Anellierte 2‐Tetrazolyl‐4‐pyrone

Abstract

Es wird uber die Synthese von 2-(1H-Tetrazol-5-yl)-4-oxo-4H-[l]benzofuro[3,2-b]pyran, -4-oxo-4H[ l]benzothieno[3,2-b]pyran und -4,5-dihydro-5-alkyl-4-oxo-pyrano[3,Z-b]indoIen berich-tet . Fused 2-Tetrazolyl-4-pyrones The synthesis of the 2-( 1H-tetrazol-5-yl)-4-0~0-4H-~l]benzofuro[3,2-b]pyrane, -4-oxo-4H-[ 11 benzothieno[3,2-b]pyrane and -4,5-dihydro-5-alkyl-4-oxopyrano[3,2-b]indoles is described. 4,5-Dihydro-5-methyl-4-oxo-pyrano[3,2-b]indol-2-carbonsaureza~3~besitzt eine bemerkenswerte antiallergische Wirkung. Im passiven cutanen Anaphylaxie-Test (PCA-Test) an Ratten betragt die Hemmung bei einer Gabe von 5 mg/kg ip 100 %, peroral 96 O/gZb). Im direkten Vergleich zeigt die Standardsubstanz, das Dinatriumsalz der Cromoglycinsaure (IntalB), bei 10 mglkg getestet, ip eine 89proz. Hemmung, peroral ist das Arzneimittel jedoch unwirksam. Doxantrazo14), ein 1H-Tetrazolyl-Derivat , ist dagegen auch oral wirksam (50proz. Hemmung bei 5 mg/kg). Mit dem Ziel, in moglichst niedriger Dosierung wirksame, oral anwendbare Pharmaka gegen allergisches Asthma zu entwickeln, haben wir linear anellierte, [3 ,Zb]-verknupfte 2-( lH-Tetrazol-5-yl)-4-pyrone des Benzo[b]furans, Benzo[b]thiophens und N-Alkyl-indols synthetisiert.Die Synthese und antiallergische Aktivitat der 4-Oxo-pyrano[3,2-b]indol-tetrazole 8c und 8d ist allerdings kiirzlich von der Warner-Lambert Companyzb) beschrieben worden. Die aus den 4-Pyron-2-carbonsaureethylestern lc, d durch Aminolyse zuganglichen -2-carbonsaureamideZb~ 3, wurden mit Tosylchlorid in DMF in Gegenwart von Pyridin zu den Nitrilen 7c und 7d dehydratisiert, die mit Natriumazid/wasserfreiem Aluminiumchlorid in THF zu den Tetrazolen cyclisierten. 8d hemmt selbst bei einer Dosierung von 1 mg/kg ip im PCA-Test zu 100 %, peroral gegeben, betragt die Hemmung bei einer Dosis von 5 mglkg allerdings nur 70 %.

Efficient tandem synthesis of a variety of pyran-annulated heterocycles, 3,4-disubstituted isoxazol-5(4H)-ones, and α,β-unsaturated nitriles catalyzed by potassium hydrogen phthalate in water

“…When ethyl 4-chloroacetoacetate (17) was used instead of ethyl acetoacetate (14) the 3CR proceeded furnishing another type of 3,4-disubstituted isoxazol-5(4H)-one derivative (entries [15][16][17][18][19][20][21][22][23]. The results for this 3CR are presented in Table 7.…”

“…Treatment of aldehydes with ethyl cyanoacetate (3b) also produced a,b-unsaturated nitriles in excellent yields under similar reaction conditions. Compared with malononitrile (3a), reaction of ethyl cyanoacetate (3b) with the same aromatic aldehydes required longer reaction times (entries [13][14][15][16][17][18][19][20][21][22][23].…”

“…Over the past few years, both these six-membered oxygen-containing heterocycles and their derivatives have attracted much attention, owing to their wide range of biological activity, for example spasmolytic, diuretic, anticoagulant, antianaphylactic [13], antimicrobial [14], antifungal [15], antibacterial [16], antioxidant [17], antileishmanial [18], antitumor [19], local anesthetic [20], antihistaminic [21], and antiallergenic [22] activity and because of their use for treatment of Alzheimer's disease [23] and schizophrenia [24]. Moreover, several chromenes are widely used as pigments [25], cosmetics [26], and laser dyes [27].…”

Transformation of substituted 3-hydroxy-4-[(2E)-3-arylprop-2-enoyl]-1,5-dihydro-2H-pyrrol-2-ones by the action of I2/DMSO into derivatives 2-aryl-5,6-dihydropyrano[2,3-c]pyrrole-4,7-diones

“…This is, mainly, because themain research focus has been paid on the synthesis of 2,(3)-substituted and 2,3-disubstituted chromones [6][7][8], whereas synthetic methodologies for obtaining of pyronecondensed rings investigated and developed insufficiently. Existing reviews summarize synthetic approaches to pyrano-pyrazole-fused compounds [9], azachomones and azachromanones [10]. Some methods for the synthesis of tricyclic heterocyclic systems that include a pyron ring have also been developed [10,11].…”

“…Existing reviews summarize synthetic approaches to pyrano-pyrazole-fused compounds [9], azachomones and azachromanones [10]. Some methods for the synthesis of tricyclic heterocyclic systems that include a pyron ring have also been developed [10,11].…”