Ti(III)-Mediated reductions of N-hydroxy imidazoles to 1-protio-2,4(5)-disubstituted derivatives

Lipshutz, Bruce H.; Morey, Matthew C.

doi:10.1016/s0040-4039(01)80146-5

Cited by 18 publications

(6 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both isomers participated in the key cyclization reaction when treated with CBZ piperidine-4-carboxaldehyde and ammonium acetate in acetic acid at reflux, to afford the hydroxyimidazole 27 . Several methods are available for the reduction of hydroxyimidazoles, including P(OMe) 3 , Raney nickel-catalyzed hydrogenation, and aqueous titanium trichloride . Hydrogenation would be incompatible with the CBZ functionality and further complicated by the presence of the (methylthio)pyrimidine.…”

Section: Chemistrymentioning

confidence: 99%

Design and Synthesis of Potent, Selective, and Orally Bioavailable Tetrasubstituted Imidazole Inhibitors of p38 Mitogen-Activated Protein Kinase

et al. 1999

View full text Add to dashboard Cite

Novel potent and selective diarylimidazole inhibitors of p38 MAP (mitogen-activated protein) kinase are described which have activity in both cell-based assays of tumor necrosis factor-alpha (TNF-alpha) release and an animal model of rheumatoid arthritis. The SAR leading to the development of selectivity against c-Raf and JNK2alpha1 kinases is presented, with key features being substitution of the 4-aryl ring with m-trifluoromethyl and substitution of the 5-heteroaryl ring with a 2-amino substituent. Cell-based activity was significantly enhanced by incorporation of a 4-piperidinyl moiety at the 2-position of the imidazole which also enhanced aqueous solubility. In general, oral bioavailability of this class of compounds was found to be poor unless the imidazole was methylated on nitrogen. This work led to identification of 48, a potent (p38 MAP kinase inhibition IC50 0.24 nM) and selective p38 MAP kinase inhibitor which inhibits lipopolysaccharide-stimulated release of TNF-alpha from human blood with an IC50 2.2 nM, shows good oral bioavailability in rat and rhesus monkey, and demonstrates significant improvement in measures of disease progression in a rat adjuvant-induced arthritis model.

show abstract

Section: Chemistrymentioning

confidence: 99%

Design and Synthesis of Potent, Selective, and Orally Bioavailable Tetrasubstituted Imidazole Inhibitors of p38 Mitogen-Activated Protein Kinase

et al. 1999

View full text Add to dashboard Cite

show abstract

“…Several methods have been devised for the reductive removal of the N -hydroxy group of 1-hydroxyimidazoles. Such dehydroxylation has been effected by palladium-catalyzed hydrogenolysis at room temperature for extended reaction times , or by using titanium trichloride, sodium borohydride, sodium bis(2-methoxyethoxy) aluminum dihydride (Red-Al, Aldrich), or zinc in formic acid . Therefore, the present method for introduction of substituents in 1-hydroxyimidazole also provides access to the corresponding substituted imidazoles.…”

Section: Resultsmentioning

confidence: 99%

“…They are usually obtained by condensation of monooximes of 1,2-diketones with ammonia and an aldehyde − or with an aldimine or by reaction of olefins and nitrosyl hydrogen sulfate in the presence of aliphatic nitriles. − 1-Hydroxyimidazoles have been obtained by selective reduction of 3-hydroxyimidazole 1-oxide. , prepared by cyclization of a 1,2-diketone, an aldehyde, and hydroxylamine. Finally, 1-hydroxyimidazole ( 5a ) was synthesized by N-oxidation of imidazole with peroxyphthalic acid or 3-chloroperbenzoic acid …”

Section: Introductionmentioning

confidence: 99%

Synthesis of 2-Substituted 1-Hydroxyimidazoles through Directed Lithiation

et al. 1998

View full text Add to dashboard Cite

Benzylation of 3-hydroxyimidazole 1-oxide gave 3-(benzyloxy)imidazole 1-oxide, which was deoxygenated with phosphorous trichloride to produce 1-(benzyloxy)imidazole. 1-(Benzyloxy)imidazole was deprotonated selectively at C-2 by n-butyllithium. The anion formed was reacted with electrophiles to give 1-(benzyloxy)imidazoles with carbon, halogen, silicon, or sulfur substituents at the 2-position. Subsequent debenzylation afforded 2-substituted 1-hydroxyimidazoles which in turn could be deoxygenated to give 2-substituted imidazoles.

show abstract

“…The substitution of the nitrogen of the imidazole heterocycle is also detrimental to activity (6,36,37,Table 4).…”

Section: -Fluoroimidazole Chemistrymentioning

confidence: 99%

Synthesis and structure-activity relationships of new cephalosporins with aminoimidazoles at C-7. Effect of the pKa of the C-7 aminoimidazole on antibacterial spectrum and .BETA.-lactamase stability.

Jung¹,

Boucherot²,

Delvare³

et al. 1993

J. Antibiot.

View full text Add to dashboard Cite

Ti(III)-Mediated reductions of N-hydroxy imidazoles to 1-protio-2,4(5)-disubstituted derivatives

Cited by 18 publications

References 5 publications

Design and Synthesis of Potent, Selective, and Orally Bioavailable Tetrasubstituted Imidazole Inhibitors of p38 Mitogen-Activated Protein Kinase

Design and Synthesis of Potent, Selective, and Orally Bioavailable Tetrasubstituted Imidazole Inhibitors of p38 Mitogen-Activated Protein Kinase

Synthesis of 2-Substituted 1-Hydroxyimidazoles through Directed Lithiation

Synthesis and structure-activity relationships of new cephalosporins with aminoimidazoles at C-7. Effect of the pKa of the C-7 aminoimidazole on antibacterial spectrum and .BETA.-lactamase stability.

Contact Info

Product

Resources

About