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【结 构 式】 
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【药物名称】S-37435 【化学名称】N-[1(R)-[N-(3-Amino-2-hydroxypropyl)carbamoyl]-2-naphthylethyl]-4-(4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepin-5-yl)butyramide hydrochloride 【CA登记号】220977-91-3, 220979-20-4 ((R)-isomer, free base), 220979-21-5 ((S)-isomer, free base) 【 分 子 式 】C29H35ClN4O4S 【 分 子 量 】571.1437 |
【开发单位】Kaken (Originator), Molecular Research Institute (Originator) 【药理作用】ENDOCRINE DRUGS, Pituitary Disorder Therapy, Treatment of Growth Hormone Deficiency, Treatment of Growth Hormone Secretion Disorders, Growth Hormone Secretagogues |
合成路线1
The monoamine intermediate (IV) has been obtained as follows: The condensation of 2(R)-(benzyloxycarbonylamino)-3-(2-naphthyl)propionic acid (I) with 3-(tert-butoxycarbonylamino)-2-hydroxypropylamine (II) gives the corresponding amide (III), which is regioselectively deprotected by hydrogenolysis to yield the desired monoamine (IV). The condensation of 2,3,4,5-tetrahydro-1,5-benzothiazepin-4-one (V) with 4-chlorobutyric acid ethyl ester (VI) gives the corresponding cyclic amide (VII), which is hydrolyzed to afford the carboxylic acid (VIII). The condensation of acid (VIII) with the intermediate amine (IV) provides the amide (IX), which is finally N-deprotected to furnish the target diamide.
| 【1】 Huang, P.; Funamizu, H.; Loew, G.H.; et al.; Rational design, discovery, and synthesis of a novel series of potent growth hormone secretagogues. J Med Chem 2001, 44, 24, 4082. |
| 【2】 Salmon, R.; Sunley, R.L.; Godfrey, C.R.A.; Urch, C.J.; Lewis, T.; Bishop, N.D. (AstraZeneca plc); Bicycle amine derivs.. US 5912254; US 6066646 . |
| 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) | 54458 | (2R)-2-{[(benzyloxy)carbonyl]amino}-3-(2-naphthyl)propanoic acid | C21H19NO4 | 详情 | 详情 | |
| (II) | 54459 | tert-butyl 3-amino-2-hydroxypropylcarbamate | C8H18N2O3 | 详情 | 详情 | |
| (III) | 54460 | benzyl (1R)-2-({3-[(tert-butoxycarbonyl)amino]-2-hydroxypropyl}amino)-1-(2-naphthylmethyl)-2-oxoethylcarbamate | C29H35N3O6 | 详情 | 详情 | |
| (IV) | 54461 | tert-butyl 3-{[(2R)-2-amino-3-(2-naphthyl)propanoyl]amino}-2-hydroxypropylcarbamate | C21H29N3O4 | 详情 | 详情 | |
| (V) | 48910 | 2,3,4,5-Tetrahydro-1,5-benzothiazepin-4-one | C9H9NOS | 详情 | 详情 | |
| (VI) | 54462 | 4-Chlorobutyric acid ethyl ester; Ethyl 4-chlorobutyrate | 3153-36-4 | C6H11ClO2 | 详情 | 详情 |
| (VII) | 54463 | ethyl 4-[4-oxo-3,4-dihydro-1,5-benzothiazepin-5(2H)-yl]butanoate | C15H19NO3S | 详情 | 详情 | |
| (VIII) | 54464 | 4-[4-oxo-3,4-dihydro-1,5-benzothiazepin-5(2H)-yl]butanoic acid | C13H15NO3S | 详情 | 详情 | |
| (IX) | 54465 | tert-butyl 2-hydroxy-3-{[(2R)-3-(2-naphthyl)-2-({4-[4-oxo-3,4-dihydro-1,5-benzothiazepin-5(2H)-yl]butanoyl}amino)propanoyl]amino}propylcarbamate | C34H42N4O6S | 详情 | 详情 |