New heterocyclic modifiers of oxidative drug metabolism. I. 6-Substituted-2-aminobenzothiazoles was written by Murray, Michael;Lacey, Ernest;Farrell, Geoffrey C.. And the article was included in Biochemical Pharmacology in 1986.Computed Properties of C11H14N2OS The following contents are mentioned in the article:
A series of 6-substituted-2-aminobenzothiazoles(2-AB) I (R = H, alkoxy, halo, etc.) was synthesized and evaluated as in vitro inhibitors of microsomal mixed-function oxidase [9038-14-6] activity (as aminopyrine N-demethylase [9037-69-8]) from phenobarbitone-induced rat liver. Using physiochem. parameters and multiple regression anal., QSAR was derived in which 82% of the data variance was accounted for in terms of the hydrophobic character of the inhibitor and the molar refractivity of the 2-AB 6-substituent. In contrast, literature equations derived from earlier studies with heterocyclic systems possessing nonpolar substituents underestimated by up to an order of magnitude the potency of the present compounds Kinetic studies revealed the 6-n-propoxy-2-AB, one of the more potent compounds, was a pure competitive inhibitor of aminopyrine N-demethylase activity (Ki = 60 μM from Dixon anal.), suggesting the the binding of substrate and inhibitor is mutually exclusive at the cytochrome P 450 [9035-51-2] active site. Binding studies indicated that most 2-AB derivatives elicited mixed-type I-reverse type I optical difference spectra in phenobarbitone-induced microsomes. The overlap of these components resulted in nonlinear double reciprocal plots of the spectral titrations and precluded the determination of binding parameters. In contrast, the more potent inhibitors (the 6-propoxy and 6-butoxy derivatives of 2-AB) were type I ligands with quite high affinity for ferric cytochrome P 450. Although no quant. relationship was apparent between inhibition and spectral binding affinity, a good correlation was observed between inhibition potency (I50) and the capacity of 10 2-AB derivatives to prevent substrate (aminoipyrine) binding to cytochrome P 450. These findings suggest that 2-AB derivatives may inhibit microsomal oxidation via a direct competitive effect on substrate binding to cytochrome P 450. The present study also demonstrates that substitution of heterocyclic systems with hydrophilic groups does not necessarily produce weak inhibitors of mixed-function oxidase activity, and that extrapolation of existing QSAR equations to new inhibitor series must be interpreted with caution. This study involved multiple reactions and reactants, such as 6-Butoxybenzo[d]thiazol-2-amine (cas: 14372-65-7Computed Properties of C11H14N2OS).
6-Butoxybenzo[d]thiazol-2-amine (cas: 14372-65-7) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Computed Properties of C11H14N2OS
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica