Chemistry:
Enasidenib is a first in class, a selective allosteric inhibitor of mutant isocitrate dehydrogenase-2 (IDH2) inhibitor discovered at Agios Pharmaceutical, Inc. in the United States of America. Recently, on 1 August 2017, Celgene Corporation and Agios Pharmaceutical in cooperation won the approval for Enasidenib under brand name IdhifaTm for the treatment of relapsed/refractory acute myeloid leukemia. it is a white to off-white crystalline, non hygroscopic powder existing in polymorphic form which is chemically known as 2-methyl-1-((4-(6-(trifluoromethyl)pyridin-2-yl)-6-((2-(trifluoromethyl)pyridin-4-yl)amino)-1,3,5-triazin2-yl)amino)propan-2-ol or 2-methyl-1-(4-(6-(trifluoromethyl)pyridin-2-yl)-6-(2-(trifluoromethyl)pyridin-4-ylamino)-1,3,5-triazin-2-yl …show more content…
The molecular mass of Enasidenib is 473.383 and monoisotopic mass 473.1398. It is practically insoluble in aqueous solution in physiological pH range 1.2 to 7.4, very little soluble in Water <1 mg/mL, soluble in DMSO 50 mg/mL and Ethanol 50 mg/mL, usually used in active form Enasidenib mesylate. IdhifaTm is available in two tablet oral dosage forms which are film-coated and contain 50mg (equivalent to 60 mg Enasidenib mesylate) and 100 mg (equivalent to 120 mg Enasidenib mesylate) with inert ingredients colloidal silicon dioxide, hydroxypropyl cellulose, hypromellose acetate succinate, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium lauryl sulphate, sodium starch glycolate, talc and titanium dioxide2.1
Synthesis of Enasidenib
Synthesis of Enasidenib is a complex process, consisting of six steps as depicted in Fig. 3. Step 1 the synthesis of 6-Trifluoromethyl-pyridine-2-carboxylic acid (2) from the starting material 2-trifluoromethyl-pyridine (1), dropwise addition into a reaction vessel containing diethyl ether, hexane, to which n- butyl lithium and dimethylaminoethanol was previously added dropwise under nitrogen atmosphere. The reaction mixture obtained is adjusted to pH with HCl and washed with …show more content…
Decreased R-2-HG levels reduce the anomalous histone hypermethylation, reduction in blasts count and restores differentiation function of myeloid cells, results increased the count of mature myeloid cells. Enasidenib's phase I/II results have shown a response rate of 37% in 159 patients having R/R-AML with complete remission of 27%. The action of enasidenib was identified as differentiation agent rather than cytotoxic thus producing mature fully functional neutrophils with conserved mutant IDH2 allele frequency in bone marrow blast of patients with mutant IDH2-AML along with negligible
Enasidenib is a first in class, a selective allosteric inhibitor of mutant isocitrate dehydrogenase-2 (IDH2) inhibitor discovered at Agios Pharmaceutical, Inc. in the United States of America. Recently, on 1 August 2017, Celgene Corporation and Agios Pharmaceutical in cooperation won the approval for Enasidenib under brand name IdhifaTm for the treatment of relapsed/refractory acute myeloid leukemia. it is a white to off-white crystalline, non hygroscopic powder existing in polymorphic form which is chemically known as 2-methyl-1-((4-(6-(trifluoromethyl)pyridin-2-yl)-6-((2-(trifluoromethyl)pyridin-4-yl)amino)-1,3,5-triazin2-yl)amino)propan-2-ol or 2-methyl-1-(4-(6-(trifluoromethyl)pyridin-2-yl)-6-(2-(trifluoromethyl)pyridin-4-ylamino)-1,3,5-triazin-2-yl …show more content…
The molecular mass of Enasidenib is 473.383 and monoisotopic mass 473.1398. It is practically insoluble in aqueous solution in physiological pH range 1.2 to 7.4, very little soluble in Water <1 mg/mL, soluble in DMSO 50 mg/mL and Ethanol 50 mg/mL, usually used in active form Enasidenib mesylate. IdhifaTm is available in two tablet oral dosage forms which are film-coated and contain 50mg (equivalent to 60 mg Enasidenib mesylate) and 100 mg (equivalent to 120 mg Enasidenib mesylate) with inert ingredients colloidal silicon dioxide, hydroxypropyl cellulose, hypromellose acetate succinate, iron oxide yellow, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polyvinyl alcohol, sodium lauryl sulphate, sodium starch glycolate, talc and titanium dioxide2.1
Synthesis of Enasidenib
Synthesis of Enasidenib is a complex process, consisting of six steps as depicted in Fig. 3. Step 1 the synthesis of 6-Trifluoromethyl-pyridine-2-carboxylic acid (2) from the starting material 2-trifluoromethyl-pyridine (1), dropwise addition into a reaction vessel containing diethyl ether, hexane, to which n- butyl lithium and dimethylaminoethanol was previously added dropwise under nitrogen atmosphere. The reaction mixture obtained is adjusted to pH with HCl and washed with …show more content…
Decreased R-2-HG levels reduce the anomalous histone hypermethylation, reduction in blasts count and restores differentiation function of myeloid cells, results increased the count of mature myeloid cells. Enasidenib's phase I/II results have shown a response rate of 37% in 159 patients having R/R-AML with complete remission of 27%. The action of enasidenib was identified as differentiation agent rather than cytotoxic thus producing mature fully functional neutrophils with conserved mutant IDH2 allele frequency in bone marrow blast of patients with mutant IDH2-AML along with negligible