Trequinsin

More then a dozen representatives of the above ring systems were introduced into the human therapy. Actisomide (2) and trequinsin (3) are used as antiarrhytmic and antihypertensive agents, respectively. Sunepitron (4), a a 2-adrenoceptor antagonist, is under clinical trials for the treatment of anxiety and depression. Representatives of the third generation of antibacterial quinolone-3-carboxylic acids the blockbluster ofloxacin (5), its levorotatory enantiomer, levofloxacin (6), and rufloxacin (7) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (8) is under development. Praziquantel (9) is widely applied for the treatment of schistosomes- and cestode-caused infection in both veterinary and human therapies (Scheme 4). 

Demethylation of trequinsin (3) with a 65 35 mixture of AcOH and 48% HBr at 115 °C for 3 h gave mainly 10-hydroxyl derivatives 148 (R = r = H), which was accompanied by traces of its 9-hydroxyl and 9,10-dihydroxy derivatives. In boiling 48% HBr for 2 h its 9,10-dihydroxy derivative formed in 63% yield (98IJC(B)1). 9-Methoxy group of 3 and that of its 2-[(2,6-dimethyl-4-carboxyphenyl)imino] derivative 178 (R = COOH) was selectively demethylated by the treatment with 60% NaOH and EtSH in HMPA. Treatment of 3 with pyridine HCl in boiling pyridine for 20 min afforded its 9,10-dihydroxy-3-desmethyl derivative in 65% yield. 4 -Hydroxymethyl... 

It was assumed that pyridine derivative 181 yielded pyrido[l,2-c]pyrimidine betaine 182 under catalytic hydrogenation conditions over (5,S)-Et-DuPHoS-Ph catalyst (99TL1211). 6,7-Dehydro derivative 184 of trequinsin (3) was obtained from pyrimidinone 183 by heating in an 1 1 mixture of MeOH and cone. HCl under reflux (97IJC(B)349). 

Treatment of l,3,4,6,7,llb-hexahydro[l,3]oxazino[3,4- ]quinazolin-l-one with LAH in boiling THF gave 2-(2-hydroxyethyl)-l-methylquinoline <2003T6785>. Pyrimidinone 107 was obtained from trequinsin 106 on the action of NaH, followed by the treatment with Mel (Equation 17) <1997IJB349>. The reaction of7-(benzotriazol-l-yl)-6,7-dihydro-l//,3/7,5//-pyrido[3,2,l-zy][3,l ]bcnzoxazine with PhMgBr led to ring-opened l-benzyl-4-(benzotriazol-l-yl)-8-hydroxymethyl-l, 2,3,4-tetrahydroquinoline < 1995JOC3993>. 

Trequinsin 106, a selective phosphodiesterase-3 (PDE3) inhibitor <2005MI6412>, and actisomide 225 have been introduced into human therapy as antihypertensive and antiarrhythmic agents, respectively. 

MRP5 (ABCC5) Human DNP-SG, CAMP, cGMP, GSH Drugs adefovir, 6-MP Probenecid Drugs benzbromarone, sildenafil, trequinsin, zaprinast... 

Treatment of trequinsin (19) with dimsyl ion gave the ring-opened product 114 when a short reaction period (5 min) was applied, but a longer reaction period led to a mixture of 115 and 114 (reaction period 15 min), or a mixture of 116 and 115 (reaction period 45 min) (90JOC5117). Similar... 

MRP6 (ABCC6) Liver, kidney Basolateral heavy metals (Cd), GSH, 6-mercaptopurine Enothelial receptor antagonist zaprinast, trequinsin, sildenafil... 

Hg(OAc)2-EDTA afforded ring-opened products. Treatment of trequinsin (34), and other 6,7-dihydro derivatives of the 5,6-benzologue of (10) with dimsyl ion gave various ring-opened products <90JOC5117,91CB111>. 

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