Recent Advances in the Synthesis of Piperidones and Piperidines[J].
N2 - Novel extended side chain nitroimidazooxazine analogues featuring diverse linker groups between two aryl rings were studied as a potential strategy to improve solubility and oral activity against chronic infection by Mycobacterium tuberculosis. Both lipophilic and highly polar functionalities (e.g., carboxamide, alkylamine, piperazine, piperidine, but not sulfonamide) were well tolerated in vitro, and the hydrophilic linkers provided some solubility improvements, particularly in combination with pyridine rings. Most of the 18 compounds further assessed showed high microsomal stabilities, although in the acute infection mouse model, just one stilbene (6-fold) and two pyridine-containing acetylene derivatives (5-fold and >933-fold) gave in vivo efficacies notably superior to the clinical stage compound pretomanid (PA-824). The most efficacious analogue also displayed outstanding in vivo activity in the stringent chronic model (up to 24-fold better than the drug delamanid and 4-fold greater than our previous best phenylpyridine candidate), with favorable pharmacokinetics, including good oral bioavailability in the rat. (Chemical Equation Presented).
Synthesis of 3-alkyl-2-(4’-aryl)-6-phenylpiperidin-4-ones (1a-6a)
Naphthyridines constitute an important class of antibacterial agents, and upon the basis of this observation, we have reported the synthesis of a set of new 1,8-naphthyridines that were active against the M. tuberculosis H37Rv strain . Among these compounds 2, 7-di-(piperidin-1-yl)-4-phenyl-1,8-naphthyridine appeared to have a good activity with MIC of 6.25 µg/ml . Thus, as an extension of our research, we designed and synthesized a series of novel 1,8-naphthyridine derivatives which are of great potential interest that would be expected to provide highly desirable intermediates for the synthesis of new drug candidates.
The growing number of multidrug-resistant (MDR-TB) cases resulted in the need for the continuous discovery and development of new anti-tuberculosis entities. In this context, this paper focuses on the synthesis of potent compounds with minimum inhibitory concentration (MIC) in the micromolar range i.e., a very high activity when compared with our previously synthesized compounds which show an average MIC value of 6.25 µg/ml.
preparation of some derivatives of piperidine | …
Preparation of 2-(4'-methoxybenzylamine)-7-(piperidin-1-yl)-4-morpholinomethyl-1,8-naphthyridine (8) and 2-(4'-methoxybenzylamine)-6-nitro-7-(piperidin-1-yl)-4-morpholinomethyl-1,8-naphthyridine (9)
Piperidine Derivatives – Allchem Laboratories
It has been demonstrated  that the incomplete deprotection is associated with slow or incomplete coupling. In such cases, prolonged or repeated piperidine treatment, eventually associated with a change in solvent can help to reduce the problem.
Process for preparing 4-aryl-piperidine derivatives
The base catalyzed elimination of the suffhydryl protecting group affords dehydroalanine and the subsequent addition of piperidine yields the C-terminally modified peptide . This side reaction is minimized (but not avoided!) when trityl is used for the protection of the C-terminal Cys.
Patent US4254129 - Piperidine derivatives - Google …
The addition of HOBt to the piperidine solution helps to reduce the formation of aspartimide. Another approach is to introduce the residue preceeding Asp as the Fmoc(Hmb) protected amino acid .
This invention relates to novel substituted piperidine derivatives
Several examples of aspartimide formation during the peptide elongation have been reported, together with the reopening of the aspartimide cycle during the subsequent Fmoc deprotection step, yielding piperidides [64,65,66].
Synthesis of piperidine derivatives fused to a tetrahydrofuran ring
The other approach is to introduce backbone protecting groups which will prevent the formation of hydrogen bonds. Such protection is made by the introduction of the Hmb group on the αnitrogen . It has been shown that the presence of a Hmb unit every 6-7 residues is sufficient to disrupt the peptide aggregation . The Hmb protected amino acid is introduced under the form of N,O-bis-Fmoc-N-(2hydroxy-4-methoxybenzyl) derivative, the O-Fmoc protection being cleaved during the following piperidine treatment. At the end of the synthesis the Hmb group is cleaved in the final TFA cleavage.