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【结 构 式】 
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【药物名称】NNC-57-0734 【化学名称】1-[4-Amino-2-(4-chlorophenylamino)thiazol-5-yl]-1-[3-(benzyloxy)phenyl]methanone 【CA登记号】 【 分 子 式 】C23H18ClN3O2S 【 分 子 量 】435.93581 |
【开发单位】Novo Nordisk (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS, Type 2 Diabetes Mellitus, Agents for, Glycogen Synthase Kinase 3 (GSK-3) Inhibitors |
合成路线1
The reaction of N1-amidino-N3-(4-chlorophenyl)thiourea (I) with 3-(benzyloxy)phenacyl bromide (II) in ethanol/acetone gives the N1-amidino-S-[2-(3-benzyloxyphenyl)-2-oxoethyl]-N3-(4-chlorophenyl)isothiourea (III), which without isolation is cyclized to the target aminothiazole by means of TEA.
| 【1】 Sorensen, A.R.; Engelhardt, S.; Kurtzhals, P.; Urso, B.; Bowler, A.N.; 2,4-Diaminothiazoles: A novel class of glycogen synthase kinase-3 (GSK-3) inhibitors. 11th RSC-SCI Med Chem Symp (Sept 9 2001, Cambridge) 2001, Abst P20. |
| 【2】 Olesen, P.H.; Kurtzhals, P.; Bowler, A.N.; Soerensen, A.R.; Worsaae, H.; Hansen, B.F. (Novo Nordisk A/S); 2,4-Diaminothiazole derivs.. WO 0156567 . |
| 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) | 53540 | 1-[({[amino(imino)methyl]amino}carbothioyl)amino]-4-chlorobenzene | n/a | C8H9ClN4S | 详情 | 详情 |
| (II) | 53541 | 1-[3-(benzyloxy)phenyl]-2-bromo-1-ethanone | n/a | C15H13BrO2 | 详情 | 详情 |
| (III) | 53544 | N-[(Z)-({2-[3-(benzyloxy)phenyl]-2-oxoethyl}sulfanyl)(4-chloroanilino)methylidene]guanidine | n/a | C23H21ClN4O2S | 详情 | 详情 |
合成路线2
The reaction of 4-chloroaniline (I) with di(2-pyridyl)thione (DPT) gives the corresponding isothiocyanate (II), which is condensed with cyanamide (III) and 2-bromo-1-(3-benzyloxyphenyl)ethanone (IV) by means of NaOMe to yield the adduct (V). This compound, without isolation, cyclizes to the target thiazole.
| 【1】 Sorensen, A.R.; Engelhardt, S.; Kurtzhals, P.; Urso, B.; Bowler, A.N.; 2,4-Diaminothiazoles: A novel class of glycogen synthase kinase-3 (GSK-3) inhibitors. 11th RSC-SCI Med Chem Symp (Sept 9 2001, Cambridge) 2001, Abst P20. |
| 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) | 12034 | 4-Chlorophenylamine; 4-Chloroaniline; p-Chloroaniline | 106-47-8 | C6H6ClN | 详情 | 详情 |
| (II) | 22146 | 1-isothiocyanatobenzene; phenyl isothiocyanate | 103-72-0 | C7H5NS | 详情 | 详情 |
| (III) | 19648 | Cyanamide | 420-04-2 | CH2N2 | 详情 | 详情 |
| (IV) | 53541 | 1-[3-(benzyloxy)phenyl]-2-bromo-1-ethanone | n/a | C15H13BrO2 | 详情 | 详情 |
| (V) | 53545 | (Z)-3-({2-[3-(benzyloxy)phenyl]-2-oxoethyl}sulfanyl)-3-(4-chloroanilino)-2-propenenitrile | n/a | C24H19ClN2O2S | 详情 | 详情 |