014/11/07)
-
- Neonicotinic analogues: Selective antagonists for α4β2 nicotinic acetylcholine receptors
-
Nicotine is an agonist of nicotinic acetylcholine receptors (nAChRs) that has been extensively used as a template for the synthesis of α4β2-preferring nAChRs. Here, we used the N-methyl-pyrrolidine moiety of nicotine to design and synthesise novel α4β2-preferring neonicotinic ligands. We increased the distance between the basic nitrogen and aromatic group of nicotine by introducing an ester functionality that also mimics acetylcholine (Fig. 2). Additionally, we introduced a benzyloxy group linked to the benzoyl moiety. Although the neonicotinic compounds fully inhibited binding of both [α-125I]bungarotoxin to human α7 nAChRs and [3H]cytisine to human α4β2 nAChRs, they were markedly more potent at displacing radioligand binding to human α4β2 nAChRs than to α7 nAChRs. Functional assays showed that the neonicotinic compounds behave as antagonists at α4β2 and α4β2α5 nAChRs. Substitutions on the aromatic ring of the compounds produced compounds that displayed marked selectivity for α4β2 or α4β2α5 nAChRs. Docking of the compounds on homology models of the agonist binding site at the α4/β2 subunit interfaces of α4β2 nAChRs suggested the compounds inhibit function of this nAChR type by binding the agonist binding site.
- Faundez-Parraguez, Manuel,Farias-Rabelo, Nicolas,Gonzalez-Gutierrez, Juan Pablo,Etcheverry-Berrios, Alvaro,Alzate-Morales, Jans,Adasme-Carre?o, Francisco,Varas, Rodrigo,Bermudez, Isabel,Iturriaga-Vasquez, Patricio
-
p. 2687 - 2694
(2013/06/27)
-
- Development of a safe and economical synthesis of methyl 6-chloro-5-(trifluoromethyl)nicotinate: Trifluoromethylation on kilogram scale
-
Reported herein is a safe and economical synthesis of methyl 6-chloro-5-(trifluoromethyl)nicotinate, an intermediate in the synthesis of novel anti-infective agents. The key to this process is the trifluoromethylation of an aryl iodide using an inexpensive methyl chlorodifluoroacetate (MCDFA)/KF/CuI system, with an emphasis on the development work which led to this effective process.
- Mulder, Jason A.,Frutos, Rogelio P.,Patel, Nitinchandra D.,Qu, Bo,Sun, Xiufeng,Tampone, Thomas G.,Gao, Joe,Sarvestani, Max,Eriksson, Magnus C.,Haddad, Nizar,Shen, Sherry,Song, Jinhua J.,Senanayake, Chris H.
-
p. 940 - 945
(2013/07/26)
-
- SUBSTITUTED N-ARYL PYRIDINONES
-
Disclosed herein are methods of administering deuterated pirfenidone and kits thereof.
- -
-
Page/Page column 62-63
(2012/09/22)
-
- PROCESS FOR THE PREPARATION OF NICOTINAMIDE DERIVATIVES
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The present invention relates to a process for the preparation of nicotinamide derivatives of the formula (I) R1 to R7 are as defined in the and to pharmaceutically acceptable salts thereof. The compounds of formula (I) are useful for the treatment and / or prophylaxis of diseases which are associated with the modulation of cannabinoid 1 receptors (CB 1 receptors) as described in the PCT Publ. WO 2006/106054.
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-
Page/Page column 12
(2012/05/05)
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- PROCESS FOR THE PREPARATION OF NICOTINAMIDE DERIVATIVES
-
The present invention relates to a process for the preparation of nicotinamide derivatives of formula I, wherein R1 to R7 are as defined above and to pharmaceutically acceptable salts thereof. The compounds of formula I are useful for the treatment and/or prophylaxis of diseases which are associated with the modulation of cannabinoid 1 receptors (CB1 receptors) as described in the PCT Publ. WO 2006/106054.
- -
-
Page/Page column 6
(2012/05/04)
-
- Inhibition of chorismate-utilising enzymes by 2-amino-4-carboxypyridine and 4-carboxypyridone and 5-carboxypyridone analogues
-
Several 2-amino-4-carboxypyridine, 4- and 5-carboxypyridone-based compounds were prepared and tested against three members of the chorismate-utilising enzyme family, anthranilate synthase, isochorismate synthase and salicylate synthase. Most compounds exhibited low micromolar inhibition of these three enzymes. The most potent inhibitor was a 4-carboxypyridone analogue bearing a lactate side chain on the pyridyl nitrogen which exhibited inhibition constants of 5, 91 and 54 μM against anthranilate synthase, isochorismate synthase and salicylate synthase respectively. The Royal Society of Chemistry 2010.
- Payne, Richard J.,Bulloch, Esther M. M.,Kerbarh, Olivier,Abell, Chris
-
experimental part
p. 3534 - 3542
(2010/08/21)
-
- Heteroaromatic tosylates as electrophiles in regioselective Mizoroki-Heck-coupling reactions with electron-rich olefins
-
Heteroaromatic 2-pyridyl tosylates were successfully applied as electrophiles in palladium(0)-catalyzed Mizoroki-Heck-coupling reactions to electron-rich olefins with complete aregioselectivity. This protocol represents a general strategy for the application of pyridyl tosylates and mesylates in the Mizoroki-Heck coupling. The catalytic system also proved adaptable to changes in the heteroaromatic core as well as large-scale applications. Finally, the synthetic utility of the functionalized α-heteroarylvinyl amides was established providing straightforward access to highly functionalized heteroaromatic compounds including chiral benzylic amide derivatives.
- Gogsig, Thomas M.,Lindhardt, Anders T.,Dekhane, Mouloud,Grouleff, Julie,Skrydstrup, Troels
-
supporting information; experimental part
p. 5950 - 5955
(2010/02/28)
-
- HETEROCYCLIC UREA DERIVATIVES AND METHODS OF USE THEREOF-211
-
Chemical Compounds Compounds of formula (I) and their pharmaceutically acceptable salts are described. Processes for their preparation, pharmaceutical compositions containing them, their use as medicaments and their use in the treatment of bacterial infections are also described.
- -
-
Page/Page column 296
(2009/10/21)
-
- SUBSTITUTED N-ARYL PYRIDINONES
-
Disclosed herein are substituted N-Aryl pyridinone fibrotic inhibitors and/or collagen infiltration modulators of Formula I, process of preparation thereof, pharmaceutical compositions thereof, and methods of use thereof.
- -
-
Page/Page column 22
(2009/01/24)
-
- N-SUBSTITUTED PYRIDINONE OR PYRIMIDINONE COMPOUNDS USEFUL AS SOLUBLE EPOXIDE HYDROLASE INHIBITORS
-
Disclosed are compounds of the formula (I) with the definitions of A1 D, Q, W, X, Y and Z as indicated in the description, which are active against soluble epoxide hydrolase (sEH), compositions thereof and methods of using and making same. (I)
- -
-
Page/Page column 31; 35
(2010/11/27)
-
- NOVEL HETEROARYL DERIVATIVE
-
A heteroaryl derivative of the formula (1): (wherein Ring Z is an optionally substituted heteroaryl, R1 is a carboxyl group or an alkoxycarbonyl group, etc., W1 and W2 are an optionally substituted lower alkylene, Ar1 is an optionally substituted arylene or an optionally substituted heteroarylene, W3 is a single bond, a lower alkylene, a lower alkenylene, etc., W4 is a single bond, -NR10-, etc., Ar2 is an optionally substituted aryl or an optionally substituted heteroaryl), or a prodrug thereof, or a pharmaceutically acceptable salt thereof.
- -
-
Page/Page column 52
(2008/06/13)
-
- Discovery of N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5- carboxamide, an agonist of the α7 nicotinic acetylcholine receptor, for the potential treatment of cognitive deficits in schizophrenia: Synthesis and structure-activity relationship
-
N-[(3R)-1-Azabicyclo[2.2.2]oct-3-yl]furo[2,3-c]pyridine-5-carboxamide (14, PHA-543,613), a novel agonist of the α7 neuronal nicotinic acetylcholine receptor (α7 nAChR), has been identified as a potential treatment of cognitive deficits in schizophrenia. Compound 14 is a potent and selective a7 nAChR agonist with an excellent in vitro profile. The compound is characterized by rapid brain penetration and high oral bioavailability in rat and demonstrates in vivo efficacy in auditory sensory gating and, in an in vivo model to assess cognitive performance, novel object recognition.
- Wishka, Donn G.,Walker, Daniel P.,Yates, Karen M.,Reitz, Steven C.,Jia, Shaojuan,Myers, Jason K.,Olson, Kirk L.,Jacobsen, E. Jon,Wolfe, Mark L.,Groppi, Vincent E.,Hanchar, Alexander J.,Thornburgh, Bruce A.,Cortes-Burgos, Luz A.,Wong, Erik H. F.,Staton, Brian A.,Raub, Thomas J.,Higdon, Nicole R.,Wall, Theron M.,Hurst, Raymond S.,Walters, Rodney R.,Hoffmann, William E.,Hajos, Mihaly,Franklin, Stanley,Carey, Galen,Gold, Lisa H.,Cook, Karen K.,Sands, Steven B.,Zhao, Sabrina X.,Soglia, John R.,Kalgutkar, Amit S.,Arneric, Stephen P.,Rogers, Bruce N.
-
p. 4425 - 4436
(2007/10/03)
-
- Unsaturated derivatives at the 4-position of 6-tert-butyl-1,1-dimethylindane and their use in human and veterinary medicine and cosmetics
-
6-tert-Butyl-1,1-dimethylindane derivatives which are unsaturated in the 4-position of formula: X represents: (i) either a radical of formula: (a) ?and Y represents a radical of formula: (b) (ii) or a radical of formula: (c) ?and Y represents either a radical of formula (b) or a radical of formula: Z being —O—, —S— or R1represents —CH3, —(CH2)p—OR4, —(CH2)p—COR5or —S(O)t—R6, p being 0, 1, 2 or 3, t being 0, 1 or 2, R2represents H or lower alkyl, R3represents H, lower alkyl or —COR7, R4represents H, lower alkyl, —COR7, aryl, aralkyl, mono- or polyhydroxyalkyl, or a polyether radical, R5represents H, lower alkyl, —OR8or —N(r′)(r″), R6represents H or lower alkyl, R7represents lower alkyl, R8represents H, alkyl, alkenyl, alkynyl, aryl, aralkyl, mono- or polyhydroxyalkyl, a sugar residue or an amino acid residue, r′ and r″ represent H, lower alkyl, —COR7, aryl, a sugar residue or an amino acid residue or r′ and r″ form a heterocycle, and the salts of the compounds of formula (I). Use in the topical and systemic treatment of dermatological conditions, as well as in cosmetics.
- -
-
-
- Antidiabetic agents
-
The present invention provides compounds of Formula (I): wherein A, X, Q, Y, B, D, Z, and E have any of the values defined in the specification, and pharmaceutically acceptable salt thereof, that are useful as antidiabetic agents. Also disclosed are pharmaceutical compositions comprising one or more compounds of Formula I, processes for preparing compounds of Formula I, and intermediates useful for preparing compounds of Formula I.
- -
-
-
- ENZYME DETECTION/ASSAY METHOD AND SUBSTRATES
-
The invention relates to a method of detecting and/or assaying nucleoside hydrolases or nucleoside phosphorylases using a chromogenic substrate. Preferred chromogenic substrates have formula (I) where X is OH, or H, and Y is the residue of Y—OH where Y—OH is a chromophore or a compound readily converted to a chromophore and the substrates are hydrolysed by the nucleoside hydrolase to yield ribose or 2-deoxyribose plus Y—OH. Alternatively those substrates may be phosphorylysed by nucleoside phosphorylase to yield ribose-1-phosphate plus Y—OH. The methods may be used to detect and/or assay parasites in biological samples.
- -
-
-
- Identification of alkylidene hydrazides as glucagon receptor antagonists
-
High throughput screening of our small molecule combinatorial library identified a class of benzoylnaphthalenehydrazones with modest affinity for the human glucagon receptor. Optimization of this initial hit through a series of targeted libraries and traditional medicinal chemistry led to ligands with nanomolar affinities. Pharmacological evaluation demonstrated that these ligands were competitive glucagon receptor antagonists. Intravenous administration of a representative benzoylnaphthalenehydrazone into rats attenuated glucagon-stimulated glucose levels.
- Ling,Hong,Gonzalez,Gregor,Polinsky,Kuki,Shi,Teston,Murphy,Porter,Kiel,Lakis,Anderes,May,Knudsen,Lau
-
p. 3141 - 3149
(2007/10/03)
-
- A highly efficient multicomponent synthesis of pyridones and pyrimidones by a [2+2+2] strategy
-
The reaction of N-silylated iminoethers with 2-substituted acetyl chlorides yields activated 2-azadienes. These were shown to react with electron-deficient acetylenic dienophiles to yield pyridones. They also react with quinones to give the corresponding aromatized cycloadducts in good yields. The reaction of 2-azadienes with activated nitriles provided a very practical route towards polysubstituted pyrimidones. A multicomponent protocol is reported which combines a N-t-butyldimethylsilyl iminoether, an acetyl chloride derivative and a dienophile in the presence of triethylamine without isolation of any intermediate. This provides an extremely practical and versatile route to various mono- and polycyclic azaaromatics with a predictable substitution pattern. Yields ranged from 43% to 94% for the complete sequence.
- Ghosez, Leon,Jnoff, Eric,Bayard, Philippe,Sainte, Francy,Beaudegnies, Renaud
-
p. 3387 - 3400
(2007/10/03)
-
- New synthetic amino acids for the design and synthesis of peptide-based metal ion sensors
-
The syntheses of two new nonstandard amino acids, Flu (6) and XBp (20), and a new synthesis of Dmd (12) are reported. These residues exhibit fluorescence, metal-coordination, and fluorescence-quenching properties, respectively. These building blocks have been incorporated into peptides via solid phase peptide synthesis to afford the prototype for a photoinduced electron transfer-based metal ion chemosensor. The fluorescence of the peptides is modulated upon metal binding. This results from a metal ion-induced conformational change that brings the side chains of the Flu and Dmd amino acids into proximity, thereby favoring photoinduced electron transfer (PET) fluorescence quenching.
- Torrado, Alicia,Imperiali, Barbara
-
p. 8940 - 8948
(2007/10/03)
-
- Iminoxycarboxylates and derivatives as inhibitors of leukotriene biosynthesis
-
The present invention relates to a compound of formula or a pharmaceutically acceptable salt thereof wherein W is optionally substituted aryl or heteroaryl; X is a valence bond, or methylene, divalent alkylene, alkenylene, alkynylene or alkyloxy; Q is a valence bond, or --O--, --S--, >NR4 or >NCOR5 ; Y is optionally substituted phenyl, biphenyl, naphthyl, tetrahydronaphthyl, indolyl, pyridyl, or benzo b!thienyl, thienyl, thiazolyl, or thiazolylphenyl; R1 is alkyl, cycloalkyl, alkoxyalkyl, aryl or arylalkyl, heteroaryl or heteroarylalkyl; R2 is hydrogen, alkyl or hydroxyalkyl; A is a valence bond or is selected from alkylene, alkenylene, alkynylene, cycloalkylene, phenylene, pyridylene, thienylene and furylene; and M is a pharmaceutically acceptable, metabolically cleavable group, --OR6, --NR6 R7, --NH-tetrazoyl, --NH-2-, 3-, or 4-pyridyl, and --NH-2-, 4-, or 5-thiazolyl which inhibit leukotriene biosynthesis and are useful in the treatment of inflammatory disease states. Also disclosed are leukotriene biosynthesis inhibiting compositions and a method for inhibiting lipoxygenase activity and leukotriene biosynthesis.
- -
-
-
- General synthesis of retinoids and arotinoids via palladium-catalyzed cross-coupling of boronic acids with electrophiles
-
A novel approach to the synthesis of retinoids and arotinoids (including heterocyclic analogs) is described which is based on the thallium-accelerated palladium-catalyzed cross-coupling of boronic acids with a variety of electrophiles (the Suzuki reaction).
- Torrado,Lopez,Alvarez,De Lera
-
p. 285 - 293
(2007/10/02)
-
- Demethylation of methoxypyridines with sodium trimethylsilanethiolate
-
Demethylation of methoxypyridines was accomplished in 55-87percent yield by use of ca. 1.5-2.5 equivalents of NaSSiMe3 in 1,3-dimethyl-2-imidazolidinone at 120-180 deg C.This method was found applicable to a methoxyquinoline and methoxypyridines containing a second substituent, such as Cl, OMe, and COOMe.
- Shiao, Min-Jen,Ku, Wei-Shen,Hwu, Jih Ru
-
p. 323 - 328
(2007/10/02)
-
- Synthesis of 2(1H)-pyridones from 2H-pyran-2-ones
-
5-Substituted and 4,5-disubstituted 2(1H)-pyridones (13 examples) with formyl, acyl, alkoxycarbonyl, and trifluoromethyl groups in the 5 position were prepared in 16-97% yield by amination of the corresponding 2H-pyran-2-ones with hexamethyldisilazane or alkyl(trimethylsilyl)amines.
- Kvita
-
p. 883 - 884
(2007/10/02)
-
- Pyridone esters as inotropic agents
-
Described are compounds of the formula STR1 wherein R is hydrogen, lower alkyl, halo, cyano, hydroxy, amino, lower alkylamino, --CH2 NH2, --CH2 OH or --COOR"; R' is hydrogen, lower cycloalkyl or lower alkyl; R' is lower alkenyl, lower alkynyl, lower cycloalkyl, --(W)n Y wherein W is straight or branched chain lower alkyl or lower alkenyl, n is 0 to 5, and Y is Ar, lower cycloalkyl, lower alkenyl, lower alkynyl, --COOZ wherein Z is lower alkyl, STR2 or NAB wherein A and B are, independently, lower alkyl, benzyl or substituted benzyl, and Ar is 2, 3 or 4-pyridyl, pyridazinyl, pyrimidinyl, quinolyl, isoquinolyl, phthalazinyl, quinazolinyl, thiazolyl, phenyl, benzyl, furyl, tetrahydrofuryl or thienyl, unsubstituted or substituted with lower alkyl, lower alkoxy, halo, amino, or --CF3 ; R"' is --COOR", STR3 and X is oxygen or nitrogen; or a pharmaceutically acceptable salt thereof, and their use in the treatment of impaired ventricular myocardial contractility. The compounds exhibit cardiotonic activity.
- -
-
-
- Pyridone esters as inotropic agents
-
Described are compounds of the formula STR1 wherein R is hydrogen, lower alkyl, halo, cyano, hydroxy, amino, lower alkylamino, --CH2 NH2, CH2 OH or COOR"; R' is hydrogen, lower cycloalkyl or lower alkyl; R" is lower alkyl or --CH2 Ar wherein Ar is phenyl, substituted phenyl, furan or thiophene; R'" is COOR", STR2 and x is oxygen or nitrogen; or a pharmaceutically acceptable salt thereof and their use in the treatment of impaired ventricular myocardial contractility. The compounds exhibit cardiotonic activity.
- -
-
-