313516-66-4

Off-White Solid

A cell-permeable chloro-nitro-benzamido compound that acts as a potent, specific, irreversible, and high-affinity antagonist of PPAR with a Ki of 1 nM. Displays >800-fold greater selectivity for PPAR over PPARa and PPARd (Ki = 0.85 and 1.8 ,

Potent and selective PPAR γ antagonist (IC 50 = 1 nM). Displays > 800-fold selectivity for PPAR γ over PPAR α and PPAR δ . In vitro, blocks transcriptional activity of PPAR γ and inhibits rosiglitazone-induced adipogenesis.

The peroxisome proliferator-activated receptor-γ (PPARγ) is the nuclear receptor responsible for transducing the therapeutic activity of the thiazolidinediones (TZDs). TZDs are a group of structurally related synthetic PPARγ receptor agonists with antidiabetic actions in vivo. There are many PPARγ agonists, including 15-deoxy-Δ^12,14-prostaglandin J₂ and azelaoyl PAF, which are naturally derived. However, only a few antagonists have been reported. T0070907 is a potent and selective antagonist of the human PPARγ with an apparent IC₅₀ of 1 nM for the binding inhibition of rosiglitazone, a reference TZD. T0070907 covalently binds to Cys³¹³ of PPARγ, inducing conformational changes that block the recruitment of transcriptional cofactors to the PPARγ/RXR heterodimer.

ChEBI: 2-chloro-5-nitro-N-pyridin-4-ylbenzamide is a carbonyl compound and an organohalogen compound.

T0070907 is very similar in structure and activity to the PPAR-γ antagonist GW9662. T0070907 is more potent and has higher selectivity for PPAR-γ over all other subtypes (about 800-fold) whereas GW9662 has been reported to have some PPAR-α agonist activity.

GENERAL STEPS: To a solution of 2-chloro-5-nitrobenzoic acid (0.500 g, 2.48 mmol) in dichloromethane (8.3 mL) was slowly added oxalyl chloride (0.239 mL, 2.73 mmol), followed by the addition of N,N-dimethylformamide (1 drop) as a catalyst. The reaction mixture was stirred at room temperature for 2 hours to complete the generation of the acyl chloride. Subsequently, triethylamine (0.691 mL, 4.96 mmol) was added to the reaction system as a base, followed by the slow addition of a dichloromethane (1 mL) solution of pyridin-4-amine (0.467 g, 4.96 mmol). The reaction mixture was continued to be stirred at room temperature for 16 h to ensure complete amidation reaction. Upon completion of the reaction, purification was carried out by fast column chromatography using 0-100% ethyl acetate/hexane gradient elution to afford the target compound 2-chloro-5-nitro-N-(pyridin-4-yl)benzamide as a brown solid (0.401 g, 58% yield). The structure of the product was analyzed by 1H NMR (400 MHz, DMSO-d6) δ 11.10 (s, 1H), 8.64-8.45 (m, 3H), 8.37 (dd, J = 8.9, 2.8 Hz, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.73-7.61 (m, 2H); 13C NMR (101 MHz, DMSO-d6) δ 163.67, 150.56, 146.14, 145.04, 136.95, 131.40, 126.06, 124.00, 113.68; ESI-MS m/z 278 ([M + H]+) confirmed.

Store at RT

[1] lee g, elwood f, mcnally j, weiszmann j, lindstrom m, amaral k, nakamura m, miao s, cao p, learned rm, chen jl, li y. t0070907, a selective ligand for peroxisome proliferator-activated receptor gamma, functions as an antagonist of biochemical and cellular activities. j biol chem. 2002 may 31;277(22):19649-57.