Selective hydroboration of dieneamines. Formation of hydroxyalkylphenothiazines as MDR modulators.
N-dienylphenothiazines synthesized from tetrazolo[1,5-a]pyridinium salts by treatment with phenothiazine were subjected to catalytic hydrogenation to yield N-butylphenothiazines, whereas transformation of these dienes with borane dimethyl sulfide (BH(3) × Me(2)S) resulted in selective hydroboration of one double bond and full reduction of the other double bond to give 2-hydroxybutylphenothiazines. Position of the hydroxyl group was supported by NMR spectroscopy and verified by X-ray analysis. Comparison of MDR modulatory activity of the new derivatives revealed that the hydroxybutyl compounds are promising candidates for development of novel MDR inhibitors.
Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Pusztaszeri út 59-67, H-1025 Budapest, Hungary.
Daniella
D
Takács
Ildikó
I
Nagy
Petra
P
Bombicz
Orsolya
O
Egyed
Katalin
K
Jemnitz
Zsuzsanna
Z
Riedl
József
J
Molnár
Leonard
L
Amaral
György
G
Hajós
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000588:Amines / Q000737:chemistry*; D000818:Animals; D001880:Boranes / Q000737:chemistry; D002478:Cells, Cultured; D018360:Crystallography, X-Ray; D018432:Drug Resistance, Multiple / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects; D008297:Male; D008968:Molecular Conformation; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000588:Amines; D001880:Boranes; D010640:Phenothiazines; D011743:Pyrimidines; C550393:tetrazolo(1,5-a)pyrimidine; C031637:phenothiazine