5264-02-8

Upstream product

• 2629-72-3 4-(3-Hydroxypropyl)pyridine 
• 110-86-1 pyridine 
• 59137-44-9 3-carboxy-2-(pyridin-1-ium-1-yl)propanoate 
• 108-89-4 picoline 
• 107-04-0 1-Bromo-2-chloroethane 

Downstream Products

• 84200-09-9 4-(3-cyanopropyl)pyridine 
• 405939-75-5 (6-{5-[tert-butoxycarbonyl-(3-pyridin-4-yl-propyl)-amino]-pyridin-3-yl}-pyrazin-2-yl)-(4-chloro-phenyl)-carbamic acid tert-butyl ester 
• 405939-17-5 (6-{5-[tert-butoxycarbonyl-(3-pyridin-4-yl-propyl)-amino]-pyridin-3-yl}-pyrazin-2-yl)-(3,4-dichloro-phenyl)-carbamic acid tert-butyl ester 
• 118892-71-0 cis-4-(3-phosphonoprop-1-yl)piperidine-2-carboxylic acid 
• 5264-15-3 4-(4-pyridinyl)butan-1-ol 
• 189938-86-1 N-(4-Pyridin-4-yl-butyl)-acetamide 
• 145301-48-0 BIBN 99 
• 102878-73-9 γ-(pyridin-4-yl)butyric acid 

Relevant academic research and scientific papers

Practical and Regioselective Synthesis of C-4-Alkylated Pyridines

The direct position-selective C-4 alkylation of pyridines has been a long-standing challenge in heterocyclic chemistry, particularly from pyridine itself. Historically this has been addressed using prefunctionalized materials to avoid overalkylation and mixtures of regioisomers. This study reports the invention of a simple maleate-derived blocking group for pyridines that enables exquisite control for Minisci-type decarboxylative alkylation at C-4 that allows for inexpensive access to these valuable building blocks. The method is employed on a variety of different pyridines and carboxylic acid alkyl donors, is operationally simple and scalable, and is applied to access known structures in a rapid and inexpensive fashion. Finally, this work points to an interesting strategic departure for the use of Minisci chemistry at the earliest possible stage (native pyridine) rather than current dogma that almost exclusively employs Minisci chemistry as a late-stage functionalization technique.

Discovery of Potent Human Glutaminyl Cyclase Inhibitors as Anti-Alzheimer’s Agents Based on Rational Design

Glutaminyl cyclase (QC) has been implicated in the formation of toxic amyloid plaques by generating the N-terminal pyroglutamate of β-amyloid peptides (pGlu-Aβ) and thus may participate in the pathogenesis of Alzheimer’s disease (AD). We designed a library of glutamyl cyclase (QC) inhibitors based on the proposed binding mode of the preferred substrate, Aβ3E?42. An in vitro structure-activity relationship study identified several excellent QC inhibitors demonstrating 5- to 40-fold increases in potency compared to a known QC inhibitor. When tested in mouse models of AD, compound 212 significantly reduced the brain concentrations of pyroform Aβ and total Aβ and restored cognitive functions. This potent Aβ-lowering effect was achieved by incorporating an additional binding region into our previously established pharmacophoric model, resulting in strong interactions with the carboxylate group of Glu327 in the QC binding site. Our study offers useful insights in designing novel QC inhibitors as a potential treatment option for AD.

AZETIDINE COMPOUND AND PHARMACEUTICAL USE THEREOF

Compounds of formula [I]: wherein each symbol is as defined in the description, or a pharmaceutically acceptable salts or solvates thereof.

Nα-Imidazolylalkyl and Pyridylalkyl Derivatives of Histaprodifen: Synthesis and in Vitro Evaluation of Highly Potent Histamine H1-Receptor Agonists

A novel series of Nα-imidazolylalkyl and pyridylalkyl derivatives of histaprodifen (6, 2-[2-(3,3-diphenylpropyl)imidazol-4-yl]ethanamine) was synthesized and evaluated as histamine H1-receptor agonists. The title compounds displayed partial agonism at contractile H1-receptors of guinea pig ileum and were at least equipotent with histamine. Agonist effects of the new derivatives were susceptible to blockade by the H1-receptor antagonist mepyramine (2-100 nM). In the imidazole series, suprahistaprodifen (51, [2-[2-(3,3-diphenylpropyl)-1H-imidazol-4-yl]ethyl]-[2-(1H-imidazol-4-yl) ethyl]amine, Nα-2-[(1H-imidazol-4-yl)ethyl]histaprodifen) showed the highest H1-receptor agonist potency ever reported in the literature (pEC50 8.26, efficacy Emax 96%). Elongation of the alkyl spacer from ethyl to butyl decreased activity from 3630% (ethyl, 51) to 163% (butyl, 53) of histamine potency. The exchange of the terminal imidazole nucleus for a pyridine ring resulted in compounds with comparably high potency. A decrease in agonist potency and efficacy was observed when the attachment of the alkyl spacer was consecutively changed from the ortho to the meta and the para position, respectively, of the pyridine ring. The pyridine series that contained a butyl chain possessed the highest potency and affinity. Nα-[4-(2-pyridyl)butyl]histaprodifen (56) emerged as a strong partial agonist, being almost equipotent with 51 (pEC50 8.16, E max 89%). Compounds 51 and 56 also showed potent partial agonism at contractile H1 receptors in guinea pig aorta and potently activated H1-receptor-mediated endothelium-dependent relaxation in the rat aorta. Compounds 51-65 displayed low to moderate affinity at H2, H3, and M3 receptors in functional models of guinea pig. Collectively, Nα-imidazolylalkyl- and Nα -pyridylalkyl-substituted histaprodifens represent a novel class of potent H1-receptor agonists. These compounds may be useful to define the (patho)physiological role of the H1-receptor and refine molecular models of H1-receptor activation.

Fibrinogen receptor antagonists

Fibrinogen receptor antagonists having the structure, for example, of STR1 for example STR2

Synthesis and evaluation of halogenated dibenzodiazepines as muscarinic receptor ligands

Syntheses of four novel amide analogues of the muscarinic M2 receptor antagonists, DIBA and BIBN 140, are described from a common intermediate. Pharmacological evaluation through in vitro assays reveals high muscarinic receptor affinity in each of the compounds, but variable subtype selectivity, primarily M2 but in one case M3.

Substituted dibenzoxazepine and dibenzthiazepine carbamate compounds, pharmaceutical compositions and methods of use

The present invention provides substituted dibenzoxazepine and dibenzthiazepine compounds of Formula I: STR1 which are useful as analgesic agents for the treatment of pain, pharmaceutical compositions comprising a therapeutically-effective amount of a com

Substituted dibenzoxazepine and dibenzthiazepine urea compounds, pharmaceutical compositions and methods of use

The present invention provides substituted dibenzoxazepine and dibenzthiazepine compounds of Formula I: STR1 which are useful as analgesic agents for the treatment of pain, pharmaceutical compositions comprising a therapeutically-effective amount of a com

Substituted imidazo[1,5-A]pyridines

Disclosed are e.g. novel 5-(carboxyalkyl)imidazo[1,5-a]pyridines, their derivatives and methods of synthesis. Said compounds are useful as selective thromboxane synthetase inhibitors for the treatment of diseases such as cerebral ischaemia, shock, thrombo