58859-77-1

Upstream product

• 345-17-5 1-chloro-4-fluoro-2-nitrobenzene 
• 182365-86-2 tert-butyl 4-(5-fluoro-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-1-yl)piperidine-1-carboxylate 
• 1004304-10-2 tert-butyl 4-((2-amino-4-fluorophenyl)amino)piperidine-1-carboxylate 
• 87120-72-7 1-(tert-butoxycarbonyl)-4-aminopiperidine 
• 107618-33-7 4-(5-fluoro-2-oxo-2,3-dihydro-benzoimidazol-1-yl)-piperidine-1-carboxylic acid ethyl ester 
• 58859-46-4 ethyl 4-aminopiperidine-1-carboxylate 
• 364-74-9 1,4-difluoro-2-nitrobenzene 
• 107618-14-4 4-(4-fluoro-2-nitro-phenylamino)-piperidine-1-carboxylic acid ethyl ester 
• 107618-21-3 4-(2-amino-4-fluoro-phenylamino)-piperidine-1-carboxylic acid ethyl ester 

Downstream Products

• 1074762-31-4 C₂₅H₃₁FN₄O 
• 1074762-34-7 C₂₅H₂₈F₄N₄O 
• 1092545-60-2 C₂₃H₂₇FN₄O₃S 
• 58859-78-2 1-{1-[4,4-bis-(4-fluoro-phenyl)-butyl]-piperidin-4-yl}-5-fluoro-1,3-dihydro-benzoimidazol-2-one 
• 521174-83-4 1-[1-(4-butyl-benzoyl)-piperidin-4-yl]-5-fluoro-1,3-dihydro-benzoimidazol-2-one 

Relevant academic research and scientific papers

Optimization of a Series of Mu Opioid Receptor (MOR) Agonists with High G Protein Signaling Bias

While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal βarrestin-mediated signaling because MOR agonist-treated βarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/βarr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.

Synthesis and SAR of analogues of the M1 allosteric agonist TBPB. Part I: Exploration of alternative benzyl and privileged structure moieties

This Letter describes the first account of the synthesis and SAR, developed through an iterative analogue library approach, of analogues of the highly selective M1 allosteric agonist TBPB. With slight structural changes, mAChR selectivity was maintained, but the degree of partial M1 agonism varied considerably.

Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists: Optimization of the 4-substituted piperidine

In our continuing effort to identify CGRP receptor antagonists for the acute treatment of migraine, we have undertaken a study to evaluate alternative 4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone structures which, when incorporated into the benzodiazepine core, afford potent CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent analog (18) which overcomes the instability issues associated with the lead structure 1. A general pharmacophore for the 4-substituted piperidine component of these CGRP receptor antagonists is also presented.

TRIAZOLE DERIVATIVES AS VASOPRESSIN ANTAGONISTS

Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: R1 represents a group selected from H, CF3, and C1-6 alkyl (optionally substituted by C1-6 alkyloxy or triazolyl); R2/

Piperidines

Compounds, compositions and methods are provided which are useful in the treatment of diseases through the inhibition of sodium ion flux through voltage-dependent sodium channels. More particularly, the invention provides substituted piperidines, and compositions containing these compounds. Also provided are methods using the compounds of the invention for the treatment of central or peripheral nervous system disorders, particularly pain and chronic pain by blocking sodium channels associated with the onset or recurrance of the indicated conditions. The compounds, compositions and methods of the present invention are of particular use for treating neuropathic or inflammatory pain by the inhibition of ion flux through a channel that includes a PN3 subunit.

alpha 1a adrenergic receptor antagonists

This invention relates to novel compounds, their synthesis and use as selective alpha 1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the alpha 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.

Alpha 1a adrenergic receptor antagonists

This invention relates to novel compounds, their synthesis and use as selective α 1a adrenergic receptor antagonists. One application of the compounds is in the treatment of benign prostatic hyperplasia. The compounds are selective in their ability to relax smooth muscle tissue enriched in the α 1a receptor subtype without at the same time inducing hypotension. One such tissue is found surrounding the urethral lining. Therefore, one utility of the instant compounds is to provide acute relief to males suffering from benign prostatic hyperplasia, by permitting less hindered urine flow. Another utility of the instant compounds is provided by combination with a human 5-alpha reductase inhibitory compound, such that both acute and chronic relief from the effects of benign prostatic hyperplasia are achieved.