4596-53-6Relevant articles and documents
Synthesis of Carbapenems Containing Peptidoglycan Mimetics and Inhibition of the Cross-Linking Activity of a Transpeptidase of l,d Specificity
Saidjalolov, Saidbakhrom,Edoo, Zainab,Fonvielle, Matthieu,Mayer, Louis,Iannazzo, Laura,Arthur, Michel,Etheve-Quelquejeu, Mélanie,Braud, Emmanuelle
supporting information, p. 3542 - 3551 (2021/02/05)
The carbapenem class of β-lactams has been optimized against Gram-negative bacteria producing extended-spectrum β-lactamases by introducing substituents at position C2. Carbapenems are currently investigated for the treatment of tuberculosis as these drugs are potent covalent inhibitors of l,d-transpeptidases involved in mycobacterial cell wall assembly. The optimization of carbapenems for inactivation of these unusual targets is sought herein by exploiting the nucleophilicity of the C8 hydroxyl group to introduce chemical diversity. As β-lactams are structure analogs of peptidoglycan precursors, the substituents were chosen to increase similarity between the drug and the substrate. Fourteen peptido-carbapenems were efficiently synthesized. They were more effective than the reference drug, meropenem, owing to the positive impact of a phenethylthio substituent introduced at position C2 but the peptidomimetics added at position C8 did not further improve the activity. Thus, position C8 can be modified to modulate the pharmacokinetic properties of highly efficient carbapenems.
p-Nitrobenzyloxycarbonyl (pNZ) as a temporary Na-protecting group in orthogonal solid-phase peptide synthesis - Avoiding diketopiperazine and aspartimide formation
Isidro-Llobet, Albert,Guasch-Camell, Judit,Alvarez, Mercedes,Albericio, Fernando
, p. 3031 - 3039 (2007/10/03)
p-Nitrobenzyloxycarbonyl (pNZ) was used as a temporary protecting group for α-amino functionalities in solid-phase peptide synthesis. The corresponding derivatives are readily synthesized solids that perform well on solid phase. The pNZ moiety is orthogonal with the most common protecting groups used in peptide chemistry, and is removed under neutral conditions in the presence of catalytic amounts of acid. The use of pNZ derivatives in conjunction with Fmoc chemistry circumvents typical side reactions associated with the use of piperidine, such as DKP and aspartimide formation. The flexibility of pNZ can be exploited for the preparation of libraries of small organic molecules. Wiley-VCH Verlag GmbH & Co. KGaA, 2005.
2-thiosubstituted carbapenems
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, (2008/06/13)
Carbapenem antibiotic compounds of the general formula: STR1 wherein the moiety STR2 is a 4, 5 or 6 membered mono, di- or tri- substituted oxygen or sulfur containing ring; wherein Z is oxygen, sulfur, sulfoxide and sulfone, pharmaceutical compositions thereof useful for the treatment of bacterial infections, processes for preparing the compounds and new intermediates useful in the process.
