No abstract

Redx Pharma has discovered a novel series of topoisomerase inhibitors that are being further developed for drug-resistant bacteria.

Shrimp disease management using bioactive marine secondary metabolites (MSMs) was developed as a package of practice for the sustainable shrimp farming. Therefore, the effect of MSMs on the host defense factors of shrimp was evaluated in the present study. Findings indicated that Ulva diet significantly increase the defense factors such as haemogram, agglutination index, phagocytic rate, bacterial clearance and serum bactericidal activity of treated shrimps over the control group. Based on the gut bacterial load, Ulva diet was considered as proactive drug whereas Dendrilla diet was determined as a curative agent. D

An efficient four-step synthesis (requiring no purification) of Boc-protected 4,4¢-dipiperidinyl ethers is described.The design of new ligands for clinical and pharmacological profiling of key targets of biological interest, in particular for disease areas of unmet medical need, is an important goal for the pharmaceutical industry. As part of a program directed towards finding novel histamine-subtype-selective ligands, we identified the novel 4,4¢-dipiperidinyl ether template 1 which showed unexpected potency at the histamine H 3 receptor. 1 Surprisingly, this simple ether template was relatively unknown at the commencement of our studies. 2 For example, we found no reference to the parent diamine, and scarce reports of saturated 4,4¢-dipiperidinyl ethers of any substitution in the last 100 years. First reported in 1909, 2a the 2,2¢,6,6¢-tetraphenyl decorated compound 2 was a side product from condensation chemistry of acetophenones ( Figure 1). The bistropyl ether 3 is known, 2b which contains the 4,4¢-dipiperidinyl ether as a fragment of the structure. In addition, N-methyldipiperidinyl ether is found as a spacer group in a series of bicyclic pyrimidine anti-inflammatory agents 4. 2c,3 A recent paper by Chao et al. highlighted this deficit and reported the synthesis of a series of piperidine containing bis-N-heterocyclic amine ethers by Mitsunobu reaction followed by acid-catalysed pyridyl reduction. 4a Our findings are reported herein. Figure 1 Examples of dipiperidinyl ethersOur synthesis of the previously unknown ether 9 began by coupling hydroxy piperidine 5 with 4-chloropyridine, followed by formation of the quaternary alkylammonium salt 7, under standard conditions (Scheme 1). 5 A simple one-pot reduction of the pyridine (step c) then gave dipiperidine ether 8. Subsequent Boc deprotection afforded 9 which allowed further elaboration of the template by functionalisation of the secondary amine. Scheme 1 Reagents and conditions: (a) 4-chloropyridine·HCl, NaH (60% dispersion), DMSO, 70°C (79%); (b) i-PrI, CH 2 Cl 2 , r.t. (quant.); (c) LiBH 4 , ammonium formate, 10% Pd/C, MeOH, reflux; (d) TFA, r.t. then 1 M HCl (93% over 2 steps). Alternative conditions: (c) PtO 2 , H 2 (3.45 bar, r.t.), EtOH, 6 d (54% 8 + approximately 20% 5 due to ether cleavage); or (c) i. NaBH 4 , MeOH; ii. ammonium formate, 10% Pd/C, MeOH, reflux (66%).This initial strategy was encouraging but capricious yields in the reduction step led us to explore alternative approaches. Stepwise reduction of 7 using NaBH 4 in MeOH followed by transfer hydrogenation afforded 8 in reasonable yield. More concisely, 8 could be obtained by direct hydrogenation of 7, although yields were modest and variable, and significant ether cleavage was observed.

The discovery of novel tricyclic topoisomerase inhibitors (NTTI's) that address fluoroquinolone resistance.