【药物名称】Valdecoxib, YM-974, SC-65872, Kudeq, Valdyn, Bextra
化学结构式(Chemical Structure):
参考文献No.30786
标题:Substd. isoxazoles for the treatment of inflammation
作者:Talley, J.J.; Brown, D.L.; Nagarajan, S.; Carter, J.S.; Weier, R.M.; Stealey, M.A.; Collins, P.W.; Seibert, K.; Graneto, M.J.; Xu, X.; Partis, R. (Pharmacia Corp.)
来源:EP 0809636; JP 1999503722; US 5633272; WO 9625405
合成路线图解说明:

Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol. Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III). Finally, treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

参考文献No.31900
标题:Substd. sulfonylphenylheterocycles as cyclooxygenase-2 and 5-lipoxygenase inhibitors
作者:Talley, J.J.; Sikorski, J.A.; Devadas, B.; Graneto, M.J.; Carter, J.S.; Norman, B.H.; Lu, H.-F.; Brown, D.L. (Pharmacia Corp.)
来源:EP 0828736; EP 0995747; US 5643933; WO 9638442
合成路线图解说明:

Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol. Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III). Finally, treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

参考文献No.39257
标题:Isoxazole cpds. as cyclooxygenase inhibitors
作者:Talley, J.J. (Pharmacia Corp.)
来源:US 5859257
合成路线图解说明:

Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol. Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III). Finally, treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

参考文献No.568398
标题:4-[5-Methyl-3-phenylisoxazol]4-yl]-benzenesulfonamide, valdecoxib: A potent and selective inhibitor of COX-2
作者:Talley, J.J.; Brown, D.L.; Carter, J.S.; Graneto, M.J.; Koboldt, C.M.; Masferrer, J.L.; Perkins, W.E.; Rogers, R.S.; Shaffer, A.F.; Zhang, Y.Y.; Zweifel, B.S.; Seibert, K.
来源:J Med Chem 2000,43(5),775
合成路线图解说明:

Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol. Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III). Finally, treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

参考文献No.610299
标题:Valdecoxib and Parecoxib Sodium
作者:Leeson, P.; Casta馿r, J.; Casta馿r, R.M.; Sorbera, L.A.
来源:Drugs Fut 2001,26(2),133
合成路线图解说明:

Deoxybenzoin (I) is converted to the corresponding oxime (II) by treatment with NH2OH稨Cl under basic conditions either with sodium acetate in aqueous ethanol or in toluene in presence of potassium hydroxide in absolute ethanol. Deprotonation of the oxime under nitrogen with 2eq of butyllithium in THF followed by cyclization in ethyl acetate or acetic anhydride affords isoxazoline (III). Finally, treatment of (III) with cold chlorosulfonic acid followed by reaction of the intermediate sulfonyl chloride with aqueous ammonia affords the desired product.

合成路线图解说明:

The acylation of 4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide, valdecoxib (I), with propionic anhydride (II) by means of TEA and DMAP in THF gives N-[4-(5-methyl-3-phenylisoxazol-4-yl)phenylsulfonyl]propionamide (III), which is then treated with NaOH in ethanol.

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