BPDZ-44-药物合成数据库

【药物名称】BPDZ-44

化学结构式(Chemical Structure):

参考文献No.	546832
标题:	Preparation and pharmacological evaluation of the R- and S-enantiomers of 3-(2'-butylamino)-4H- and 3-(3'-methyl-2'-butylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxide, two tissue selective ATP-sensitive potassium channel openers
作者:	Khelili, S.; de Tullio, P.; Lebrun, P.; Fillet, M.; Antoine, M.H.; Ouedraogo, R.; Dupont, L.; Fontaine, J.; Felekidis, A.; Leclerc, G.; Delarge, J.; Pirotte, B.
来源:	Bioorg Med Chem 1999,7(8),1513

合成路线图解说明: The synthesis of the intermediates, the chiral amines (R)(-)-1,2-dimethylpropylamine (R)(-)-(I) and (S)(+)-1,2-dimethylpropylamine (S)(+)-(I) has been performed as follows: (R)(-)-1,2-Dimethylpropylamine (R)(-)-(I): The reaction of racemic 1,2-dimethylpropylamine (rac)(I) with 2(S)-(6-methoxynaphthalen-2-yl)propionic acid (S)(+)-(II) (S-naproxen) in ethanol gives the ammonium salt (III) as a diastereomeric mixture from which the (R,S)-diastereomer is obtained by successive crystallizations. Finally, this diastereomer is treated with NaOH in water to obtain the target (R)(-)-amine (R)(-)-(I). (S)(+)-1,2-Dimethylpropylamine (S)(+)-(I): The reaction of racemic 1,2-dimethylpropylamine (rac)-(I) with 2(S)-hydroxy-2-phenylacetic acid (S)(+)-(IV) (S-mandelic acid) in ethanol gives the ammonium salt (V) as a diastereomeric mixture from which the (S,S)-diastereomer is obtained by successive crystallizations. Finally, this diastereomer is treated with NaOH in water to obtain the target (S)(+)-amine (S)(+)-(I).

合成路线图解说明: The reaction of 4-hydroxypyridine-3-sulfonic acid (VI) with POCl3 and PCl5 gives 4-chloropyridine-3-sulfonyl chloride (VII), which is treated with ammonia at room temperature yielding the sulfonamide (VIII). The resulting sulfonamide (VIII) was heated with ammonia to afford 4-aminopyridine-3-sulfonamide (IX), which is cyclized with urea (X) to provide the pyridothiadiazinone (XI). The reaction of (XI) with P2S5 in pyridine gives the corresponding thione (XII), which is methylated with methyl iodide to furnish the methylsulfanyl compound (XIII). Finally, this compound (XIII) is condensed with the chiral intermediate (R)(-)-1,2-dimethylpropylamine (R)(-)-(I) to afford the chiral (R)(-)-target compound. The condensation of the intermediate methylsulfanyl compound (XIII) with the chiral intermediate (S)(+)-1,2-dimethylpropylamine (S)(+)-(I) to afford the chiral (S)(+)-target compound.

合成路线图解说明: The reaction of 4-hydroxypyridine-3-sulfonic acid (I) with POCl3 and PCl5 gives 4-chloropyridine-3-sulfonyl chloride (II), which is treated with ammonia at room temperature yielding the sulfonamide (III). The resulting sulfonamide (VIII) was heated with ammonia to afford 4-aminopyridine-3-sulfonamide (IV), which is cyclized with urea (V) to provide the pyridothiadiazinone (VI). The reaction of (XI) with P2S5 in pyridine gives the corresponding thione (VII), which is methylated with methyl iodide to furnish the methylsulfanyl compound (VII) (2). Finally, this compound (VIII) is condensed with the chiral intermediate (R)(-)-1-methylpropylamine (R)(-)-(IX) to afford the chiral (R)(-)-target compound. The condensation of the intermediate methylsulfanyl compound (VIII) with the chiral intermediate (S)(+)-1-methylpropylamine (S)(+)-(IX) to afford the chiral (S)(+)-target compound.

参考文献No.	608338
标题:	3-(Alkylamino)-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides as powerful inhibitors of insulin release from rat oancreatic B-cells: a new class of potassium channel openers?
作者:	Pirotte, B.; De Tullio, P.; Lebrun, P.; Antoine, M.H.; Fontaine, J.; Masereel, B.; Schynts, M.; Dupont, L.; Herchuelz, A.; Delarge, J.
来源:	J Med Chem 1993,36(21),3211-13

合成路线图解说明: The reaction of 4-hydroxypyridine-3-sulfonic acid (VI) with POCl3 and PCl5 gives 4-chloropyridine-3-sulfonyl chloride (VII), which is treated with ammonia at room temperature yielding the sulfonamide (VIII). The resulting sulfonamide (VIII) was heated with ammonia to afford 4-aminopyridine-3-sulfonamide (IX), which is cyclized with urea (X) to provide the pyridothiadiazinone (XI). The reaction of (XI) with P2S5 in pyridine gives the corresponding thione (XII), which is methylated with methyl iodide to furnish the methylsulfanyl compound (XIII). Finally, this compound (XIII) is condensed with the chiral intermediate (R)(-)-1,2-dimethylpropylamine (R)(-)-(I) to afford the chiral (R)(-)-target compound. The condensation of the intermediate methylsulfanyl compound (XIII) with the chiral intermediate (S)(+)-1,2-dimethylpropylamine (S)(+)-(I) to afford the chiral (S)(+)-target compound.

合成路线图解说明: The reaction of 4-hydroxypyridine-3-sulfonic acid (I) with POCl3 and PCl5 gives 4-chloropyridine-3-sulfonyl chloride (II), which is treated with ammonia at room temperature yielding the sulfonamide (III). The resulting sulfonamide (VIII) was heated with ammonia to afford 4-aminopyridine-3-sulfonamide (IV), which is cyclized with urea (V) to provide the pyridothiadiazinone (VI). The reaction of (XI) with P2S5 in pyridine gives the corresponding thione (VII), which is methylated with methyl iodide to furnish the methylsulfanyl compound (VII) (2). Finally, this compound (VIII) is condensed with the chiral intermediate (R)(-)-1-methylpropylamine (R)(-)-(IX) to afford the chiral (R)(-)-target compound. The condensation of the intermediate methylsulfanyl compound (VIII) with the chiral intermediate (S)(+)-1-methylpropylamine (S)(+)-(IX) to afford the chiral (S)(+)-target compound.