Synthesis and therapeutic evaluation of pyridyl based novel mTOR inhibitors.
A series of novel cyanopyridyl based molecules (1-14) were designed, synthesized and probed for inhibition of mammalian target of rapamycin (mTOR) activity. Compound 14 was found to be a potent inhibitor of mTOR activity as assessed by enzyme-linked immunoassays and Western blot analysis. Most importantly, systemic application (intraperitoneal; ip) of compound 14 significantly suppressed macroscopic and histological abnormalities associated with chemically-induced murine colitis.
Deore
Vijaykumar
V
Department of Medicinal Chemistry, Piramal Life Sciences, 1-Nirlon Complex, Goregaon (E), Mumbai, India.
Yewalkar
Nilambari
N
Bhatia
Dimple
D
Desai
Nikesh
N
Gupte
Ravindra D
RD
Dadarkar
Shruta S
SS
Jadhav
Mahesh G
MG
Tannu
Aditi A
AA
Bhatt
Pooja
P
Nemmani
Kumar V S
KV
Vishwakarma
Ram A
RA
Sharma
Somesh
S
Roychowdhury
Abhijit
A
Dagia
Nilesh M
NM
Bhonde
Mandar R
MR
Kumar
Sanjay
S
D000178:Acrylamides / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D045744:Cell Line, Tumor; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009570:Nitriles / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011494:Protein Kinases / Q000737:chemistry / Q000378:metabolism*; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases
D000178:Acrylamides; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases