Synthesis of some novel enzyme inhibitors and antibacterial agents derived from 5-(1-(4-tosyl)piperidin-4-yl)-1,3,4-oxadiazol-2-thiol

Tendo em vista a importância farmacologica da porcao 1,3,4-oxadiazol, sintetizou-se uma serie de novos derivados S-substituidos, 5a-h, de 5-(1-(4-tosi)piperidin-4-il)-1,3,4-oxadiazol-2-tiol (3). A reacao do cloreto de p-toluenossulfonila (a), com isonipecotato de (b) etila forneceu 1-(4-tosil)piperidin-4-carboxilato de metila (1), que foi, em seguida, transformado em 1-(4-tosil)piperidin-4-carbo-hidrazida (2) por reacao com hidrato de hidrazina em metanol. O composto 2 foi submetido a refluxo com CS2 na presenca de KOH para se obter 5-(1-(4-tosil)piperidin-4-il)-1,3,4-oxadiazol-2-tiol (3). Os compostos desejados, 5a-h, foram obtidos por agitacao de 3 com haletos de aralquila, 4a-h, em DMF, na presenca de NaH. As estruturas dos compostos sintetizados foram elucidadas atraves de analise dos espectros de 1H-MNR, IR e EI-MS. Estes compostos foram, ainda, avaliados quanto a inibicao das enzimas lipoxigenase e alfa-glucosidase, juntamente com a atividade antibacteriana contra bacterias Gram positivas e Gram negativas.

[1]  M. El-Gamal,et al.  Synthesis and broad-spectrum antiproliferative activity of diarylamides and diarylureas possessing 1,3,4-oxadiazole derivatives. , 2015, Bioorganic & medicinal chemistry letters.

[2]  D. Hu,et al.  Antibacterial activities against rice bacterial leaf blight and tomato bacterial wilt of 2-mercapto-5-substituted-1,3,4-oxadiazole/thiadiazole derivatives. , 2015, Bioorganic & medicinal chemistry letters.

[3]  Xiaoyun Fu,et al.  Synthesis and antitumor activities of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety. , 2014, Bioorganic & medicinal chemistry letters.

[4]  K. Khan,et al.  SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL SCREENING OF VARIOUS N-SUBSTITUTED DERIVATIVES OF SULFONAMIDES , 2011 .

[5]  K. Shah,et al.  An efficient synthesis and biological study of novel indolyl-1,3,4-oxadiazoles as potent anticancer agents. , 2009, Bioorganic & medicinal chemistry letters.

[6]  Thiam Hong Ang,et al.  Synthesis and the biological evaluation of 2-benzenesulfonylalkyl-5-substituted-sulfanyl-[1,3,4]-oxadiazoles as potential anti-hepatitis B virus agents. , 2006, Antiviral research.

[7]  B. Herradón,et al.  Short syntheses of (S)-pipecolic acid, (R)-coniine, and (S)-δ-coniceine using biocatalytically-generated chiral building blocks , 1998 .

[8]  N. Mahfouz,et al.  Design, synthesis and antiinflammatory activity of some 1,3,4-oxadiazole derivatives. , 1997, European journal of medicinal chemistry.

[9]  B. Adger,et al.  Stereospecific Synthesis of the Anaesthetic Levobupivacaine. , 1996 .

[10]  R. Tremblay,et al.  P-Nitrophenol-alpha-D-glucopyranoside as substrate for measurement of maltase activity in human semen. , 1978, Clinical chemistry.

[11]  S. Rasool,et al.  Synthesis and Biological Screening of S-Substituted Derivatives of 5-{1-[(4-Chlorophenyl)sulfonyl]-3-piperidinyl}-1,3,4-oxadiazol-2-yl Sulfide , 2015 .

[12]  K. Khan,et al.  Synthesis of Potent Antibacterial Agents Derived from 5-(1-(Phenylsulfonyl)piperidin-4-yl)-1,3,4-oxadiazol-2-thiol , 2014 .

[13]  J. Jayabharathi,et al.  IN VITRO ANTIOXIDANT ACTIVITY OF HINDERED PIPERIDONE DERIVATIVES , 2011 .

[14]  Pradeep Kumar,et al.  Syntheses, Evaluation and Characterization of Some 1, 3, 4-Oxadiazoles as Antimicrobial Agents , 2009 .

[15]  G. K. Rao,et al.  Synthesis, Antibacterial Activity of 2,4-Disubstituted Oxazoles and Thiazoles as Bioisosteres , 2009 .

[16]  S. Baylac,et al.  Inhibition of 5-lipoxygenase by essential oils and other natural fragrant extracts , 2003 .