Quinoline compounds biologically active

The Doebner-von Miller reaction was used as a method of choice for the synthesis of several biological active quinoline compounds. The anti-malarial drug primaquine, which acts against the hepatic stage of plasmodia infection, was synthesized by a Skraup reaction fi om 4-methoxy-2-nitroaniline and glyceron in the presence of sulfiiric acid. The nitro group was then reduced and alkylated with 4-bromo-l-phthalimidopentane to provide the protected primaquine, which was deprotected by using hydrazine. ... 

Numerous structural modification studies of ellipticine have been conducted. It is found that side-chain substitution has considerable influence on the biological activity to compounds of this type. A pyridopyrrolo[2,3-g]iso-quinoline derivative, BD-40 (48) [235, 236], has demonstrated potent activity against many different experimental tumours including leukaemia L1210 and the Friend virus leukaemia. It is also active against the Moloney strain of murine sarcoma virus [237]. Phase I clinical study of (48) has been conducted [238, 239]. 

Finally, the quinoline ring can be methylated at the 3 position with retention of biologic activity. The starting quinoline is prepared by the same scheme as that used for the desmethyl compound by substituting the methylated oxosuccinate ester, S6, in the sequence. The initial quinoline carboxylate (87) is taken on to the dichloro compound (88) by the standard reactions. Condensation with the ubiquitous diamine (76) affords sontoquine (89)... 

A variety of substituted dibenzo-fused derivatives 126 have been prepared for evaluation of their biological activities. The synthesis of these compounds involves the reaction of o-acylanilines with pyrroloindolones 125, in boiling butan-l-ol with pyridinium />-toluenesulfonate as catalyst (Equation 8). Compounds such as 126 which contain the benzo[5,6]pyrrolizino[l,2-A]quinoline skeleton exhibit cytotoxicity against several cancer cell lines <2004BML2363>. 

The reduction of 2, either catalytically or with zinc in acetic acid, leads to 3-amino-4-hydroxy-2-quinolone 20 [72TH000], These amino compounds are rather unstable they dimerize with loss of ammonia to "bis-amines", which in turn are readily oxidized to dyes similar to those obtained from ninhydrin and primary amines [68M1205] [68M1543], The amino derivatives 20 are therefore conveniently converted into 0,N-diacetyl derivatives, the N-acetyl derivative 21, or its dehydrated form, the oxazolo derivative 22 [95MI000], The variety of biological activity of oxazolo-quinolines of type 22 has been detected only in recent years [94JHC1647],... 

Pyridines and their benzo-derivatives have played an important role in the synthesis of biologically active synthetic and natural substances. As a result, the construction of this molecular architecture has attracted the attention of a diverse array of synthetic methodologies. Notably, transition metal catalysis, radical reactions and cycloaddition chemistry-based methods have been developed for the construction of this important ring system. Detailed herein is a summary of the methods developed for the synthesis of pyridines, quinolines, isoquinolines and piperidines that were disclosed in the literature in 2002. Rather than survey all existing methods for the construction of these compound classes, this review will serve as a supplement and update to the review published last year in this series. 

Quinolines are widely used heterocyclic compounds in organic chemistry (Rees and Smithen, 1964 Popp, 1968), while 3-nitrochromenes are another important class of heterocyclic compounds due to their biological activity (Bianco et al., 1977) and their importance as precursors of flavonoids (Rao et al., 1984), amines (Booth et al., 1973), and other important targets (Adrieu et al., 1976 Aramaki et al., 1993). 

Many aromatic systems have been oxidized by Fremy s salt, including phenols, naphthols, anilines, quinolines, indoles, carbazoles, and polyaromatic systems. The review articles by Zimmer and Parker can be consulted for specific examples. Slight modifications of the mechanism presented in Scheme 20 explain the oxidation of most of these classes of compounds [63], Oxidations by Fremy s salt and related nitroxides have been used in the total synthesis of several biologically active compounds [64], Recent examples can be found in the syntheses of the antitumor antibiotic streptonigrone (34), the antitumor agent EO-9 (35), the anti-rheumatic agent epoxyquinomicin B (36), and the antineoplastic agent makaluvamine C (37) (Scheme 21) [65]. 

Carboxylic acid substituted quinolin-4-one derivatives constitute another class of biologically active compounds often known under the collective name quinolones . The development of quinolone antibacterials since the discovery of naphthyridine agent, nalidixic acid, has progressed with periods of great innovation. 

Pyranoquinoline alkaloids are another important group of quinoline derivatives that possess strong biological activities, from potent inhibitors of platelet aggregation such as zanthodioline, to cytotoxic compounds acting selectively to breast cancer cells such as huajiaosimuline."... 

Benzo-annelated nitrogen heterocycles (indoles, quinolines, isoquinolines, etc.) are often found to be a part of biologically active compounds of both natural and synthetic origin. In a considerable body of data on the syntheses of these compounds, which have so far been documented in the literature, the crucial step is vicarious nucleophilic substitution of hydrogen in nitroarenes. Good examples are presented by the synthesis of nordehydrobufotenine [49], eupolauramine [50, 51], damirone [52], and aklavinone [53]. 

---