NAVEGLITAZAR (LY519818)

NAVEGLITAZAR

2(S)-Methoxy-3-[4-[3-(4-phenoxyphenoxy)propoxy]phenyl]propionic acid

476436-68-7

C25 H26 O6, 422.4703

• CCRIS 9448
• LY 519818
• LY 9818
• LY519818
• LY9818
• Naveglitazar
• UNII-Y995M7GM0G

http://clinicaltrials.gov/search/intervention=NAVEGLITAZAR

Naveglitazar, a peroxisome proliferator-activated receptor (PPAR) modulator, had been in phase II clinical trials for the once-daily oral treatment of type 2 diabetes, however, no recent development for this indication has been reported. The compound was originally discovered through an ongoing research collaboration between Lilly and Ligand, but, in 2006, Lilly discontinued the development program.

Naveglitazar [LY519818; benzenepropanoic acid, alpha-methoxy-4-[3-(4-phenoxyphenoxy)propoxy], (alpha-S)-] is a nonthiozolidinedione peroxisome proliferator-activated receptor alpha-gamma dual, gamma-dominant agonist that has shown glucose-lowering potential in animal models and in the clinic.

Studies have been conducted to characterize the disposition, metabolism, and excretion of naveglitazar in mice, rats, and monkeys after oral and/or i.v. bolus administration.

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2-Alkoxydihydrocinnamates as PPAR agonists. Activity modulation by the incorporation of phenoxy substituents.

Martín JA, Brooks DA, Prieto L, González R, Torrado A, Rojo I, López de Uralde B, Lamas C, Ferritto R, Dolores Martín-Ortega M, Agejas J, Parra F, Rizzo JR, Rhodes GA, Robey RL, Alt CA, Wendel SR, Zhang TY, Reifel-Miller A, Montrose-Rafizadeh C, Brozinick JT, Hawkins E, Misener EA, Briere DA, Ardecky R, Fraser JD, Warshawsky AM.

Bioorg Med Chem Lett. 2005 Jan 3;15(1):51-5.

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http://www.google.im/patents/US20050020684?cl=un

EXAMPLE 153

′2-Methoxy-3-{3-[3-(4-phenoxy-phenoxy)-propoxy]-phenyl}-propionic acid

The title compound was prepared from 3-(3-Hydroxy-phenyl)-2-methoxy-propionic acid methyl ester from Example 152, Step D with 4-(3-bromopropoxy)1-phenoxybenzene in a manner analogous as in Example 152, Step E. MS (ES) for C₂₅H₂₆O₆[M+NH₄]⁺: 440.2, [M+Na]⁺: 445.2. ¹H-NMR (CDCl₃, 200.15 MHz): 7.33-7.17 (m, 3H), 7.07-6.78 (m, 10H), 4.15 (dt, 4H, J=1.9, 6.2), 4.03 (dd, 1H, J=7.3, 4.3), 3.40 (s, 3H), 3.13 (dd, 1H, J=14.2, 4.6), 2.98 (dd, 1H, J=14.0, 7.5), 2.25 (qui, 2H, J=5.9)ppm.