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【结 构 式】 
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【药物名称】 【化学名称】3-[4-[3,3-Bis(biphenyl-4-yl)-2-propen-1-yloxy]phenyl]-2(S)-ethoxypropionic acid 【CA登记号】303110-77-2 【 分 子 式 】C38H34O4 【 分 子 量 】554.69228 |
【开发单位】Novo Nordisk (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, PPARalpha Agonists, PPARdelta Agonists, PPARgamma Agonists |
合成路线1
The Horner-Emmons condensation of 4,4'-dibromobenzophenone (I) with triethyl phosphonoacetate leads to the 3,3-diarylpropenoate (II). Ester (II) is subsequently reduced to the allylic alcohol (III) employing DIBAL in cold THF. Suzuki coupling of aryl bromide (III) with phenylboronic acid (IV) furnishes 3,3-bis-(biphenyl-4-yl)-2-propen-1-ol (V). Coupling of allylic alcohol (V) with (S) ethyl 2-ethoxy-3-(4-hydroxyphenyl)propionate (VI) by means of 1,1'-(azodicarbonyl)dipiperidine (ADDP) and tributylphosphine under Mitsunobu conditions gives rise to the ether adduct (VII). Finally, saponification of the ethyl ester group of (VII) provides the target carboxylic acid.
| 【1】 Mogensen, J.P.; Jeppesen, L.; Bury, P.S.; Pettersson, I.; Fleckner, J.; Nehlin, J.; Frederiksen, K.S.; Albrektsen, T.; Din, N.; Mortensen, S.B.; Svensson, L.A.; Wasserman, K.; Wulff, E.M.; Ynddal, L.; Sauerberg, P.; Design and synthesis of novel PPARalpha/gamma/delta triple activators using a known PPARalpha/gamma dual activator as structural template. Bioorg Med Chem Lett 2003, 13, 2, 257. |
| 【2】 Sauerberg, P.; Jeppesen, L.; Bury, P.S.; Murray, A.; Pettersson, I. (Novo Nordisk A/S); New cpds., their preparation and use. EP 1171414; JP 2002542218; WO 0063153 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 34447 | bis(4-bromophenyl)methanone | 3988-03-2 | C13H8Br2O | 详情 | 详情 |
| (II) | 63223 | ethyl 3,3-bis(4-bromophenyl)acrylate | C17H14Br2O2 | 详情 | 详情 | |
| (III) | 63224 | 3,3-bis(4-bromophenyl)-2-propen-1-ol | C15H12Br2O | 详情 | 详情 | |
| (IV) | 16593 | Phenylboronic acid；Benzeneboronic acid;Phenylboron dihydroxide | 98-80-6 | C6H7BO2 | 详情 | 详情 |
| (V) | 63225 | 3,3-di[1,1'-biphenyl]-4-yl-2-propen-1-ol | C27H22O | 详情 | 详情 | |
| (VI) | 50418 | ethyl (2S)-2-ethoxy-3-(4-hydroxyphenyl)propanoate | C13H18O4 | 详情 | 详情 | |
| (VII) | 63226 | ethyl (2S)-3-{4-[(3,3-di[1,1'-biphenyl]-4-yl-2-propenyl)oxy]phenyl}-2-ethoxypropanoate | C40H38O4 | 详情 | 详情 |