Carlos Peinador

A new doubly interlocked [2]catenane.

The synthesis and the crystal structure of a doubly braided [2]catenane, a new molecular Solomon link, obtained by a 5-component-self-assembly process based on coordinative bonds, pi-donor/pi-acceptor interactions, and hydrogen bonding is reported.

Synthesis and antihistaminic activity of 2-guanadino-3-cyanopyridines and pyrido[2,3-d]-pyrimidines

2-Guanadino-3-cyanopyridines 8-33 and pyrido[2,3-d]-pyrimidines 35-52 were synthesized by nucleophilic displacement and cyclization of the chloroamidines 6a-d easily obtained by reaction of 2-aminocyanopyridines 5a-d with phosgene iminium chloride and their action on the release of histamine by mast cells examined under immunological and chemical stimulus, with and without pre-incubation. Several 2-guanadino-3-cyanopyridines and pyrido[2,3-d]-pyrimidines are shown to be inhibitors of the release of histamine when stimulated with ovoalbumin as antigen or with polymer 48/80 as chemical stimulus. Guanadino-3-cyanopyridine 30 and pyrido[2,3-d]-pyrimidine 49 are the more active of all, inhibiting the release of histamine in all the conditions tested (30-60% inhibition). Guanadinocyanopyridines 15, 17, and 19 are very potent stimulators of the release of histamine (150-300%) while pyrido[2,3-d]-pyrimidines are mostly inactive. Compounds 28 and 14 present moderate in vitro cytotoxic activity against P-388, A-549, HT-29, and MEL-28 cell lines.

Piperazine N-substituted naphthyridines, pyridothienopyrimidines and pyridothienotriazines: new antiprotozoals active against Philasterides dicentrarchi

New antiprotozoals active against Philasterides dicentrarchi, the causative agent of scuticociliatosis in farmed turbot and Black Sea bass-bream, have been synthesised and tested. The most active compounds posses a piperazine ring, generally N-bonded to the heterocycle, and are the 1,8-naphthyridines, 2f and 5o, the pyridothienopyrimidine (7), and the pyridothienotriazines, 8, 9, 12d, 12f, 12h, 12m and 12k. Pyridothienotriazine (12k) presents the same activity (Lethal Dose, LD=0.8/1.5 mg L(-1)) as the well-known antiparasitics niclosamide and oxyclozanide.

A novel synthesis of pyrano[2,3-d]pyrimidine derivatives

Abstract A ready one-pot preparation for pyrano[2,3-d]pyrimidines from appropriately substituted pyran derivative and N,N-dimethyldichloromethyleniminium chloride (phosgeniminium chloride) is reported.

Synthesis, antihistaminic and cytotoxic activity of pyridothieno- and pyridodithienotriazines

Abstract The synthesis of pyrido[3′,2′:4,5]thieno[3,2- d ]-1,2,3-triazines 7a-n and 8a-c and pyrido[3′,2′:4,5]dithieno[3,2- d ]-1,2, 3-triazines 15 and 16a-c , and their inhibitory action on the release of histamine from rat mast cells under immunological and chemical stimulus are presented. Compounds 7b and 16a are strong inhibitors under all the conditions tested while 16c is a good inhibitor in all conditions except when it is preincubated with ovoalbumin. Compounds 7k, 7m and 7n are good inhibitors in the immunological experiments but are practically inactive under chemical stimulus. Compounds 6a and 15 show in vitro cytotoxic activity against several human and mouse tumoral cell lines with IC 50 values well under 1 mg/mL.

6-Dimethylamino 1H-pyrazolo[3,4-d]pyrimidine derivatives as new inhibitors of inflammatory mediators in intact cells.

The synthesis of 6-dimethylamino 1H-pyrazolo[3,4-d]pyrimidines substituted at positions 1 and 4, and their effects on murine macrophage and human neutrophil functions are described. Several compounds and especially 4b-6b are potent inhibitors of PGE(2) generation in murine macrophages. This action is related to a direct effect on COX-2 activity without affecting the enzyme expression. Some of these compounds also inhibited COX-1 and COX-2 in human monocytes and 4b showed selectivity for COX-2 inhibition.

Pyrazolopyrimidines : synthesis, effect on histamine release from rat peritoneal mast cells and cytotoxic activity

A series of 1H-pyrazolo[3,4-d]pyrimidines (3--6) substituted at positions 1 (R(1)=Ph, H, tert-butyl and ribosetribenzoate), 4 (R(2)=chlorine, nitrogen and oxygen nucleophiles), and 6 (dimethylamino) have been synthesized and their effect on the release of histamine from rat peritoneal mast cells measured. After chemical stimulation, (polymer 48/80), several compounds (i.e. 3b, 4a, 4b, 4d, 4g, 5a), produce inhibition two to three times higher (40--60%) than DSCG but this action is lower after preincubation. 4b (R(1)=Ph, R(2)=NHCH(2)Ph; 50--70% inhibition) and 5a (R(1)=H, R(2)=OMe; 50--55% inhibition) are the most active ones in both experiments. With ovoalbumin as stimulus, several pyrazolopyrimidines show inhibition similar to DSCG, the most active compounds being 6a--d (IC(50)=12--16 microM; R(1)=ribosetribenzoate, R(2)=methoxy and amino). Compounds 4e (R(1)=t-butyl, R(2)=OMe) and 4g (R(1)=t-butyl, R(2)=piperidino) are inducers of the release of histamine (60 and 150% increase). Compounds 4b and 4c showed cytotoxic activity (IC(50)=1 microg/mL) to HT-29 human colon cancer cells.

Synthesis and antiallergic activity of pyridothienopyrimidines

The synthesis of a series of pyridothienopyrimidines and their evaluation as inhibitors or inducers of the release of histamine from rat mast cells is reported. The activity was measured after immunological stimulation with ovoalbumin and chemical stimulation with polymer 48/80 and the drugs adryamicin and vinorelbine. The experiments were carried out with and without preincubation of the stimulus with the cells before addition of the drug. Several pyridothienopyrimidines show inhibitory IC50 values in the range 2-25 microM, indicating they are up to 100 times more potent than cromoglycate (DSCG) and 10 times greater than Ketotifen. Compound 9l is a potent inhibitor in all the conditions tested and shows IC50 = 9-25 microM. Pyridothienopyrimidines 4l and 9e are very strong inducers of histamine release in the immunological (4l, 170-230%) and chemical (9e, 100-150%) assays, respectively. Compounds 4l and 9i are cytotoxic in vitro (IC50 = 0.1-0.2 microgram/mL) against P-388, A-549, HT-29, and MEL-28 tumor cell lines.

A ready one-pot preparation for pyrrolo[2,1-f]-[1,2,4]triazine and pyrazolo[5,1-c]pyrimido[4,5-e]-[1,2,4]triazine derivatives

Abstract Several new 2,4-disubstituted pyrrolo[2,1- f ][1,2,4]triazines and pyrazolo[5,1- c ]-pyrimido[4,5- e ][1,2,4]triazines are easily obtained from the reaction of N , N -dimethyldichloromethyleniminium chloride with 1 -aminopyrrole- 2 -carbonitrile 1 and ethyl 4-amino-3-cyanopyrazolo[5,1- c ][1,2,4]triazine-8-carboxylate 6 , respectively.

Complexation and Extraction of PAHs to the Aqueous Phase with a Dinuclear PtII Diazapyrenium‐Based Metallacycle

New palladium and platinum metallacycles have been synthesized by reaction between a 2,7-diazapyrenium-based ligand and Pd(II) and Pt(II) complexes. The inclusion complexes between the metallacycles and polycyclic aromatic hydrocarbons (PAHs) in CD(3)NO(2) and D(2)O were studied by NMR spectroscopy. The structures of the inclusion complexes of the Pt metallacycle as host with pyrene, phenanthrene, and triphenylene were confirmed by single crystal X-ray crystallography. The association constants between the Pt metallacycle and the selected PAHs were determined in CH(3)CN following the characteristic charge-transfer band displayed in their UV/Vis absorption spectrum. Although in aqueous solution all the complexes showed a 1:1 stoichiometry, in CH(3)CN the Job plot indicated a 2:1 stoichiometry for complexes with triphenylene and benzo[a]pyrene. The estimated association constants in water correlate with the hydrophobicity of the PAH, indicating that hydrophobic forces play an important role in the complexation process.