Studies on positive inotropic agents. II. Synthesis of (4-substituted 1-piperazinylcarbonyl)-2-(1H)-quinolinone derivatives.

Tominaga, Michiaki; Yo, Eiyu; Ogawa, Hidenori; Yamashita, Shuji; Yabuuchi, Youichi; Nakagawa, Kazuyuki

doi:10.1248/cpb.34.682

Cited by 11 publications

(6 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…: 309–311 °C); 1 H NMR (500 MHz, [D 6 ]DMSO): δ =2.40 (t, 3 J= 7.7 Hz, 2 H; C 3 H 2 ), 3.20 (t, 3 J= 7.7 Hz, 2 H; C 4 H 2 ), 7.03 (d, 3 J= 8.0 Hz, 1 H; CH ar ), 7.21 (dd, 3 J= 8.0 Hz, 3 J= 7.2 Hz, 1 H; C 7 H), 7.41 (d, 3 J= 7.2 Hz, 1 H; CH ar ), 10.13 (s, 1 H; NH), 12.54 ppm (s, 1 H; OH); 13 C NMR (90.6 MHz, [D 6 ]DMSO): δ =22.6 (CH 2 ), 29.9 (CH 2 ), 118.6 (CH ar ), 123.7 (CH ar ), 124.8 (C q,ar ), 126.9 (CH ar ), 130.5 (C q,ar ), 139.5 (C q,ar ), 168.5 (CO), 170.2 ppm (CO); IR (KBr): $\tilde \nu $ =3420 (m, OH), 3200 (m, NH), 3070 (m, CH ar ), 2924 (s, CH al ), 1720 (vs, CO), 1682 (vs, NHCO), 1469 (s, CH al ), 1388 (vs), 1290 (s, CN), 755 cm −1 (w, CH ar ); MS (70 eV, EI): m / z (%): 191 (100) [ M + ], 163 (42) [ M + −CO], 146 (8) [ M + −COOH], 118 (10). The spectroscopic data were in accordance with reported data 21…”

Section: Methodssupporting

confidence: 87%

“…Preparation of the substrate : Commercially available ethyl 3,3‐diethoxypropionate ( 3 ) was converted into 3‐ethoxyacryloyl chloride ( 4 ) by a known two‐step procedure (Scheme ) 20. Acylation of m ‐aminobenzoic acid with chloride 4 led to an anilide (75 % yield) which was cyclized under acidic conditions to an unsaturated quinolone (89 % yield) 21. The previously reported hydrogenation of the quinolone21 to dihydroquinolone 5 was conducted at 60 °C under 2 MPa (20 bar) H 2 pressure with Pd/C as the catalyst (10 mol %).…”

Section: Resultsmentioning

confidence: 99%

“…Acylation of m ‐aminobenzoic acid with chloride 4 led to an anilide (75 % yield) which was cyclized under acidic conditions to an unsaturated quinolone (89 % yield) 21. The previously reported hydrogenation of the quinolone21 to dihydroquinolone 5 was conducted at 60 °C under 2 MPa (20 bar) H 2 pressure with Pd/C as the catalyst (10 mol %). Under these conditions the hydrogenation proceeded in 75 % yield.…”

Section: Resultsmentioning

confidence: 99%

“…M.p. 307 °C (lit 21$\tilde \nu $ =3420 (m, OH), 3200 (m, NH), 3070 (m, CH ar ), 2924 (s, CH al ), 1720 (vs, CO), 1682 (vs, NHCO), 1469 (s, CH al ), 1388 (vs), 1290 (s, CN), 755 cm −1 (w, CH ar ); MS (70 eV, EI): m / z (%): 191 (100) [ M + ], 163 (42) [ M + −CO], 146 (8) [ M + −COOH], 118 (10).…”

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Enantioselective [4+2]‐Cycloaddition Reaction of a Photochemically Generated o‐Quinodimethane: Mechanistic Details, Association Studies, and Pressure Effects

Grosch

Orlebar

Herdtweck

et al. 2004

Chemistry A European J

View full text Add to dashboard Cite

1,2,3,4-Tetrahydro-2-oxoquinoline-5-aldehyde (2) was prepared from m-aminobenzoic acid and 3-ethoxyacryloyl chloride (4) in 19 % overall yield. Compound 2 underwent a photochemically induced [4+2]-cycloaddition reaction with various dienophiles upon irradiation in toluene solution. The exo product 10 a was obtained with acrylonitrile (9 a) as the dienophile, whereas methyl acrylate (9 b) and dimethyl fumarate (9 c) furnished the endo products 11 b and 11 c (69-77 % yield). The reactions proceeded at -60 degrees C in the presence of the chiral complexing agent 1 (1.2 equiv) with excellent enantioselectivity (91-94 % ee). The enantiomeric excess increases in the course of the photocycloaddition as a result of the lower product association to 1. The intermediate (E)-dienol 8 was spectroscopically detected at -196 degrees C in an EPA (diethyl ether/isopentane/ethanol) glass matrix. The association of the substrate 2 to the complexing agent 1 was studied by circular dichroism (CD) titration. The measured association constant (K(A)) was 589 M(-1) at room temperature (25 degrees C) and normal pressure (0.1 MPa). An increase in pressure led to an increased association. At 400 MPa the measured value of K(A) was 703 M(-1). Despite the stronger association the enantioselectivity of the reaction decreased with increasing pressure. At 25 degrees C the enantiomeric excess for the enantioselective reaction 2 + 9 a-->10 a decreased from 68 % ee at 0.1 MPa to 58 % ee at 350 MPa. This surprising behavior is explained by different activation volumes for the diastereomeric transition states leading to 10 a and ent-10 a.

show abstract

Section: Methodssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Enantioselective [4+2]‐Cycloaddition Reaction of a Photochemically Generated o‐Quinodimethane: Mechanistic Details, Association Studies, and Pressure Effects

Grosch

Orlebar

Herdtweck

et al. 2004

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…Unsubstituted simple 2(1H)-quinolinonecarboxylic acid was prepared according to a previous report. 10 The Palladium-catalyzed hydrogenation of 2(1H)-quinolinones 36 or 42 in acetic acid gave the 3,4-dihydro derivatives 43 and 44, respectively. Introduction of a carboxyl function into the 6-position of alkyl-substituted quinolinones was achieved by Friedel-Crafts reaction with chloroacetyl chloride followed by King's reaction 13 (Scheme 3).…”

Section: Chemistrymentioning

confidence: 99%

Novel Selective Hindlimb Vasodilators: Synthesis and Biological Activity of 1-Acyl-4-aminopiperidine Derivatives

et al. 2003

Self Cite

View full text Add to dashboard Cite

A series of 6-(4-amino-1-piperidinyl)carbonyl-2(1H)-quinolinones, and their open form derivatives, were synthesized and evaluated for their ability to stimulate femoral artery blood flow (FBF) in the canine hindlimb. All members of this series stimulated FBF, and subsequent experiments revealed that selected members of this series produced minimal changes in coronary blood flow or systemic blood pressure. Compound 25 was the most promising agent in this respect, and clinical trials are now ongoing to evaluate the effectiveness of this drug as a novel treatment for intermittent claudication and Raynaud's phenomenon.

show abstract

Hochenantioselektive Diels‐Alder‐Reaktion eines photochemisch erzeugten o‐Chinodimethans mit Olefinen

et al. 2003

View full text Add to dashboard Cite

Professor Manfred T. Reetz zum 60. Geburtstag gewidmet Eine photochemische Alternative zur klassischen DielsAlder-Reaktion eines Diens mit einem Dienophil besteht in der Erzeugung eines hochreaktiven o-Chinodimethans durch intramolekulare H-Abstraktion eines o-Alkyl-substituierten Benzaldehyds A (Schema 1) und dessen Umsetzung mit Alkenen bei tiefer Temperatur.[1] Diese Reaktion wurde zum ersten Mal 1961 von Yang und Rivas beobachtet [2] und in der Folge intensiv untersucht. Von den beiden gebildeten Enolen (Z)-B und (E)-B geht nur das (E)-Diastereomer (t > 1 s) die Reaktion ein, während das (Z)-Diastereomer schnell (t = 30 ns-1 ms) tautomerisiert. [3, 4] Als Konsequenz dieser Selektivität und aufgrund der durch die Wahl des Alkens vorgegebenen exo-oder endo-Selektivität erfolgt die Produktbildung mit hoher Diastereoselektivität, wobei bis zu vier stereogene Zentren gleichzeitig aufgebaut werden. Wichtige Anwendungen dieser Reaktion für den Aufbau hochsubstituierter biologisch relevanter Tetraline wurden beschrieben. [1,5] Trotz ihres präparativen Potenzials existiert unseres Wissens kein Beispiel einer enantioselektiven Diels-Alder-Reaktion von o-Chinodimethanen. Wir sahen eine Möglichkeit der enantioselektiven Reaktionsführung in der Verwendung des Substrats 1 (Schema 2), das mit dem Lactamring eine nichtkovalente Bindungsstelle zur Wasserstoffbrückenbindung [6] aufweist. Das Substrat wurde in einer einfachen Reaktionssequenz ausgehend von m-Aminobenzoesäure hergestellt. [7] In Gegenwart eines chiralen Komplexierungreagens des Typs 3[8] sollten sich die enantiotopen Seiten des photochemisch erzeugten o-Chinodimethans differenzieren lassen. Bei geeigneter Wahl des Dienophils 2 sollten auf diesem Weg Absolut-und Relativkonfiguration der Produkte kontrolliert werden können. Die Regioselektivität ist bei acceptorsubstituierten Olefinen (2, A = Acceptor) eindeutig. In der Tat ergaben erste Versuche mit dem Substrat 3 und den Alkenen 2 eine extrem hohe Seitendifferenzierung (Tabelle 1) bei perfekter Regioselektiviät und guter bis exzellenter einfacher Diastereoselektivität. [9] Acrylnitril (2 a) lieferte bevorzugt das exo-Diastereomer exo-4 a (Tabelle 1, Nr. 1-5), während Acrylsäuremethylester (2 b) und Fumarsäuredimethylester (2 c) eine klare endoSelektivität zugunsten von endo-4 b (Nr. 6-8) und endo-4 c (Nr. 10, 11) aufwiesen. Die Reaktion verläuft außerordentlich schnell: Bei Raumtemperatur sind bereits nach 5 bis 10 Minuten 95 % des Substrats 1 umgesetzt, bei À60 8C ist der gleiche Umsatz nach 30 Minuten erreicht. Die Enantioselektivitäten sind hervorragend und übertreffen alle Ergebnisse, die wir bisher bei Photocycloadditionen [10] und Photocyclisierungen [11] erhalten haben. Selbst bei Verwendung von 1.2 ¾quivalenten des chiralen Komplexierungreagens 3 wurden bei À60 8C Enantioselektivitäten von über 90 % ee

show abstract

Studies on positive inotropic agents. II. Synthesis of (4-substituted 1-piperazinylcarbonyl)-2-(1H)-quinolinone derivatives.

Cited by 11 publications

References 0 publications

Enantioselective [4+2]‐Cycloaddition Reaction of a Photochemically Generated o‐Quinodimethane: Mechanistic Details, Association Studies, and Pressure Effects

Enantioselective [4+2]‐Cycloaddition Reaction of a Photochemically Generated o‐Quinodimethane: Mechanistic Details, Association Studies, and Pressure Effects

Novel Selective Hindlimb Vasodilators: Synthesis and Biological Activity of 1-Acyl-4-aminopiperidine Derivatives

Hochenantioselektive Diels‐Alder‐Reaktion eines photochemisch erzeugten o‐Chinodimethans mit Olefinen

Contact Info

Product

Resources

About