Reaction of 4-alkylamino-2-chloroquinoline-3-carbonitriles 4a-e with an equimolecular amount of ethyl mercaptoacetate gave, in each case, the corresponding ethyl 4-alkylamino-3-aminothieno[2,3-b]quinoline-2-carboxylates 7a-e. Diazotization of 7a-e afforded the novel tetracyclic ring system ethyl 1-alkyl-1H-5-thia-1,2,3,6-tetraazaacephenanthrylene-4-carboxylates 8a-e. Refluxing 7a-e with an excess of triethyl orthoformate yields the new ethyl 1-alkyl-1H-5-thia-1,3,6-triazaacephenanthrylene-4-carboxylates 9a-e. Reacting 9b, c, as example, with an excess of cyclohexylamine (2a) in boiling DMF furnished the corresponding amides 10a, b in good yields.We have reported in previous parts 1-3 of this series on the synthesis of novel tetracyclic ring systems, containing the quinoline skeleton, with potential pharmaceutical activity, such as pyrazolotriazinoquinolines 1,2 and pyrrolopyrimidoquinolines. 3 Fused heterocycloquinolines are a large group of polyheterocycles with diverse, interesting biological activities. They are reported to possess significant antiinflammatory, 4,5 antitumor, 6,7 antibacterial 8,9 and potent Bradykinin (BK) B 1 and B 2 receptor antagonist properties. 10 Moreover, some of the sulfur-containing fused quinolines and particularly thienoquinolines have recently drawn much attention due to their considerable biological and pharmacological activities as antitumor, 11 antibacterial, 11,12 drug resistance modulators, 13 memory enhancers, 14 antiinflammatorics, immunoregulators, analgesics and antipyretics. 15 Others are reported to exhibit good antiallergics 16 and antianaphylactic activities. 17Because of these findings, our interest was focused on investigating efficient and convenient routes to construct the novel title ring systems. To the best of our knowledge, however, there are only few literature reports about the synthesis of linear, anellated pyrimidothienoquinolines 18-20 and 1,2,3-triazinothienoquinolines. 16,20 Moreover, a survey on the synthesis of perianellated tetracyclic pyrimidothienoquinoline and 1,2,3-triazinothienoquinoline ring systems revealed that these ring systems have been largely ignored. In connection with our ongoing program of synthesis of pharmacologically interesting new heterocyclic systems containing the quinoline moiety, 1,21-24 we now succeeded in the synthesis of the first representatives of so far not accessible tetracyclic systems, namely ethyl 1-alkyl-1H-5-thia-1,2,3,6-tetraazaacephenanthrylene-4-carboxylates and ethyl 1-alkyl-1H-5-thia-1,3,6-triazaacephenanthrylene-4-carboxylates.In the syntheses presented in this paper, the conveniently available 2,4-dichloroquinoline-3-carbonitrile (1) 1 is employed as starting material. It is known that the chlorine atom in the 4-position of 1 is more labile than that in the 2-position and is more easy to displace using nucleophiles, 25 therefore, 1 was reacted with alkylamines 2 in order to obtain the required key intermediate 4 for subsequent thiophene ring closure. Reaction of 1 with an excess of the appropriate alkylamin...

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2,4-Dichloroquinoline-3-carbonitrile (1) with phenylhydrazine in DMF at room temperature gave the 3-amino-4chloro-1-phenylpyrazolo[4,3-c]quinoline (2). Reaction of 2 with phenyl isothiocyanate afforded the novel fused tetracyclic ring system 1,5-diphenyl-1,5-dihydro-1,2,3,5,6-pentaazaaceanthrylene-4(3H)-thione (7). Refluxing 2 with excess of a primary amines 8a-d in boiling DMF yielded the corresponding aminopyrazolo[4,3-c]quinolines 9a-d which react with an excess of triethyl orthoformate to furnish 5-substituted 1-phenyl-1,2,3,5,6-pentaazaaceanthrylenes 11a-d. Reacting 9a with acetic anhydride does not give the expected tetracyclic compound 12, but instead the acetamide 13 is obtained. With triethyl orthoacetate the corresponding iminoester 14 is formed. When compound 14 was refluxed in DMF containing NaH it cyclised to the 4-methyl analogue 12.Scheme 1 Pyrazolo[4,3-c]quinoline formation from nitrile 1.Scheme 2 Formation of 1,5-dihydro-1,2,3,5,6-pentaazaaceanthrylene derivatives (7, 11a-d).Scheme 3 The 4-methyl compound 12, and derivatives of the amine 9a.

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