219117-92-7

Upstream product

• 6404-29-1 6-(tert-butoxycarbonylamino)hexanoic acid 
• 541-41-3 chloroformic acid ethyl ester 

Downstream Products

• 253877-76-8 N₁-(tert-butoxycarbonyl)-N₁₅-[(benzyloxy)carbonyl]-6-oxo-7-aza-1,15-pentadecanediamine 
• 446034-02-2 {5-[{8-[(6-tert-butoxycarbonylaminohexanoyl)(2-methoxybenzyl)amino]octyl}(2-methoxybenzyl)carbamoyl]pentyl}carbamic acid tert-butyl ester 
• 253877-77-9 N₁-(tert-butocycarbonyl)-N₂₂-[(benzyloxy)carbonyl]-6,17-dioxo-7,16-diaza-1,22-docosanediamine 
• 785042-21-9 14,23-bis-(2-methoxy-benzyl)-7,14,23,30-tetraaza-tricyclo[30.2.2.2^2,5]octatriaconta-1⁽³⁵⁾,2⁽³⁸⁾,3,5⁽³⁷⁾,32⁽³⁶⁾,33-hexaene-13,24-dione 
• 446033-83-6 6-amino-hexanoic acid {8-[(6-amino-hexanoyl)-(2-methoxy-benzyl)-amino]-octyl}-(2-methoxy-benzyl)-amide 

Relevant academic research and scientific papers

Synthesis and transdermal permeation-enhancing activity of ketone, amide, and alkane analogs of Transkarbam 12

Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium-5-(dodecyloxycarbonyl) pentylcarbamate, T12) is a highly active transdermal permeation enhancer. In this study, ketone, amide, and alkane analogs of T12 have been synthesized and evaluated for their permeation-enhancing activity using porcine skin and theophylline as a model drug. Replacement of ester by methylene and ketone, respectively, led to a significant decrease of activity. Amide analogs displayed lower activity in 60% propylene glycol and were comparable to T12 in isopropyl myristate. An intramolecular H-bond between ester and ammonium-carbamate group was suggested to be important for the permeation-enhancing activity of T12.

Design and Synthesis of Simplified Largazole Analogues as Isoform-Selective Human Lysine Deacetylase Inhibitors

Selective inhibition of KDAC isoforms while maintaining potency remains a challenge. Using the largazole macrocyclic depsipeptide structure as a starting point for developing new KDACIs with increased selectivity, a combination of four different simplified largazole analogue (SLA) scaffolds with diverse zinc-binding groups (for a total of 60 compounds) were designed, synthesized, and evaluated against class I KDACs 1, 3, and 8, and class II KDAC6. Experimental evidence as well as molecular docking poses converged to establish the cyclic tetrapeptides (CTPs) as the primary determinant of both potency and selectivity by influencing the correct alignment of the zinc-binding group in the KDAC active site, providing a further basis for developing new KDACIs of higher isoform selectivity and potency.

Structure-activity relationships of methoctramine-related polyamines as muscular nicotinic receptor noncompetitive antagonists. 3. Effect of inserting the tetraamine backbone into a macrocyclic structure

The present article expands on the study of another aspect of structure-activity relationships of the polymethylene tetraamines, namely, the effect of inserting the tetraamine backbone into a macrocyclic structure. To this end, compounds 8-12 were designed by linking the two terminal nitrogen atoms of prototype methoctramine 2 to an aryl moiety. Alternatively, 2 was first modified to achieve compounds 6 and 7, which in turn were cyclized by linking the two terminal primary amine functions to a polyphenyl spacer, affording 13-20. All the compounds were tested on muscle-type nAChRs and most of them as well on AChE. Furthermore, selected compounds were tested also on peripheral M2 and M3 mAChRs. All these cyclic derivatives, like prototypes, were potent noncompetitive antagonists at both frog and Torpedo nAChRs, suggesting that polyamines do not need to be linear or in extended conformation to optimally interact with the nicotinic channel; rather, they may bind in a U-shaped conformation. Relative to muscarinic activity, macrocyclic compounds 10, 13, 14, and 20, in contrast with the profile displayed by 2, were almost devoid of affinity. It is derived that an aryl spacer is detrimental to the interaction of polyamines with mAChRs. Finally, all the diamine diamides investigated in this study were much less potent in inhibiting AChE activity than prototype 3, suggesting that a macrocyclic structure may not be suitable for AChE inhibition.

Synthesis of two acridine conjugates of the bis(phenanthroline) ligand 'Clip-Phen' and evaluation of the nuclease activity of the corresponding copper complexes

The synthesis of three novel derivatives [N-acetyl-Clip-Phen (1), Clip- Phen-hexylaminoacridine (4) and Clip-Phen-hexylchloromethoxyaminoacridine (5)] of the bis(phenanthroline) ligand 'Clip-Phen', are described. Complexation of these ligands with copper(II) afforded the 1:1 complexes as hexafluorophosphate salts. The relaxation of φX 174 DNA was used as a DNA cleavage assay, with the following results. [Cu(1)]2+ was found to show a diminished activity relative to the parent complex [Cu(Clip-Phen)]2+. However, the acridine-containing complexes [Cu(4)H]3+ and [Cu(5)H]3+ exhibited significantly enhanced cleavage efficiencies, which has been attributed to increased affinity of the complexes for DNA. UV/Vis-spectral data of the complexes in the presence of calf-thymus DNA was consistent with an intercalative mode of binding.

Design, synthesis, and biological evaluation of symmetrically and unsymmetrically substituted methoctramine-related polyamines as muscular nicotinic receptor noncompetitive antagonists

The universal template approach to drug design foresees that a polyamine can be modified in such a way to recognize any neurotransmitter receptor. Thus, hybrids of polymethylene tetraamines and philanthotoxins, exemplified by methoctramine (1) and PhTX-343 (2), respectively, were synthesized to produce novel inhibitors of muscular nicotinic acetylcholine receptors. Polyamines 3-25 were synthesized and their biological profiles were evaluated at frog rectus abdominis muscle nicotinic receptors and guinea pig left atria (M2) and ileum longitudinal muscle (M3) muscarinic acetylcholine receptors. All of the compounds, like prototypes 1 and 2, were noncompetitive antagonists of nicotinic receptors while being, like 1, competitive antagonists at muscarinic M2 and M3 receptor subtypes. Interestingly, polyamines bearing a low number of methylenes between the nitrogen atoms, as in 3, 6, and 7, displayed a biological profile similar to that of 2: a noncompetitive antagonism at nicotinic receptors in the 7-25 μM range while not showing any antagonism for muscarinic receptors up to 10 μM. Increasing the number of methylenes separating these nitrogen atoms in methoctramine- related tetraamines resulted in a significant improvement in potency at nicotinic receptors. The most potent tetraamine was 19, bearing a 12 methylene spacer between the nitrogen atoms, which was 12-fold and 250-fold more potent than prototypes 1 and 2, respectively. Tetraamines 9-11, bearing a rather rigid spacer between the nitrogen atoms instead of the very flexible polymethylene chain, displayed a profile similar to that of 1 at nicotinic receptors, whereas a significant decrease in potency was observed at muscarinic M2 receptors. This finding may have relevance in understanding the mode of interaction with these receptors. Similarly, the constrained analogue 12 of methoctramine showed a decrease in potency at nicotinic and muscarinic M2 receptors, revealing that the tricyclic system, which incorporates the 2-methoxybenzylamine moiety of 1, does not represent a good pharmacophore for activity at these sites. A most intriguing finding was the observation that the photolabile tetraamine 22 was more potent than methoctramine at nicotinic receptors and, what is more important, it inhibited a closed state of the receptor.