Antitumour

Review Problem 3 Tliis odd-looking molecule (TM 34) was used by Corey as an intermediate in the synthesis of maytansine, an antitumour compound. 

Most drugs in the pyrimidine series fall into four categories the barbiturates, the sulfonamides, the antimicrobials and the antitumour agents. In addition there are innumerable pyrimidines with diverse biological activities, some of which are in use. 

The 1- and 3-deaza analogues (463a, 463b) of the DHFR-inhibitory antitumour drug methotrexate have also been investigated (71JOC2818). 

Pyrimidine, 4-fluoro-2-isopropyl-synthesis, 3, 140 Pyrimidine, 4-fluoro-2-methoxy-synthesis, 3, 140 Pyrimidine, 4-fluoro-2-methyl-NMR, 3, 63 Pyrimidine, halo-aleoholysis, 3, 100 aminolysis, 3, 99 as antitumour agents, 3, 152 bipyrimidines from, 3, 103 Buseh biaryl synthesis, 3, 103 hydrolysis, 3, 101... 

The AMAPs (2-[ arylmethyl amino]-l,3-propanediols) are a class of planar polycyclic aromatic derivatives, which contain polar side-chains. They are known to be DNA intercalators and possess broad spectrum antitumour activity. An approach to C-radiolabelled AMAP derivative 40 used the Bucherer reaction as an initial starting reaction. 2-Naphthol was reacted with 4-bromophenylhydrazine 38 in the presence of sodium metabisulfite and HCl to afford 39. Subsequent derivatisation of 39 afforded 40. 

The mechanism of action of antitumour platinum coordination compounds. J. J. Roberts, Adv. Inorg. Biochem., 1981, 3, 273-332 (141). 

Platinum complexes probes of polynucleotide structure and antitumour drugs. S. J. Lippard, Acc. Chem. Res., 1978,11, 211-217 (56). 

A similar synthetic strategy was applied in the synthesis of menogaril 83, another important anthracycline antitumour antibiotic, and to the synthesis of the tricyclic core of olivin 87, the aglycon of the antitumour antibiotic olivomycin [61,62]. In both cases a tandem benzannulation/Friedel-Crafts cyclisation sequence yielded the tetracyclic and tricyclic carbon core, respectively (Scheme 42). 

Intensive studies towards the total synthesis of fredericamycin A 91 culminated in the enantioselective synthesis of this potent antitumour antibiotic [63]. 

The synthesis of the naphthalene rings found in the gilvocarcin group and in the rubromycin class of natural products via benzannulation was also reported. Both classes show promising antitumour activity [67,68]. 

One of the pectic fractions from Angelica acutiloba showed potent antitumour activity, and this polymer was rich in the AG-I type structure, indicating that the 4-linked galactose units are important for this activity [40]. 

Antitumour activity has been reported for alkyltins, particularly dibutyltin. The effect in mouse skin initiation/promotion protocols showed dibutyltin inhibiting the promotion stage (Arakawa Wada,... 

The antitumour drug temozolomide 24 (R = Me) has been attracting attention and two new routes have been develqjed. One starts from 5-aminoimidazole-4-caiboxamide, whilst the other starts from 5-diazoimidazole-4-carboxamide which reacts with trimethylsilyl isocyanate to give 8-carbamoylimidazo[5,l-[Pg.272]

The pyrrolopyrimidines 100 react with chloroamines to yield cyclic products 101 which are being investigated for antitumour activity <95MI08 96CA(124)117234>. 

Heald RA, Stevens MF (2003) Antitumour polycyclic acridines. Palladium(O) mediated syntheses of quino [4,3,2-kl] acridines bearing peripheral substituents as potential telomere maintenance inhibitors. Org Biomol Chem l(19) 3377-3389... 

The most important aspect of coralyne is its ability to inhibit DNA relaxation in a fashion significantly similar to the most potent antitumour alkaloid camptothecin, which is known to exert this property [242], Presumably, the most notable biological action of these alkaloids appears to be topoisomerase inhibition [238-242], which has direct relevance to their DNA intercalating property. In this context. Pilch et al. [167] described a mixed binding mode model (Fig. 16) in which the protoberberine structure constitutes portions that can intercalate or bind to the minor groove of DNA. Wang et al. [240] demonstrated that coralyne (Ci) and several of its derivatives (Ce to Ch) (Scheme 5), including the partial saturated... 

Hibbs, J.B. (1991). Synthesis of nitric oxide from L-atginine a recently discovered pathway induced by cytokines with antitumour and anti-microbial activity. Res. Immunol. 142, 565-569. 

Schein, P.S., Cooney, D.A. and Veron, M.L. (1967). The use of nicotinamide to modify the toxicity of streptozotocin diabetes without loss of antitumour activity Cancer Res. 27, 2324-2332. 

Anticancer agents — see Antibiotics, Antitumour agents Anticonvulsant drugs, 3 (1963) 261 ... 

Platinum antitumour agents, 24 (1987) 129 Platelet aggregration, inhibitors of,... 

Sava, G., Bergamo, A. Dyson, P. J. Metal-based antitumour drugs in the post-genomic era what comes next Dalton Trans. 40, 9069-9075 (2011). 

The starting point of this article is the discovery by Rosenberg and his collaborators of the activity of certain platinum compounds as antitumour agents (7). Here we wish to introduce the chemistry of these agents, which will be relatively familiar to inorganic chemists, but not to chemists and biochemists of other disciplines. At the same time we wish the inorganic chemist to see the relevance of the chemistry to biological fields. 

In total the analysis of protein complexes indicates that methionine is the most likely group to bind to [PtCU]2 and [PtenClfc] probably by a displacement reaction. However a specific attachment to another residue such as histidine or sulphydryl can not be ruled out. Furthermore the antitumour activity is that of cis- [Pt (NH 3) 2CI2] and the di-functional character of this reagent has not been revealed so far by the above studies. In fact no attempt has been made to uncover the difference between [PtCl2(NH3)2] in its cis and fraMS-forms. 

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