Synthesis, spectral studies and biological profile of pyrazolines, isoxazoles, cyanopyridines having phenothiazine moiety

Several new 3,7-bis-fsubstituted benzalacetoaceL amidoj-phenothiazines 2a-j, 3,7-bi s[I'-N- H- / aceL y l-5'-ary l-2'­ pyrazolin-3' -yl acet::II11ido l-phenothiaz in es 3a-j , 4a-j, 3,7 obis-IS' -ary l-isoxazol-3' -y l-accta mido ]-phenothiaz in es Sa-j and 3,7-bi s- f2' -amino-3' -cyano-4' -ary l-py ridin-5' -yl-acetamido l-phcnothiazincs 6a-j havc been sylllhcs ised and screencd for an­ timicrobial activity. The products d isplay moderatc LO good or comparable acti vity with known standard drugs. Phenothi az in e deriv at iv es ' -6 playa vital ro le du e to biodynamic activity such as antihistaminic agent known as ' pyrala zote' , antiparkin son' s agent 7 known as ' Diparcol' and 2-amino-7-bromo-3-oxo-3-[H]­ phenothiazine hydrochl orid e as antitubercular agent8. Numerous reports have appeared in literature ascrib­ in g various types of bi ody namic properti es for heteroI· .. I' Y- II · I P - 13 d cyc IC nng VIZ. pyrazo In es , Isoxazo es - an cya nop yridin es '4- ' 5. In co ntinuati on of our work and in th e li ght of int erestin g biological activities, the pre­ sent note reports the sy nth es is of aryli denes, pyrazo li­ nes isoxazo les and cyanopy ridin es bearing ph enot hi ­ az ine moiety. 3,7-Diaminophenothiazine is reacted with ethyl acetoacetate to afford 3,7-b is-acetamid o phenothiaz­ in e 1 which on co nd ensatio n with aromatic aldehydes yield ed 3,7-bis-[substitued benza l acetoacetamido]­ phenothiazines 2a-j . Compounds 2a-j on chemose lec­ ti ve hetero cyc li sa tion with hydraz in e hydrate in ab ­ sence or presence of glacia l acet ic aci d affo rd ed 3,7 bis-[ I' -N-H-5' -aryl-2' -pyrazolin -3' -yl-aceta mido ]-phe­ nothi az in es 3a-j and 3,7 -bis-[ I' -N-acety l-5 ' -ary l-2'­ pyrazolin-3'-yl acetamido]-phenothiazines 4a-j re­ spec ti ve ly. Compounds 2a-j on cyc locondensa ti on with hydroxylam in e hydrochl orid e in presence of so­ dium acetate in ethanol afforded 3,7-bi s-[5'- aryl­ isoxazol-3'-y l acetam ido]-phenothi az in es 5a-j. 2a-j on chemoselective cyclisation with malononitrile in th e presence of am monium acetate gave 3,7 -bi s-[ 2'­ amin o-3' -cyano-4' -ary I pyridin-5' -y l ace tamido]­ phenothiazines 6a-j. The synthet ic seq uence is out­ lined in Scheme I. The stru cture of various co mpound s sy nth es ized are ass igned on the basis of element al anal yses, I R, PMR and mass spectr al data. The co mpounds were evalu ated for th eir antimi crob ial activit y.