GW-1929, -Drug Synthesis Database

【结构式】

【药物名称】GW-1929

【化学名称】2(S)-(2-Benzoylanilino)-3-[4-[2-[N-methyl-N-(2-pyridinyl)amino]ethoxy]phenyl]propionic acid
　　　　　　N-(2-Benzoyphenyl)-O-[2-[N-methyl-N-(2-pyridinyl)amino]ethyl]-L-tyrosine

【CA登记号】196808-24-9, 219653-30-2 (D-isomer), 196808-23-8 (racemate)

【分子式】C₃₀H₂₉N₃O₄

【分子量】495.58333

【开发单位】GlaxoSmithKline (Originator)

【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Lipoprotein Disorders, Treatment of , METABOLIC DRUGS, Type 2 Diabetes Mellitus, Agents for, Insulin Sensitizers, PPARgamma Agonists

合成路线1

The 2-aminobenzophenone derivative (III) was prepared by condensation of L-tyrosine methyl ester (I) with 2-benzoylcyclohexanone (II) in refluxing anisole, with concomitant dehydrogenation in the presence of Pd/C. Subsequent Mitsunobu coupling of (III) with 2-(N-Boc-N-methylamino)ethanol (V), prepared from aminoalcohol (IV) and Boc2O, afforded the Boc-protected aminoethyl ether (VI). After removal of the Boc group of (VI) by treatment with trifluoroacetic acid, condensation of the resulting secondary amine (VII) with 2-fluoropyridine (VIII) yielded the 2-aminopyridine derivative (IX). Finally, the methyl ester group of (IX) was hydrolyzed to the title carboxylic acid using LiOH.

参考文献中间体

【1】 N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel serieis of potent antihyperglycemic and antihyperlipidemic agents. J Med Chem 1998, 41, 25, 5020.
【2】 Willson, T.M.; Mook, R.A. Jr.; Kaldor, I.; Henke, B.R.; Deaton, D.N.; Collins, J.L.; Cobb, J.E.; Brackeen, M.; Sharp, M.J.; O'Callaghan, J.M.; Erickson, G.A.; Boswell, G.E. (Glaxo Wellcome plc); Substd. 4-hydroxy-phenylalkanoic acid derivs. with agonist activity to PPAR-gamma. EP 0888317; JP 2000507216; WO 9731907 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	23767	Methoxybenzene; Methyl phenyl ether; Anisole	100-66-3	C₇H₈O	详情	详情
(I)	21431	methyl (2S)-2-amino-3-(4-hydroxyphenyl)propanoate	1080-06-4	C₁₀H₁₃NO₃	详情	详情
(II)	21432	2-benzoylcyclohexanone	3580-38-9	C₁₃H₁₄O₂	详情	详情
(III)	21434	methyl (2S)-2-(2-benzoylanilino)-3-(4-hydroxyphenyl)propanoate		C₂₃H₂₁NO₄	详情	详情
(IV)	13324	2-Methylaminoethanol; 2-(Methylamino)-1-ethanol	109-83-1	C₃H₉NO	详情	详情
(V)	34509	tert-butyl 2-hydroxyethyl(methyl)carbamate		C₈H₁₇NO₃	详情	详情
(VI)	34510	methyl (2S)-2-(2-benzoylanilino)-3-(4-[2-[(tert-butoxycarbonyl)(methyl)amino]ethoxy]phenyl)propanoate		C₃₁H₃₆N₂O₆	详情	详情
(VII)	34511	methyl (2S)-2-(2-benzoylanilino)-3-[4-[2-(methylamino)ethoxy]phenyl]propanoate		C₂₆H₂₈N₂O₄	详情	详情
(VIII)	34512	2-fluoropyridine	372-48-5	C₅H₄FN	详情	详情
(IX)	34513	methyl (2S)-2-(2-benzoylanilino)-3-(4-[2-[methyl(2-pyridinyl)amino]ethoxy]phenyl)propanoate		C₃₁H₃₁N₃O₄	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)