BIOISOSTERIC SYNTHESIS AND U.V. SPECTRAL BEHAVIOUR OF TETRA-AZO FUSED RING PYRAZOLO-TETRAZINE AND PYRAZOLO-TRIAZINE MOIETIES HAVING VARIABLE HETERO ATOMS OXYGEN/SULFUR/NITROGEN POTENTIAL FOR PARTITION COEFFICIENT
|Title||BIOISOSTERIC SYNTHESIS AND U.V. SPECTRAL BEHAVIOUR OF TETRA-AZO FUSED RING PYRAZOLO-TETRAZINE AND PYRAZOLO-TRIAZINE MOIETIES HAVING VARIABLE HETERO ATOMS OXYGEN/SULFUR/NITROGEN POTENTIAL FOR PARTITION COEFFICIENT|
|Publication Type||Conference Proceedings|
|Year of Conference||2017|
|Authors||, Sen S. Patel and, &|
|Conference Name||The Ramanbhai Foundation 8th International Symposium on Current Trends in Pharmaceutical Sciences|
Solubility of any organic compounds in water or organic solvent depend on the presence of functional groups having electronegative atoms like oxygen, nitrogen and sulfur either in single entity or as a functional groups. The electronegativity of these atoms is as follows O: 3.44, N: 3.04, S: 2.58 which can act as heteroatoms in heterocyclic ring also either in fused ring or single ring. Solubility profile is determined by logarithmic partition coefficient values (logP) which is the ratio of solubility of compound in organic phase and water phase. The synthesized compounds are of two series: pyrazolo-tetrazine & pyrazolo-triazine moieties having variable hetero atoms: Oxygen/Sulfur/Nitrogen which produce compounds. In pyrazolo-tetrazine ring system all four nitrogen atoms are in ring and three nitrogen atoms and subsequently placed serially whereas in pyrazolo-triazine three nitrogen atoms are in ring but in alternate positions separated by carbon atom so logP profile of pyrazolo-triazines are higher than pyrazolo-tetrazines [pyrazolo-triazines>pyrazolo-tetrazines]
The three electronegative elements are O: 3.44, N: 3.04, S: 2.58 as hetero atoms are in active part to make fused ring heterocyclic moiety of five membered with six membered due to urea (X=O), thiourea (X=S) and guanidine (X=NH). Oxygen and sulfur both have two lone pair of electrons but electronegativity of O>S and due to less electronegativity of sulfur the logP profile of sulfur derivative becomes higher than oxygen derivatives whereas in nitrogen there is one lone pair of electrons so the logP profile of nitrogen becomes more less.
(A) (B) (C)
(D) (E) (F)
Both of series of 6-methyl-4-phenyl-8H-pyrazolo[1,2-a][1,2,3,5]tetrazine [A-C] and 7-methyl-4,6-diphenylpyrazolo[1,5-a][1,3,5]triazin [D-F] having same hetero atoms oxgen/sulfur/nitrogen shows different logP schedule due to the presence of one phenyl ring in tetrazine and two phenyl rings in triazine nucleus: pyrazolo-triazines>pyrazolo-tetrazines and the partition coefficient of previous one is lesser than former series. logP of urea derivative of pyrazolo-tetrazine is less than urea derivative of the same ring, logP of thiourea derivative is higher than urea derivative of pyrazolo-tetrazine and logP of guanidine derivative is lesser than both urea and thiourea derivatives of pyrazolo-tetrazine. Pyrazolo-triazine series show higher values than pyrazolo-tetrazine series for all three cases of urea/thiourea/guanidine derivatives due to variable electronegativity.
Keywords: pyrazolo-tetrazines, pyrazolo-triazines, logP