50737-35-4

Usage

Uses

Used in Pharmaceutical Research:
4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]pyridine is used as a key intermediate in the synthesis of new pharmaceutical compounds for various therapeutic areas. Its unique structure allows for the development of drugs with novel mechanisms of action and improved pharmacological properties.
Used in Agrochemical Development:
In the agrochemical industry, 4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]pyridine is utilized as a building block for the creation of new pesticides and agrochemicals. Its reactivity and structural features enable the design of molecules with enhanced pesticidal activity and selectivity.
Used in Material Science:
4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]pyridine is employed as a component in the development of advanced materials with specific properties. Its incorporation into polymers and other materials can lead to improved performance characteristics, such as thermal stability, mechanical strength, or chemical resistance.
Overall, 4-[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]pyridine is a versatile chemical with a wide range of potential applications across different industries, including pharmaceuticals, agrochemicals, and material science, due to its unique molecular structure and reactivity.

InChI:InChI=1/C8H6ClN3O/c9-5-7-11-8(12-13-7)6-1-3-10-4-2-6/h1-4H,5H2

Upstream product

• 1401223-73-1 C₈H₈ClN₃O₂ 
• 1594-57-6 pyridine-4-carboxamidoxime 
• 541-88-8 Chloroacetic anhydride 
• 1401223-73-1 (Z)-N'-(2-chloroacetoxy)isonicotinimidamide 
• 1594-57-6 isonicotinamidoxime 
• 100-48-1 pyridine-4-carbonitrile 

Downstream Products

• 1201042-18-3 (R)-3-((S)-2-phenyl-2-piperidin-1-yl-propionyloxy)-1-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-ylmethyl)-1-azonia-bicyclo[2.2.2]octane choride 
• 1401223-18-4 N-isopropyl-N-((3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl)methyl)-2-(p-tolyloxy)acetamide 

Relevant academic research and scientific papers

Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure

A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.

Oxadiazole-isopropylamides as potent and noncovalent proteasome inhibitors

Screening of the 50 000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited chymotrypsin-like (CT-L) activity (IC50 = 0.60 μM) with little effects on the other two major proteasome proteolytic activities, trypsin-like (T-L) and postglutamyl-peptide-hydrolysis-like (PGPH-L). LC-MS/MS and dialysis show that 1 is a noncovalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 = 27 nM). Detailed SAR studies indicate that the amide moiety and the two phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl in the para position (not ortho or meta) of the A-ring and a m-pyridyl group as B-ring, significantly improve activity. Compound 11ad (IC50 = 0.37 μM) is more potent than 1 (IC50 = 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further preclinical investigation of this class as noncovalent proteasome inhibitors.

PROTEASOME CHYMOTRYPSIN-LIKE INHIBITION USING PI-1833 ANALOGS

Focused library synthesis and medicinal chemistry on an oxadiazole- isopropylamide core proteasome inhibitor provided the lead compound that strongly inhibits CT-L activity. Structure activity relationship studies indicate the amide moiety and two phenyl rings are sensitive toward synthetic modifications. Only para-substitution in the A-ring was important to maintain potent CT-L inhibitory activity. Hydrophobic residues in the A-ring?s para-position and meta-pyridyl group at the B- ring significantly improved inhibition. The meta-pyridyl moiety improved cell permeability. The length of the aliphatic chain at the para position of the A-ring is critical with propyl yielding the most potent inhibitor, whereas shorter (i.e. ethyl, methyl or hydrogen) or longer (i.e. butyl, propyl and hexyl) chains demonstrating progressively less potency. Introduction of a stereogenic center next to the ether moiety (i.e. substitution of one of the hydrogens by methyl) demonstrated chiral discrimination in proteasome CT-L activity inhibition (the S-enantiomer was 35-40 fold more potent than the R-enantiomer)

1-AZA-BICYCLO [2.2.2] OCTANE DERIVATIVES USEFUL AS MUSCARINIC RECEPTOR ANTAGONISTS

The invention provides named compounds of formula (I), pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions and their use in therapy.