273. Derivatives of 6-aminopenicillanic acid. Part II. Trisubstituted acetyl derivatives

Brain, E. G.; Doyle, Frank; Hardy, Kenneth D.; Long, A. A. W.; Mehta, M. D.; Miller, David D.; Nayler, J. H. C.; Soulal, M. J.; Stove, E. R.; Thomas, George

doi:10.1039/jr9620001445

Cited by 15 publications

(8 citation statements)

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“…quality and freshly distilled before use. [26] Tris (27): Under N 2 atmosphere and ice cooling, 26 (1.87 g, 5.00 mmol) was dissolved in abs. As petroleum ether (PE) the fraction 40-80 8C was used.…”

Section: Methodsmentioning

confidence: 99%

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Development of an (S)‐1‐{2‐[Tris(4‐methoxyphenyl)methoxy]ethyl}piperidine‐3‐carboxylic acid [(S)‐SNAP‐5114] Carba Analogue Inhibitor for Murine γ‐Aminobutyric Acid Transporter Type 4

Pabel

Faust²,

Prehn

et al. 2012

ChemMedChem

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A series of GABA uptake inhibitors related to (S)-1-{2-[tris(4-methoxyphenyl)methoxy]ethyl}piperidine-3-carboxylic acid [(S)-SNAP-5114], the most potent mGAT4 inhibitor known so far, were synthesized and biologically evaluated for their inhibitory potency at the four GABA uptake transporters mGAT1-4 stably expressed in HEK-293 cell lines. New analogues were developed with potencies that are similar to or slightly higher than those of current mGAT4 inhibitors, but with distinctly improved chemical stability. (S)-Nipecotic acid derivatives possessing a 2-[1-(4-methoxy-2-methylphenyl)-1,1-bis(4-methoxyphenyl)methoxy]ethyl (DDPM-859) or a 4,4,4-tris(4-methoxyphenyl)but-2-en-1-yl moiety (DDPM-1457) were found to exhibit pIC(50) values of 5.78 and 5.87, respectively. Thus, as mGAT4 inhibitors, these compounds compare well with (S)-SNAP-5114 (pIC(50) =5.71), but are far more stable than the latter. Moreover, DDPM-859 displays a more favorable subtype selectivity for mGAT4 versus mGAT3 than does (S)-SNAP-5114.

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Section: Methodsmentioning

confidence: 99%

“…Then, a solution of 20[27] (2.3 g, 6.2 mmol) in THF (20 mL) was added dropwise. calcd for C methoxyphenyl)ethanol(21): Under argon atmosphere, LiAlH 4 (0.56 g, 15 mmol) was suspended in THF (20 mL) and cooled to 0 8C.…”

mentioning

confidence: 99%

Development of an (S)‐1‐{2‐[Tris(4‐methoxyphenyl)methoxy]ethyl}piperidine‐3‐carboxylic acid [(S)‐SNAP‐5114] Carba Analogue Inhibitor for Murine γ‐Aminobutyric Acid Transporter Type 4

Pabel

Faust²,

Prehn

et al. 2012

ChemMedChem

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“…G ourevitch et al [13, 14 15] were the first to discover that the steric effect of phenoxyisobutylpenicillin was responsible for its staphylococcal ^-lactamase-resistant nature. Semisynthetic penicillins such as triphenylmethylpenicillin [4], methicillin [10], 3:5-disubstituted-4-isoxazolyl penicillins (oxacillin, clox acillin, dicloxacillin) [9,11,26,31], ancillin [14], nafcillin [24] and quin acillin [32] are also /5-lactamase-resistant. These penicillins all have side chains which introduce a steric effect that could cause resistance by inter fering with the effective attachment of the penicillin molecule to the ac tive sites on the enzyme [21].…”

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confidence: 99%

Kinetics of <i>β</i>–Lactamase Inactivation of Penicillins

Hou¹,

Poole²

1973

Chemotherapy

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Experiments were conducted that showed Staphylococcusaureusβ-lactamase activity to be inhibited the most by dicloxacillin, cephaloglycin, and 7-ACA, to a lesser degree by cloxacillin, quinacillin, oxacillin, 6-APA, cephalexin, nafcillin, and ancillin and least of all by methicillin. Bacillus cereus β-lactamase activity was inhibited most by nafcillin and dicloxicillin and only moderately by all the other inhibitors cited, including methicillin, which was least effective. The degree of inhibition was shown to depend on the structural characteristics of the inhibitor, the time of exposure of enzyme to inhibitor, and the ratio of amount of inhibitor to amount of substrate. The inhibition was of the competitive type. The compounds having the highest affinity for the enzyme or the lowest K_i value were the strongest inhibitors and were most effective in protecting the susceptible substrate from hydrolysis.

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“…The effect of simply increasing the level of substitution on methylpenicillin is illustrated at the top of Tables 3 and 4. Resistance to staphylococcal penicillinase becomes effective only when the a-carbon is completely substituted by groupings of sufficient bulk (BRAIN et al 1962;DOYLE and NAYLER 1966). Bulk at the p-carbon is ineffective.…”

Section: Ll Penicillinase-resistant Penicillinsmentioning

confidence: 98%

“…Phenyl penicil-lins and equivalent heterocyclic analogs have marked stability to penicillinase when both ortho positions are occupied by any of a large variety of substituents (DOYLE et al 1962 a;BRAIN et al 1963). In fact with a six-membered ring (or a fused ring system of equivalent or greater bulk, e.g., quinacillin) a single ortho substituent of proper type can be sufficient for good penicillinase resistance.…”

Section: Ll Penicillinase-resistant Penicillinsmentioning

confidence: 99%

β-Lactam Antibiotics: Structure-Activity Relationships

Hoover¹

1983

Antibiotics

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273. Derivatives of 6-aminopenicillanic acid. Part II. Trisubstituted acetyl derivatives

Cited by 15 publications

References 0 publications

Development of an (S)‐1‐{2‐[Tris(4‐methoxyphenyl)methoxy]ethyl}piperidine‐3‐carboxylic acid [(S)‐SNAP‐5114] Carba Analogue Inhibitor for Murine γ‐Aminobutyric Acid Transporter Type 4

Development of an (S)‐1‐{2‐[Tris(4‐methoxyphenyl)methoxy]ethyl}piperidine‐3‐carboxylic acid [(S)‐SNAP‐5114] Carba Analogue Inhibitor for Murine γ‐Aminobutyric Acid Transporter Type 4

Kinetics of <i>β</i>–Lactamase Inactivation of Penicillins

β-Lactam Antibiotics: Structure-Activity Relationships

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