757949-48-7

Upstream product

• 108-91-8 cyclohexylamine 
• 498-94-2 isonipecotic acid 
• 280115-99-3 tert-butyl 4-(chlorocarbonyl)-piperidine-1-carboxylate 
• 84358-13-4 N-[(tert-butoxy)carbonyl]piperidine-4-carboxylic acid 
• 108-85-0 1-bromocyclohexane 
• 91419-48-6 4-carbamoyl-piperidine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 63214-55-1 piperidine-4-carboxylic acid cyclohexylamide 
• 1019851-98-9 piperidine-4-carboxylic acid cyclohexylamide hydrochloride 

Relevant academic research and scientific papers

SULFONAMIDE COMPOUNDS AND THE USE THEREOF IN THE TREATMENT OF CANCER

The present disclosure relates generally to a class of sulfonamide-based compounds, compositions containing the same and the therapeutic use of the compounds in the treatment of cancer.

Nickel-catalyzed transamidation of aliphatic amide derivatives

Transamidation, or the conversion of one amide to another, is a long-standing challenge in organic synthesis. Although notable progress has been made in the transamidation of primary amides, the transamidation of secondary amides has remained underdeveloped, especially when considering aliphatic substrates. Herein, we report a two-step approach to achieve the transamidation of secondary aliphatic amides, which relies on non-precious metal catalysis. The method involves initial Boc-functionalization of secondary amide substrates to weaken the amide C-N bond. Subsequent treatment with a nickel catalyst, in the presence of an appropriate amine coupling partner, then delivers the net transamidated products. The transformation proceeds in synthetically useful yields across a range of substrates. A series of competition experiments delineate selectivity patterns that should influence future synthetic design. Moreover, the transamidation of Boc-activated secondary amide derivatives bearing epimerizable stereocenters underscores the mildness and synthetic utility of this methodology. This study provides the most general solution to the classic problem of secondary amide transamidation reported to date.

Improving selectivity preserving affinity: New piperidine-4-carboxamide derivatives as effective sigma-1-ligands

We report the design, synthesis and binding evaluation against 1 and 2 receptors of a series of new piperidine-4-carboxamide derivatives variously substituted on the amide nitrogen atom. Specifically, we assessed the effects exerted on receptor affinity by substituting the N-benzylcarboxamide group present on a series of compounds previously synthesized in our laboratory with different cyclic or linear moieties. The synthesized compounds 2a-o were tested to estimate their affinity and selectivity toward 1 and2 receptors. Very high 1 affinity (Ki Combining double low line 3.7 nM) and Ki2/Ki1 selectivity ratio (351) were found for the tetrahydroquinoline derivative 2k, featuring a 4-chlorobenzyl moiety linked to the piperidine nitrogen atom.

Photoinduced, copper-catalyzed alkylation of amides with unactivated secondary alkyl halides at room temperature

The development of a mild and general method for the alkylation of amides with relatively unreactive alkyl halides (i.e., poor substrates for S N2 reactions) is an ongoing challenge in organic synthesis. We describe herein a versatile transition-metal-catalyzed approach: in particular, a photoinduced, copper-catalyzed monoalkylation of primary amides. A broad array of alkyl and aryl amides (as well as a lactam and a 2-oxazolidinone) couple with unactivated secondary (and hindered primary) alkyl bromides and iodides using a single set of comparatively simple and mild conditions: inexpensive CuI as the catalyst, no separate added ligand, and C-N bond formation at room temperature. The method is compatible with a variety of functional groups, such as an olefin, a carbamate, a thiophene, and a pyridine, and it has been applied to the synthesis of an opioid receptor antagonist. A range of mechanistic observations, including reactivity and stereochemical studies, are consistent with a coupling pathway that includes photoexcitation of a copper-amidate complex, followed by electron transfer to form an alkyl radical.

Novel benzoxazole inhibitors of mPGES-1

A novel series of potent benzoxazole mPGES-1 inhibitors has been derived from a hit from a high throughput screen. Compound 37 displays mPGES-1 inhibition in an enzyme assay (0.018 μM) and PGE-2 inhibition in a cell-based assay (0.034 μM). It demonstrates 500- and 2500-fold selectivity for mPGES-1 over COX-2 and 6-keto PGF-1α, respectively. In vivo PK studies in dogs demonstrate 55% oral bioavailability and an 7 h half-life.