- Pyrazolobenzodiazepines: Part I. Synthesis and SAR of a potent class of kinase inhibitors
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A novel series of pyrazolobenzodiazepines 3 has been identified as potent inhibitors of cyclin-dependent kinase 2 (CDK2). Their synthesis and structure-activity relationships (SAR) are described. Representative compounds from this class reversibly inhibit CDK2 activity in vitro, and block cell cycle progression in human tumor cell lines. Further exploration has revealed that this class of compounds inhibits several kinases that play critical roles in cancer cell growth and division as well as tumor angiogenesis. Together, these properties suggest a compelling basis for their use as antitumor agents.
- Liu, Jin-Jun,Daniewski, Irena,Ding, Qingjie,Higgins, Brian,Ju, Grace,Kolinsky, Kenneth,Konzelmann, Fred,Lukacs, Christine,Pizzolato, Giacomo,Rossman, Pamela,Swain, Amy,Thakkar, Kshitij,Wei, Chung-Chen,Miklowski, Dorota,Yang, Hong,Yin, Xuefeng,Wovkulich, Peter M.
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scheme or table
p. 5984 - 5987
(2010/10/21)
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- Reactions of 1,4-benzodiazepinic N-nitrosoamidines with tosylmethyl isocyanide: A novel synthesis of midazolam
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Reaction of 1,4-benzodiazepinic N-nitrosoamidines, used as synthetic equivalents of imidoyl chlorides, with the monoanion of tosylmethyl isocyanide is described. The process gives entry to 3-(4-tosyl)imidazo[1,5-a][1,4] benzodiazepines, compounds which have not been described yet in the literature. These systems can be derivatized to the corresponding trisubstituted 1,4-benzodiazepines by alkylation or acylation of the imidazole ring. These new heterocyclic derivatives are potentially useful in the field of medicinal chemistry. In addition, midazolam 3, the anesthetic properties of which are well established, can be easily prepared in one step by desulfonylation of compound 7a.
- Del Pozo, Carlos,Macias, Alberto,Alonso, Eduardo,Gonzalez, Javier
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p. 2697 - 2703
(2007/10/03)
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- Synthesis and spectral properties of 2-[(o- and p-substituted)aminophenyl]-3H-5-[(o- and p-substituted)phenyl]-7-chloro-1,4-benzodiazepines
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A series of twelve new 2-[(o- and p-substituted)aminophenyl]-3H-5-[(o- and p-substituted)phenyl]-7-chloro-1,4-benzodiazepines, which have possible pharmacological properties has been obtained. The synthesis was carried out following six steps. The structure of all products was corroborated by ir, 1H nmr, 13C nmr and ms. In addition for the compound 2-(o-chloroaminophenyl)-3H-5-(o-fluorophenyl)-7-chloro-1,4-benzodiazepine 7, its structure was confirmed by X-ray diffraction.
- Cortes Cortes,Salazar Franco,Garcia Mellado
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p. 663 - 669
(2007/10/03)
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- 2-(2-Alkynylamino)-3H-1,4-benzodiazepines
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Novel 6-substituted 4H-imidazo[1,2-a][1,4]benzodiazepines, the intermediate 5-substituted-2-(2-alkynylamino)-3H-1,4-benzodiazepines, pharmacologically acceptable acid addition salts thereof, and processes for their production. The compounds of this invention and the pharmacologically acceptable acid addition salts thereof are central nervous system depressants. They are useful as sedatives, hypnotics, tranquilizers, muscle relaxants and anticonvulsants, and also as feed additives for increasing growth rate and feed efficiency of livestock and poultry, milk production in the mammalian species and egg production in avian species.
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