【药物名称】
Tomoxiprole, MDL-035
【化学名】
3-Isopropyl-2-(4-methoxyphenyl)-3H-naphth[1,2-d]imidazole
【CAS登记号】
76145-76-1
【结构式】
【分子式】
C21-H20-N2-O
【分子量】
316.402
【原研厂家】
Lepetit (Originator)
【作用类别】
ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, Non-Steroidal Antiinflammatory Drugs
【研发状态】
Preclinical
【合成情况】
〖来源〗
Drugs Fut
〖合成路线〗
〖标题〗
Tomoxiprole
〖合成方法〗
Reaction of 1-nitroso-2-naphthol (I) with isopropylamine in water gives 2-isopropylamino-1-nitrosonaphthalene (II). After hydrogenation, condensation of the resulting 2-isopropylamino-1,2-naphthalendiamine (III) with p-methoxybenzaldehyde yields the 1,2-dihydro derivative (IV), which is converted to MDL-035 with palladium on carbon. Toluene is used as a solvent throughout the synthesis. The overall yield on a 20-kg scale is 57%.
〖作者〗
Casta馿r, J.; Chu, S.S.; Serradell, M.N.
〖参考〗
Casta馿r, J.; Chu, S.S.; Serradell, M.N.; Tomoxiprole. Drugs Fut 1985, 10, 2, 133
〖出处〗
Drugs Fut1985,10,(2):133
〖备注〗
Synthesis of 090565:
Reaction of 1-nitroso-2-naphthol (I) with isopropylamine in water gives 2-isopropylamino-1-nitrosonaphthalene (II). After hydrogenation, condensation of the resulting 2-isopropylamino-1,2-naphthalendiamine (III) with p-methoxy benzaldehyde yields the 1,2-dihydro derivative (IV), which is converted to MDL-035 with palladium on carbon. Toluene is used as a solvent throughout the synthesis. The overall yield on a 20-kg scale is 57% (1,2). (Scheme 09056501a)
Description
White, odorless, tasteless crystalline powder, m.p. 160-1? practically insoluble in pure water and alkaline aqueous solutions, but slightly soluble in simulated gastric juice (pH<2). All pharmacological and toxicological tests were done with the micronized form. Particle size distribution <20 microm., 90% in volume.
Manufacturer
Gruppo Lepetit SpA, Milan (Italy)
References
1. Toja, E., Selva, D. and Schiatti, P.; 3-Alkyl-2-aryl-3H-naphth[1,2-d]imidazoles, a novel class of nonacidic antiinflamatory agents.; J Med Chem 1984, 27; 610-616
2. Toja, E., Omodei-Sal? A. and Selva, D. (Grupo Lepetit SpA); EP 12.866, JP 80.92.376, US 4.340.607, US 4.435.417
〖来源〗
J Med Chem
〖合成路线〗
〖标题〗
3-Alkyl-2-ary?3H-naphth[1,2-d]imidazoles, a novel class of nonacidic antiinflammatory agents
〖合成方法〗
Reaction of 1-nitroso-2-naphthol (I) with isopropylamine in water gives 2-isopropylamino-1-nitrosonaphthalene (II). After hydrogenation, condensation of the resulting 2-isopropylamino-1,2-naphthalendiamine (III) with p-methoxybenzaldehyde yields the 1,2-dihydro derivative (IV), which is converted to MDL-035 with palladium on carbon. Toluene is used as a solvent throughout the synthesis. The overall yield on a 20-kg scale is 57%.
〖作者〗
Toja, E.; Schiatti, P.; Selva, D.
〖参考〗
Toja, E.; Schiatti, P.; Selva, D.; 3-Alkyl-2-ary?3H-naphth[1,2-d]imidazoles, a novel class of nonacidic antiinflammatory agents. J Med Chem 1984, 27, 5, 610-616
〖出处〗
J Med Chem1984,27,(5):610-616
〖备注〗
Synthesis of 090565:
Reaction of 1-nitroso-2-naphthol (I) with isopropylamine in water gives 2-isopropylamino-1-nitrosonaphthalene (II). After hydrogenation, condensation of the resulting 2-isopropylamino-1,2-naphthalendiamine (III) with p-methoxy benzaldehyde yields the 1,2-dihydro derivative (IV), which is converted to MDL-035 with palladium on carbon. Toluene is used as a solvent throughout the synthesis. The overall yield on a 20-kg scale is 57%. (Scheme 09056501a)
Description
White, odorless, tasteless crystalline powder, m.p. 160-1? practically insoluble in pure water and alkaline aqueous solutions, but slightly soluble in simulated gastric juice (pH<2). All pharmacological and toxicological tests were done with the micronized form. Particle size distribution <20 microm., 90% in volume.
〖来源〗
EP 0012866; JP 8092376; US 4340607; US 4435417
〖合成路线〗
〖标题〗
Antimicrobial 3H-naphto[1,2-d]imidazoles
〖合成方法〗
Reaction of 1-nitroso-2-naphthol (I) with isopropylamine in water gives 2-isopropylamino-1-nitrosonaphthalene (II). After hydrogenation, condensation of the resulting 2-isopropylamino-1,2-naphthalendiamine (III) with p-methoxybenzaldehyde yields the 1,2-dihydro derivative (IV), which is converted to MDL-035 with palladium on carbon. Toluene is used as a solvent throughout the synthesis. The overall yield on a 20-kg scale is 57%.
〖作者〗
Toja, E.; Omodei-Sale, A.; Selva, D. (Lepetit SpA)
〖参考〗
Toja, E.; Omodei-Sale, A.; Selva, D. (Lepetit SpA); Antimicrobial 3H-naphto[1,2-d]imidazoles. EP 0012866; JP 8092376; US 4340607; US 4435417
〖出处〗
EP 0012866; JP 8092376; US 4340607; US 4435417,,():
〖备注〗
Synthesis of 090565:
Reaction of 1-nitroso-2-naphthol (I) with isopropylamine in water gives 2-isopropylamino-1-nitrosonaphthalene (II). After hydrogenation, condensation of the resulting 2-isopropylamino-1,2-naphthalendiamine (III) with p-methoxy benzaldehyde yields the 1,2-dihydro derivative (IV), which is converted to MDL-035 with palladium on carbon. Toluene is used as a solvent throughout the synthesis. The overall yield on a 20-kg scale is 57%. (Scheme 09056501a)
Description
White, odorless, tasteless crystalline powder, m.p. 160-1? practically insoluble in pure water and alkaline aqueous solutions, but slightly soluble in simulated gastric juice (pH<2). All pharmacological and toxicological tests were done with the micronized form. Particle size distribution <20 microm., 90% in volume.
