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【结 构 式】 
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【药物名称】NNC-57-0588 【化学名称】1-[4-Amino-2-(propylamino)thiazol-5-yl]-1-(3-pyridyl)methanone 【CA登记号】353512-12-6 【 分 子 式 】C12H14N4OS 【 分 子 量 】262.33558 |
【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-propylthiourea (I) with 2-bromo-1-(3-pyridyl)ethanone (II) in ethanol/acetone gives the N1-amidino-S-[2-oxo-2-(3-pyridyl)ethyl]-N3-propylisothiourea (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) | 53534 | 1-Amidino-3-propyl-2-thiourea | n/a | C5H12N4S | 详情 | 详情 |
| (II) | 53058 | (2-benzyl-4,8,8-trimethyl-6,10-dioxa-2-azaspiro[4.5]dec-4-yl)methyl azide; 4-(azidomethyl)-2-benzyl-4,8,8-trimethyl-6,10-dioxa-2-azaspiro[4.5]decane | n/a | C18H26N4O2 | 详情 | 详情 |
| (III) | 53535 | N-[(Z)-{[2-oxo-2-(3-pyridinyl)ethyl]sulfanyl}(propylamino)methylidene]guanidine | n/a | C12H17N5OS | 详情 | 详情 |
合成路线2
The reaction of propylamine (I) with di(2-pyridyl)thione (DPT) gives the corresponding isothiocyanate (II), which is condensed with cyanamide (III) and 2-bromo-1-(3-pyridyl)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) | 23923 | 1-propanamine | 107-10-8 | C3H9N | 详情 | 详情 |
| (II) | 53536 | Isothiocyanic acid n-propyl ester; n-Propyl isothiocyanate; Propyl isothiocyanate | 628-30-8 | C4H7NS | 详情 | 详情 |
| (III) | 19648 | Cyanamide | 420-04-2 | CH2N2 | 详情 | 详情 |
| (IV) | 53085 | 2-bromo-1-(3-pyridinyl)-1-ethanone | n/a | C7H6BrNO | 详情 | 详情 |
| (V) | 53537 | (Z)-3-{[2-oxo-2-(3-pyridinyl)ethyl]sulfanyl}-3-(propylamino)-2-propenenitrile | n/a | C13H15N3OS | 详情 | 详情 |