Metal complexes of [1,2,4]triazolo-[1,5-a]pyrimidine derivatives

Many first-line treatments for neglected tropical diseases identified by the World Health Organization (WHO) are limited by one or more of the following: the development of drug resistance, toxicity, and side effects, lack of selectivity, narrow therapeutic indices, route of administration, and bioavailability. As such, there is an urgent need to develop viable alternatives to overcome these limitations. The following review provides an overview of all existing metal complexes studied and evaluates the status of these complexes on the respective disease of choice.

Metal Compounds against Neglected Tropical Diseases

Synthesis, antitumor activity and structure-activity relationships of a series of Ru(II) complexes.

Palladium and platinum complexes with HmtpO (where HmtpO = 4,7-dihydro-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine, an analogue of the natural ocurring nucleobase hypoxanthine) of the types [M(dmba)(PPh3)(HmtpO)]ClO4 [dmba = N,C-chelating 2-(dimethylaminomethyl)phenyl; M = Pd or Pt], [Pd(N−N)(C6F5)(HmtpO)]ClO4 [N-N = 2,2′-bipyridine (bpy), 4,4′-dimethyl-2,2′-bipyridine (Me2bpy), or N,N,N′,N′-tetramethylethylenediamine (tmeda)] and cis-[M(C6F5)2(HmtpO)2] (M = Pd or Pt) (head-to-head atropisomer in the solid state) have been obtained. Pd(II) and Pt(II) complexes with the anion of HmtpO of the types [Pd(tmeda)(C6F5)(mtpO)], [Pd(dmba)(µ-mtpO)]2, and [NBu4]2[M(C6F5)2(µ-mtpO)]2 (M = Pd or Pt) have been prepared starting from the corresponding hydroxometal complexes. Complexes containing simultaneously both the neutral HmtpO ligand and the anionic mtpO of the type [NBu4][M(C6F5)2(HmtpO)(mtpO)] (M = Pd or Pt) have been also obtained. In these mtpO−HmtpO metal complexes, for the first time, prototropic exchange...

Palladium(II) and platinum(II) organometallic complexes with 4,7-dihydro-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine. Antitumor activity of the platinum compounds.

Synthesis and antitumor activity of substituted triazolo[4,3-a]pyrimidin-6-sulfonamide with an incorporated thiazolidinone moiety

The formation and isolation of the antitumor drug cisplatin analogue cis-[PtCl2(Hmtpo-N3)2]·2H2O (1) (where Hmtpo = 4,7-H-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine) by reaction of Hmtpo with K2[PtCl4] in HCl (0.5 N) is reported. This complex crystallizes in the monoclinic space group P21/c with unit cell dimensions a = 15.215(2) A, b = 9.629(1) A, c = 13.115(3) A, β = 97.40(2)°, and Z = 4. The molecular structure shows that Pt is in an almost square planar environment, PtN2Cl2, which has a cis configuration. The Hmtpo ligands show a head to head orientation in the solid state and nonrestricted rotation about the Pt−N bonds in solution. The reactivity of the complex to model nucleobases 9-ethylguanine (9-EtGH) and 1-methylcytosine (1-MeC) has been investigated by 1H NMR spectroscopy at 45 °C in aqueous media. The results show that 1 reacts slowly with 9-EtGH (t1/2 ≈ 5 days) by displacement of Cl-, producing cis-[Pt(mtpo-N3)2(9-EtGH-N7)2], which is similar to the major cross-link adduct of cisplatin wi...

cis-[PtCl2(4,7-H-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine)2]: A Sterically Restrictive New Cisplatin Analogue. Reaction Kinetics with Model Nucleobases, DNA Interaction Studies, Antitumor Activity, and Structure−Activity Relationships

J. M. Salas

Papers

cis-[PtCl2(4,7-H-5-methyl-7-oxo[1,2,4]triazolo[1,5-a]pyrimidine)2]: A Sterically Restrictive New Cisplatin Analogue. Reaction Kinetics with Model Nucleobases, DNA Interaction Studies, Antitumor Activity, and Structure−Activity Relationships