The organometallic route to benzylamine type monoamine oxidase inhibitors

Schlosser, Manfred; Geneste, Hervé

doi:10.1016/s0040-4020(98)00602-4

Cited by 5 publications

(5 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The best protective group is the one that can be omitted . The directed ortho- metalation of unprotected benzoic acids can be achieved by treatment with 2.2 equiv of s -BuLi/TMEDA in THF at −90 °C; , the resulting dilithiated species easily react with a variety of electrophiles to give the ortho- substituted products.…”

mentioning

confidence: 99%

“…The best protective group is the one that can be omitted. 2 The directed ortho-metalation of unprotected benzoic acids can be achieved by treatment with 2.2 equiv of s-BuLi/TMEDA in THF at -90 °C; 3,4 the resulting dilithiated species easily react with a variety of electrophiles to give the ortho-substituted products. Alternatively, 2,3-disubstituted benzoic acids are readily available by lithiating 1,2-disubstituted compounds, metalation occurring to the more effective directing group-neighboring position.…”

mentioning

confidence: 99%

“…We have embarked on a detailed investigation of the deprotonations of 3-chlorobenzoic acid (1) and 3-bromobenzoic acid (2), varying the base, metalation temperature, and exposure times (Table 1). Lithium diisopropylamide (LDA) is not suitable for the generation of lithium 2-lithio-3-chloro and 2-lithio-3-bromobenzoates (2Li-1 and 2Li-2, respectively): deuteriation (deuterium oxide quench) at the position flanked by both substituents does not exceed 42% (entries 1-3, 8, and 9).…”

mentioning

confidence: 99%

See 2 more Smart Citations

ortho-Metalation of Unprotected 3-Bromo and 3-Chlorobenzoic Acids with Hindered Lithium Dialkylamides

Gohier

Mortier

2003

J. Org. Chem.

View full text Add to dashboard Cite

Upon treatment of 3-chloro/bromobenzoic acids with hindered lithium dialkylamides (LDA or LTMP) at -50 degrees C, lithium 3-chloro/bromo-2-lithiobenzoates are generated. These dianions can be trapped as such to afford after electrophilic quenching a variety of simple 2-substituted-3-chloro/bromobenzoic acids. The 3-bromo-2-lithiobenzoate is less stable than the corresponding 3-chloro derivative and partly eliminates lithium bromide, thus setting free lithium 2,3- and 3,4-dehydrobenzoates that can be intercepted in situ with the hindered base.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

ortho-Metalation of Unprotected 3-Bromo and 3-Chlorobenzoic Acids with Hindered Lithium Dialkylamides

Gohier

Mortier

2003

J. Org. Chem.

View full text Add to dashboard Cite

show abstract

“…Treatment of 62 with n-butyllithium followed by dimethyl disulfide gave thioanisole 63 in excellent yield. 46 Treatment with N-chlorosuccinimide followed by Michaelis-Arbuzov reaction with triethyl phosphite generated phosphonate 64. 47 Deprotection with tetrabutylammonium fluoride afforded phenol 65.…”

Section: Chemistrymentioning

confidence: 99%

“…An analogue with a sulfur-connected side chain was also prepared as outlined in Scheme . Treatment of 62 with n -butyllithium followed by dimethyl disulfide gave thioanisole 63 in excellent yield . Treatment with N -chlorosuccinimide followed by Michaelis−Arbuzov reaction with triethyl phosphite generated phosphonate 64 .…”

Section: Chemistrymentioning

confidence: 99%

Synthesis and Biological Evaluation of a Series of Liver-Selective Phosphonic Acid Thyroid Hormone Receptor Agonists and Their Prodrugs

et al. 2008

View full text Add to dashboard Cite

Phosphonic acid (PA) thyroid hormone receptor (TR) agonists were synthesized to exploit the poor distribution of PA-based drugs to extrahepatic tissues and thereby to improve the therapeutic index. Nine PAs showed excellent TR binding affinities (TRbeta(1), K(i) < 10 nM), and most of them demonstrated significant cholesterol lowering effects in a cholesterol-fed rat (CFR) model. Unlike the corresponding carboxylic acid analogue and T(3), PA 22c demonstrated liver-selective effects by inducing maximal mitochondrial glycerol-3-phosphate dehydrogenase activity in rat liver while having no effect in the heart. Because of the low oral bioavailability of PA 22c, a series of prodrugs was synthesized and screened for oral efficacy in the CFR assay. The liver-activated cyclic 1-(3-chlorophenyl)-1,3-propanyl prodrug (MB07811) showed potent lipid lowering activity in the CFR (ED(50) 0.4 mg/kg, po) and good oral bioavailability (40%, rat) and was selected for development for the treatment of hypercholesterolemia.

show abstract

Original preparation of conjugates for antibody production against Amicoumacin-related anti-microbial agents

Shinkaruk

Bennetau

Babin

et al. 2008

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

The organometallic route to benzylamine type monoamine oxidase inhibitors

Cited by 5 publications

References 9 publications

ortho-Metalation of Unprotected 3-Bromo and 3-Chlorobenzoic Acids with Hindered Lithium Dialkylamides

ortho-Metalation of Unprotected 3-Bromo and 3-Chlorobenzoic Acids with Hindered Lithium Dialkylamides

Synthesis and Biological Evaluation of a Series of Liver-Selective Phosphonic Acid Thyroid Hormone Receptor Agonists and Their Prodrugs

Original preparation of conjugates for antibody production against Amicoumacin-related anti-microbial agents

Contact Info

Product

Resources

About