title: Novel serine protease dipeptidyl peptidase IV inhibitor: alogliptin.
abstract: Alogliptin (codenamed SYR-322) is a recently approved anti-diabetic drug in Japan, which has been under clinical development phase III in USA and Europe. Alogliptin has been developed by Takeda under the brand name "Nesina". Alogliptin is a highly selective ( > 10,000-time selectivity, potent, reversible and durable serine protease dipeptidyl peptidase IV enzyme is compared to DPP-8 and DPP-9) inhibitor, which has been developed as an alternative second-line to metformin in place of a sulphonylurea. Alogliptin has been observed to increase and prolong the action of incretin hormone by inhibiting the DPP-IV enzyme activity. Alogliptin has been observed to well absorb and show low plasma protein binding, which displays slow-binding properties to DPP-IV enzyme. The X-ray crystallography studies have been revealed that Alogliptin binds to DPP-IV active site by non-covalently and provides sustained reduction of plasma DPP-IV activity as well as lowering of blood glucose, in drug-naive patients with T2DM and inadequate glycemic control, once daily oral dosing regimen with varying levels of doses ranging from 25-800 mg. Alogliptin is approved as monotherapy and in combination with alpha-glucosidase & thiazolidinediones. The 26 week clinical study of Alogliptin revealed that Alogliptin doesn't increase the weight and well tolerated. In the present review, we have tried to cover biology of DPP-IV, molecular chemistry, chemical characterization, crystal polymorphic information, interaction studies, commercial synthesis, current patent status, adverse effects and clinical status of Alogliptin giving emphasis on the medicinal chemistry aspect.
authors.affiliation: Department of Chemistry, Shrimant Madhavrao Scindia, Government Model Science College, Jhansi Road, Gwalior, Madhya Pradesh, India, PIN No. 474001. riteshagrawalip@gmail.com
authors.forename: Ritesh
authors.initials: R
authors.lastname: Agrawal
authors.forename: Radhe Shyam
authors.initials: RS
authors.lastname: Bahare
authors.forename: Pratima
authors.initials: P
authors.lastname: Jain
authors.forename: Subodh Narayan
authors.initials: SN
authors.lastname: Dikshit
authors.forename: Swastika
authors.initials: S
authors.lastname: Ganguly
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D010880:Piperidines / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D014498:Uracil / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D010880:Piperidines; D014498:Uracil; D018819:Dipeptidyl Peptidase 4; C520853:alogliptin