Chemistry of pyridoxine in drug design

Russian Chemical Bulletin - Pyridoxine and its derivatives, pyridoxamine and pyridoxal, are the three main forms of vitamin B6, which play exceptionally important biological roles in living...     

Synthesis and antiadrenergic properties of β-substituted alcohols based on 6-hydroxymethylpyridoxine

An approach to the synthesis of epoxides based on 6-hydroxymethylpyridoxine acetals was developed. The epoxides obtained were involved in the ring opening reactions by nitrogen-, oxygen-, and sulfur-containing nucleophiles. Cytotoxicity and antiadrenergic properties of some synthesized compounds were studied on the models in situ and in vivo.     

Reactions of 4,5-diamino-3-methyl-1-phenylpyrazole with diarylideneacetones

The reaction of 4,5-diamino-3-methyl-1-phenylpyrazole with dibenzylideneacetone and its 4,4-derivatives has been studied; the reactions lead to aromatic 1H-2,3-dihydropyrazolo[5,4-b]1,5-diazepine derivatives. The reaction pathway has also been identified.Translated from Khimiya Geterotsiklicheskikh Sodinenii, No. 11, pp. 1563–1567, November, 1987.     

Synthesis and antitumor activity of pyridoxine monoalkenyl derivatives

A convenient method for the synthesis of pyridoxine alkenyl derivatives by the Wittig reaction of [(2,8-dimethyl-4H-[1,3]dioxino[4,5-c]pyridin-5-yl)methyl]triphenylphosphonium chloride with aldehydes was suggested. Some of the compounds obtained exhibit antitumor activity in vitro.     

Substituted 1,10b-dihydro-5H-pyrazolo[1,5-c]-1,3-benzoxazines

A study was made of the reaction of 3-phenyl-5-(2-hydroxyphenyl)-1H-2-pyrazoline with various aldehydes and ketones, which results in the formation of derivatives of 1,10b-dihydro-5H-pyrazolo[1,5-c]-1,3-benzoxazine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1131–1136, August, 1991.     

Antioxidative vs cytotoxic activities of organotin complexes bearing 2,6‐di‐tert‐butylphenol moieties

Two series of organotin(IV) complexes with Sn–S bonds on the base of 2,6‐di‐tert‐butyl‐4‐mercaptophenol ( L ¹ SH ) of formulae Me₂Sn(L¹S)₂ ( 1 ); Et₂Sn(L¹S)₂ ( 2 ); Bu₂Sn(L¹S)₂ ( 3 ); Ph ₂ Sn(L¹S)₂ ( 4 ); (L¹)₂Sn(L¹S)₂ ( 5 ); Me₃Sn(L¹S) ( 6 ); Ph₃Sn(L¹S) ( 7 ) (L¹ = 3,5‐di‐tert‐butyl‐4‐hydroxyphenyl), together with the new ones [Me₃SnCl(L²)] ( 8 ), [Me₂SnCl₂(L²)₂] ( 9 ) ( L ²  = 2‐(N‐3′,5′‐di‐tert‐butyl‐4′‐hydroxyphenyl)‐iminomethylphenol) were used to study their antioxidant and cytotoxic activity. Novel complexes 8 , 9 of Me_nSnCl_4 ? n (n = 3, 2) with Schiff base were synthesized and characterized by ¹H, ¹³C NMR, IR and elemental analysis. The crystal structures of compounds 8 and 9 were determined by X‐ray diffraction analysis. The distorted tetrahedral geometry around the Sn center in the monocrystals of 8 was revealed, the Schiff base is coordinated to the tin(IV) atom by electrostatic interaction and formation of short contact Sn–O 2.805 Å. In the case of complex 9 the distorted octahedron coordination of Sn atom is formed. The antioxidant activity of compounds as radical scavengers and reducing agents was proved spectrophotometrically in tests with stable radical DPPH, reduction of Cu²⁺ (CUPRAC method) and interaction with superoxide radical‐anion. Moreover, compounds have been screened for in vitro cytotoxicity on eight human cancer cell lines. A high activity against all cell lines with IC₅₀ values 60–160 nM was determined for the triphenyltin complex 7 , while the introduction of Schiff base decreased the cytotoxicity of the complexes. The influence on mitochondrial potential and mitochondrial permeability for the compounds 8 and 9 has been studied. It is shown that studied complexes depolarize the mitochondria but don't influence the calcium‐induced mitochondrial permeability transition.     

Hammett constants of the pyrroline-2, 5-dione ring

The electronic effect of the pyrroline-2,5-dione ring on the benzene ring in the case of N-aryl compounds is close to the effect exerted by halogens. The overall electron-acceptor effect depends markedly on the nature of the solvent. The electron-donor effect of conjugation is small.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 906–910, July, 1976.     

Synthesis and biological activity of quaternary phosphonium salts based on 3-hydroxypyridine and 4-deoxypyridoxine

Methods for the synthesis of quaternary phosphonium salts based on 3-hydroxypyridine and 4-deoxypyridoxine were developed. Some of obtained compounds possess high antibacterial and antitumor activity in vitro.     

Heterocyclization of Amidophenacylation Products of Uracil

When uracil is reacted with benzoylamino(chloro)acetophenone, we obtain two amidophenacylation products depending on the condensation conditions. The first product contains an amidophenacyl moiety at the N¹ center, and in the second product two such moieties are located at the N¹ and N³ centers of the uracil. Treatment of these accessible uracil derivatives with phosphorus oxychloride, thionyl chloride, or phosphorus pentasulfide leads to cyclization of the amidophenacyl side group, which is used to synthesize a number of modified pyrimidine bases with 2,5-diphenyloxazole or 2,5-diphenylthiazole residues.