26831-48-1Relevant articles and documents
Structure-Anti-Parkinson Activity Relationships in the Aminoadamantanes. Influence of Bridgehead Substitution
Henkel, James G.,Hane, Jeffrey T.,Gianutsos, Gerald
, p. 51 - 56 (1982)
A limited series of bridgehead alkyl-, dialkyl- and trialkyl-substituted amantadines was synthesized and tested for potential anti-Parkinson activity as dopamine (DA) agonists.The compounds were evaluated using a battery of three murine bioassays, including stimulation of locomotor activity, induction of circling in animals with unilateral striatal lesions, and reversal of reserpine/α-methyltyrosine induced akinesia.Apparent mechanistic differences were seen between the methyl-substituted series and the ethyl-substituted series.While activities in both series increase with increasing liphophilicity, the methyl series (1b-d), as well as amantadine itself (1a) exhibits only indirect DA agonist activity, as evidenced by ipsilateral rotation in the circling model and no significant difference from control in reversal of akinesia.The ethyl series (1e,f) exhibits weak but reprodicible direct DA agonist activity, as shown by contralateral rotation in the circling assay for 1e and reversal of akinesia by 1e and 1f.The 3-n-propyl derivative (1g) was devoid of any DA agonist activity.
Synthesis and Structure-Activity Relationships of Ring-Opened Bengamide Analogues against Methicillin-Resistant Staphylococcus aureus?
Yu, Chen-Xi,Wei, Bing-Yan,Kong, Xue-Qing,Yang, Cai-Guang,Nan, Fa-Jun
supporting information, p. 671 - 676 (2021/02/12)
Methicillin-resistant Staphylococcus aureus (MRSA) has become a major threat on public health because of the increase of clinically isolated strains that exhibit resistance to many antibiotics. Therefore, development of new antibiotics for the treatment of MRSA infection is a sustained challenge. We have previously identified a ring-opened bengamide analogue L472-2 that displays moderate activity against the growth of S. aureus. In our previous work, we started from L472-2 and identified a class of analogues containing alkynyl groups which have the potential to activate SaClpP activity but moderate antibacterial activity. Herein, we focused on the antibacterial activity of L472-2, and a novel series of ring-opened bengamide analogues were synthesized and their activities were evaluated against MRSA. By conducting a compact analysis of the structure-activity relationships (SAR) of these analogues, we found that an adamantane ethanol ester bengamide 2j showed excellent antibacterial activity towards six S. aureus strains, including MRSA, while it does not activate ClpP. Therefore, these bengamide analogues represent a new class of candidates that suppress MRSA viability.
Controlling Plasma Stability of Hydroxamic Acids: A MedChem Toolbox
Hermant, Paul,Bosc, Damien,Piveteau, Catherine,Gealageas, Ronan,Lam, Baovy,Ronco, Cyril,Roignant, Matthieu,Tolojanahary, Hasina,Jean, Ludovic,Renard, Pierre-Yves,Lemdani, Mohamed,Bourotte, Marilyne,Herledan, Adrien,Bedart, Corentin,Biela, Alexandre,Leroux, Florence,Deprez, Benoit,Deprez-Poulain, Rebecca
, p. 9067 - 9089 (2017/11/14)
Hydroxamic acids are outstanding zinc chelating groups that can be used to design potent and selective metalloenzyme inhibitors in various therapeutic areas. Some hydroxamic acids display a high plasma clearance resulting in poor in vivo activity, though they may be very potent compounds in vitro. We designed a 57-member library of hydroxamic acids to explore the structure-plasma stability relationships in these series and to identify which enzyme(s) and which pharmacophores are critical for plasma stability. Arylesterases and carboxylesterases were identified as the main metabolic enzymes for hydroxamic acids. Finally, we suggest structural features to be introduced or removed to improve stability. This work thus provides the first medicinal chemistry toolbox (experimental procedures and structural guidance) to assess and control the plasma stability of hydroxamic acids and realize their full potential as in vivo pharmacological probes and therapeutic agents. This study is particularly relevant to preclinical development as it allows obtaining compounds equally stable in human and rodent models.
