Synthesis of spiro[chroman-2,4'-piperidin]-4-one derivatives as acetyl-CoA carboxylase inhibitors.
Various spiro[chroman-2,4'-piperidin]-4-one derivatives (38a-m and 43a-j) have been designed, synthesized and evaluated for in vitro acetyl-CoA carboxylase (ACC) inhibitory activity. Several compounds have shown ACC inhibitory activity in low nanomolar range. Compound 38j reduced the respiratory quotient (RQ) in C57BL/6J mice indicating increase in whole body fat oxidation even in the presence of high carbohydrate diet. Structure-activity relationship (SAR) has been discussed.
Shinde
Pundlik
P
Medicinal Chemistry, Torrent Research Centre, Torrent Pharmaceuticals Ltd, PO Bhat, Gandhinagar 382428, Gujarat, India.
Srivastava
Sanjay K
SK
Odedara
Rajendra
R
Tuli
Davinder
D
Munshi
Siralee
S
Patel
Jitendra
J
Zambad
Shitalkumar P
SP
Sonawane
Rajesh
R
Gupta
Ramesh C
RC
Chauthaiwale
Vijay
V
Dutt
Chaitanya
C
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D002241:Carbohydrates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002839:Chromans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D020128:Inhibitory Concentration 50; D051379:Mice; D008810:Mice, Inbred C57BL; D008956:Models, Chemical; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry
D002241:Carbohydrates; D002839:Chromans; D010880:Piperidines; D013141:Spiro Compounds; C539994:spiro(chroman-2,4'-piperidin)-4-one; D000255:Adenosine Triphosphate; D014508:Urea; D000103:Acetyl-CoA Carboxylase