Darstellung von 2-Methoxycarbomethyliden-1 H-perhido[ 2,l -b] 3-thiazolidinonIm Rahmen der Untersuchungen uber Struktur-Wirkungs-Beziehungen der Hypocholesteramika mit dem 1,4-Dicarboxyl-Grundgeriist haben wir vor kurzem eine Anzahl von Stickstoff enthaltenen Derivaten der 1,4-Dicarbonsauren d a r g e~t e l l t '~) . Es wurde gefunden, dal3 einige davon, besonders die N-substituierten Maleinamidsiiuren, im Tierversuch den normalen bzw. den durch Propylthiouracil erhohten Cholesterinspiegel im Blut senken5). Diese Wirkung ist mit der des Trijodthyronins vergleichbar.

The cyclocondensation of 3‐amino‐2‐iminonaphtho[1,2‐d]thiazole (1) with a series of α‐keto mono‐ and dicarboxylic acid derivatives 5a‐i under different conditions was investigated. When the experiments were performed by refluxing in glacial acetic acid, the corresponding cyclized products, 2‐substituted 3‐oxo‐3H‐naphtho[1′,2′:4,5]thiazolo[3,2‐b][1,2,4]triazines 4 were obtained in fair to good yields. On the other hand, when the reaction was conducted in boiling ethanol, it gave only the open chain condensates 6, or in rare cases, together with minor amount of 4. Since the intermediates 6 exist as mixture of both E‐ and Z‐isomers, cyclization through heating was found insufficient. In any event representative compounds 4b,g,i have been evaluated for anti‐HIV activity, but none of them were active.

Refluxing 3‐amino‐2‐iminonaphtho[1,2‐d]thiazole (1) with diethyl oxalate (2a) in a 2:1 molar ratio in dry pyridine provided 2,2′‐binaphtho[1′,2′:4,5]thiazolo[3,2‐b][1,2,4]triazole (3). On the other hand, when 1 was treated with excess amount of 2a in dimethylformamide, it afforded ethyl naphtho[1′,2′:4,5]thiazolo[3,2‐b][1,2,4]triazole‐2‐carboxylate (4a) on heating and ethyl N‐(2‐iminonaphtho[1,2‐d]thiazol‐3‐yl)oxamate (5) by stirring at room temperature. Cyclization of 5 upon fusion led to the formation of 3‐hydroxy‐2H‐naphtho‐[1′,2′:4,5]thiazolo[3,2‐b][1,2,4]triazin‐2‐one (6). Compound 6 could also be prepared directly from 1 by refluxing either with 2a neatly, in glacial acetic acid or with oxalic acid (2b) in the same medium. The acid form of 4a might be obtained from 1 and 2b on heating in dimethylformamide, but it was decarboxylated to naphtho‐[1′,2′:4,5]thiazolo[3,2‐b][1,2,4]triazole (4b) during the reaction.

Darstellung von 3-substituierten 4 (HI-0x0naphtho[ 1 ',2 ' :4,5] thiazolo[ 3,2-a]pyrimidinen Syntbesis of 3-Substituted 4H-Nepbtho[1',2':4,5]t~olo-[3,2-o]pyWdi11-4-ones

In den vorangegangenen Mitt .I.*) haben wir die Darstellung und Bioaktivitaten einiger 2-0x0und 4-0x0-Derivate der Naphtho-thiazolopynmidin-Reihe beschrieben. Der auffallende Unterschied der Bioaktivitat zwischen den zwei Verbindungsgruppen veranlaate uns zur Darstellung und zur biologischen Priifung der 2,4-Dioxo-Derivate dieses Ringsysterns.036.%6233/85/1212-114 S U2.50/0 (0 VCH Verlagsgesellsehah mbH. D-6940 Weinheim, 1985