ABSTRACT

Novel bicyclic derivatives have been synthesized. The solubility of drug-like substances in phosphate buffer pH 7.4 has been measured within the range of (9.02 10 5 to 1.05 10 4) mol/l. The relationship between the chemical nature and the structure of the aryl substituents and the solubility parameter was investigated. The fusion temperatures, enthalpies and entropies have been determined experimentally. The influence of thermophysical characteristics and lipophilicity on the solubility was studied using regression analysis. The calculations by the solubility/lipophilicity equation showed an overall improvement of the predictions equal to 0.5 log units. It was concluded that the solvation has a considerable influence on the solubility of the compounds under consideration. It was also determined that the alkyl- and halogen-derivatives solubility values correlate with HYBOT descriptors characterizing the (donor + acceptor) properties of the substances. The thermodynamic parameters of the solubility process were calculated using the temperature dependences. The study also revealed that the solubility of the bicyclic compounds is characterized by high endothermicity of the processes and negative entropies.

Compounds

#	Formula	Name
1	C14H18N2S	(4-methylphenyl)-[3-thia-1-aza-bicyclo[3.3.1]non-2-ylidene]amine
2	C16H22N2S	(4-isopropylphenyl)-[3-thia-1-aza-bicyclo[3.3.1]non-2-ylidene]amine
3	C13H15FN2S	(4-fluorophenyl)-[3-thia-1-aza-bicyclo[3.3.1]non-2-ylidene]amine
4	C14H15F3N2S	(4-(trifluoromethyl)phenyl)-[3-thia-1-aza-bicyclo[3.3.1]non-2-ylidene]amine
5	C15H18N2OS	(4-acetylphenyl)-[3-thia-1-aza-bicyclo[3.3.1]non-2-ylidene]amine
6	C14H15N3S	(4-cyanophenyl)-[3-thia-1-aza-bicyclo[3.3.1]non-2-ylidene]amine

Datasets

The table above is generated from the ThermoML associated json file (link above). POMD and RXND refer to PureOrMixture and Reaction Datasets. The compound numbers are included in properties, variables, and phases, if specificied; the numbers refer to the table of compounds on the left.
Type	Compound-#	Property	Phase	Method	#Points
POMD	1	Normal melting temperature, K ; Crystal	Crystal Liquid Air at 1 atmosphere	DTA	1
POMD	1	Molar enthalpy of transition or fusion, kJ/mol ; Crystal	Crystal Liquid Air at 1 atmosphere	DSC	1
POMD	2	Normal melting temperature, K ; Crystal	Crystal Liquid Air at 1 atmosphere	DTA	1
POMD	2	Molar enthalpy of transition or fusion, kJ/mol ; Crystal	Crystal Liquid Air at 1 atmosphere	DSC	1
POMD	3	Normal melting temperature, K ; Crystal	Crystal Liquid Air at 1 atmosphere	DTA	1
POMD	3	Molar enthalpy of transition or fusion, kJ/mol ; Crystal	Crystal Liquid Air at 1 atmosphere	DSC	1
POMD	4	Normal melting temperature, K ; Crystal	Crystal Liquid Air at 1 atmosphere	DTA	1
POMD	4	Molar enthalpy of transition or fusion, kJ/mol ; Crystal	Crystal Liquid Air at 1 atmosphere	DSC	1
POMD	5	Normal melting temperature, K ; Crystal	Crystal Liquid Air at 1 atmosphere	DTA	1
POMD	5	Molar enthalpy of transition or fusion, kJ/mol ; Crystal	Crystal Liquid Air at 1 atmosphere	DSC	1
POMD	6	Normal melting temperature, K ; Crystal	Crystal Liquid Air at 1 atmosphere	DTA	1
POMD	6	Molar enthalpy of transition or fusion, kJ/mol ; Crystal	Crystal Liquid Air at 1 atmosphere	DSC	1

Thermodynamics Research Center / ThermoML | Journal of Chemical Thermodynamics

Effect of the structure, solid state and lipophilicity on the solubility of novel bicyclic derivatives

Blokhina, S. V.[Svetlana V.], Olkhovich, M. V.[Marina V.], Sharapova, A. V.[Angelica V.], Volkova, T. V.[Tatyana V.], Proshin, A. N.[Alexey N.], Perlovich, G. L.[German L.]

ABSTRACT