70067-45-7

Usage

Uses

Used in Pharmaceutical Industry:
Pyridine, 4-isocyanatois used as a key intermediate in the synthesis of thiadiazolopiperazinyl ureas, which are inhibitors of fatty acid amide hydrolase (FAAH). These inhibitors have potential applications in the treatment of various disorders, including pain, inflammation, and neurodegenerative diseases, by modulating the endocannabinoid system.
Used in Medicinal Chemistry Research:
Pyridine, 4-isocyanatois used as a building block in the preparation of pyridyl-substituted pyrazolotriazolopyrimidine derivatives. These compounds have been found to act as water-soluble human A3 adenosine receptor antagonists. The A3 adenosine receptor plays a role in various physiological processes, and its modulation can have therapeutic benefits in conditions such as asthma, chronic obstructive pulmonary disease (COPD), and other inflammatory disorders.

Upstream product

• 4013-73-4 isonicotinoyl azide 
• 504-24-5 4-aminopyridine 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 55-22-1 pyridine-4-carboxylic acid 

Downstream Products

• 1333245-13-8 1,3,5-triethyl-2,4,6-tris[3-{3-(4-pyridyl)ureido}-phenoxymethyl]benzene 
• 1036740-19-8 C₁₈H₂₂N₄O 
• 1036740-22-3 C₂₃H₃₀N₄O₄ 
• 897025-54-6 1-[8-(2-benzyloxy-ethyl)-2-furan-2-yl-8H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-yl]-3-pyridin-4-yl-urea 

Relevant academic research and scientific papers

Coordination polymers derived from a flexible bis(pyridylurea) ligand: Conformational change of the ligand and structural diversity of the complexes

The assembly of a bis(pyridylurea) ligand, N,N′-ethane-1,2-diylbis(3- pyridin-4-ylurea) (L), with Zn(AcO)2, CdCl2, CdSO 4 or CuSO4 led to four coordination polymers, {[Zn(AcO)2L]·H2O·CH3OH} n (1), {[CdCl2L2]·2DMF}n (2), {[CdSO4L(H2O)3]·3H2O} n (3), and {[CuSO4L(H2O)2] ·2H2O}n (4). Compound 1 is an infinite 1D zigzag chain with alternate Zn(AcO)2 units and L molecules. The cadmium(ii) dichloro complex 2 features a corrugated sheet structure with a (4,4) net topology, while the sulfato complex 3 shows a unique 1O/2U interwoven 3D structure assembled from zigzag chains. The copper(ii) complex 4 is an exceptional diamondoid network with an unusual 12-fold [6 + 6] interpenetration mode. Interestingly, the ligand shows the expected flexibility in the formation of the coordination polymers. In 1, 3 and 4, the central ethylene spacer adopts the anti conformations and is roughly linear, whereas in 2 it assumes a gauche form and exists as a V-shaped linker. The structural variation of these coordination polymers as well as the conformational change of the ligand in the presence of different counter anions and metal ions is discussed.

Anchoring Drugs to a Zinc(II) Coordination Polymer Network: Exploiting Structural Rationale toward the Design of Metallogels for Drug-Delivery Applications

A new series of coordination polymers (CPs) were synthesized and crystallographically characterized by single-crystal X-ray diffraction with the aim of developing drug-delivery systems via metallogel formation. Structural rationale was employed to design such coordination-polymer-based metallogels. As many as nine CPs were obtained by reacting two bis(pyridyl)urea ligands, namely, 1,3-dipyridin-3-ylurea (3U) and 1,3-dipyridin-4-ylurea (4U), and the sodium salt of various nonsteroidal antiinflammatory drugs, namely, ibuprofen (IBU), naproxen (NAP), fenoprofen (FEN), diclofenac (DIC), meclofenamic acid (MEC), mefenamic acid (MEF), and Zn(NO3)2. All of the CPs displayed 1D polymeric chains that were self-assembled through various hydrogen-bonding interactions involving the urea N-H and carboxylate O atoms and, in a few cases, lattice-occluded water molecules. The reacting components of the CPs produced five metallogels in dimethyl sulfoxide/water. The gels were characterized by rheology and transmission electron microscopy. Three selected metallogelators, namely, 3UMEFg, 3UNAPg, and 3UMECg, showed in vitro anticancer, cell imaging, and multidrug delivery for antibacterial applications, respectively. The shear-thinning properties of 3UMECg (rheoreversibility and injectability) make it a potential candidate for plausible topical application.

Making and breaking of gels: Stimuli-responsive properties of bis(pyridyl-n-oxide urea) gelators

The structural modification of existing supramolecular architecture is an efficient strategy to design and synthesize supramolecular gels with tunable and predictable properties. In this work, we have modified bis(pyridyl urea) compounds with different linkers, namely hexylene and butylene, to their corresponding bis(pyridyl-N-oxide urea). The gelation properties of both the parent and the modified compounds were studied, and the results indicated that modification of the 3-pyridyl moieties to the corresponding 3-pyridyl-N-oxides induced hydrogelation. The stability of the parent and modified compounds were evaluated by sol-gel transition temperature (Tgel ) and rheological measurements, and single-crystal X-ray diffraction was used to analyze the solid-state interactions of the gelators. The morphologies of the dried gels were analyzed by scanning electron microscopy (SEM), which revealed that the structural modification did not induce any prominent effect on the gel morphology. The stimuli-responsive behavior of these gels in the presence of salts in DMSO/water was evaluated by rheological experiments, which indicated that the modified compounds displayed enhanced gel strength in most cases. However, the gel network collapsed in the presence of the chloride salts of aluminum(III), zinc(II), copper(II), and cadmium(II). The mechanical strength of the parent gels decreased in the presence of salts, indicating that the structural modification resulted in robust gels in most cases. The modified compounds formed gels below minimum gel concentration in the presence of various salts, indicating salt-induced gelation. These results show the making and breaking ability of the gel network in the presence of external stimuli (salts), which explains the potential of using LMWGs based on N-oxide moieties as stimuli-responsive materials.

Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus

Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC50 = 0.78–22.4 μM) on the motility and development of parasitic stages of H. contortus, and which were found to be highly selective in a mammalian cell counter-screen. These compounds could be used as suitable chemical tools for drug target identification or as lead compounds for further optimization.

S1PR2 inhibitors potently reverse 5-FU resistance by downregulating DPD expression in colorectal cancer

In this study, S1PR2 was reckoned as a brand-new GPCR target for designing inhibitors to reverse 5-FU resistance. Herein a series of pyrrolidine pyrazoles as the S1PR2 inhibitors were designed, synthesized and evaluated for their activities of anti-FU-resistance. Among them, the most promising compound JTE-013, exhibited excellent inhibition on DPD expression and potent anti-FU-resistance activity in various human cancer cell lines, along with the in vivo HCT116DPD cells xenograft model, in which the inhibition rate of 5-FU was greatly increased from 13.01percent–75.87percent. The underlying mechanism was uncovered that JTE-013 demonstrated an anti-FU-resistance activity by blocking S1PR2 internalization to the endoplasmic reticulum (ER), which inhibited the degradation of 5-FU into α-fluoro-β-alanine (FBAL) by downregulating tumoral DPD expression. Overall, JTE-013 could serve as the lead compound for the discovery of new anti-FU-resistance drugs. Significance: This study provides novel insights that S1PR2 inhibitors could sensitize 5-FU therapy in colorectal cancer.

Spectroscopic Characterization of Nicotinoyl and Isonicotinoyl Nitrenes and the Photointerconversion of 4-Pyridylnitrene with Diazacycloheptatetraene

Recently, nicotinoyl nitrene (2) has been generated from the photodecomposition of nicotinoyl azide (1) and used as the key intermediate in probing nucleobase solvent accessibility inside cells. Following the 266 nm laser photolysis of nicotinoyl azide (1) and isonicotinoyl azide (5) in solid N2 matrices at 15 K, nicotinoyl nitrene (2) and isonicotinoyl nitrene (6) have now been identified by matrix-isolation infrared (IR) spectroscopy. Both aroyl nitrenes 2 and 6 adopt closed-shell singlet ground states stabilized by significant Nnitrene···O interactions, which is consistent with the spectroscopic analysis and calculations at the CBS-QB3 level of theory. Upon subsequent visible light irradiations, 2 (400 ± 20 nm) and 6 (532 nm) undergo rearrangement to pyridyl isocyanates 3 and 7. Further dissociation of 3 and 7 under 193 nm laser irradiation results in CO elimination and formation of ketenimines 12 and 13 via the ring opening of elusive pyridyl nitrenes 4 and 8, respectively. In addition to the IR spectroscopic identification of 8 in the triplet ground state, its reversible photointerconversion with ring expansion to diazacycloheptatetraene 9 has been observed directly. The spectroscopic identification of the nitrene intermediates was aided by calculations at the B3LYP/6-311++G(3df,3pd) level, and the mechanism for their generation in stepwise decompositions of the azides is discussed in the light of CBS-QB3 calculations.

Synthesis and crystal structures of metallomacrocyclic and helical Hg(II) complexes with two bis(pyridylurea) ligands

Two complexes, [Hg2L12Cl4]·2DMF (1) and {[HgL2Br2]·2DMSO}n (2), have been synthesized and characterized from two flexible bis(pyridylurea) ligands (L1 and L2) with mercury(II) halides respectively. In the two complexes, both Hg(II) centers adopt four-coordination mode, but they present different architectures with slightly adjusted 3- and 4-position of nitrogen atom in the pyridyl ring. Complex 1 exists as a centrosymmetric metallamacrocycle with L1 as bidentate ligand bridging two HgCl2 units, and complex 2 exists as a 1D helical chain coordination polymer with L2 as bridging ligand and Br? as terminal ligand, which indicates that the nature of the ligand plays an important role in the coordination networks.

Bilobalide B derivative and application of bilobalide B derivative in medicine

The invention relates to a new bilobalide B derivative, hydrate, solvate or pharmacy-acceptable salt of the bilobalide B derivative, and a medicine composition with the derivative, and further relates to application of the compound or the medicine composition in preparation of medicine. The medicine is used for preventing, processing, treating or relieving cardiovascular and cerebrovascular diseases of patients. The invention further relates to a preparation method of the bilobalide B derivative.

Photolysis and thermolysis of pyridyl carbonyl azide monolayers on single-crystal platinum

The photochemical and thermal reactivity of a number of acyl azide-substituted pyridine compounds, namely nicotinyl azide, isonicotinyl azide, picolinyl azide and dinicotinyl azide with investigated as saturated monolayers on a single-crystal Pt(111) surface in an ultrahigh vacuum chamber. Multilayers of the substrates exhibited a maximum rate of desorption at 270 K, above which, stable saturated monolayers formed as characterized by reflection-absorption infrared spectroscopy by observation of C=O and N 3 bands at 1700 cm-1, and 2100 and 1300 cm-1 respectively. The monolayers were stable up to 400 K. Photolysis of the monolayer (or heating above 400 K) results in the formation of the respective isocyanate intermediate after loss of nitrogen as evidenced by the appearance of a new infrared band at 2260 cm-1 with concomitant loss of the azide bands. The resulting isocyanate saturated monolayer is stable in absence of nucleophiles, but can be quenched with appropriate nucleophiles. Saturated monolayers of a number of acyl azide-substituted pyridine compounds, namely nicotinyl azide, isonicotinyl azide, picolinyl azide and dinicotinyl azide, were formed on single-crystal Pt(111) surfaces in a UHV chamber. These monolayers were characterized by RAIR and thermal programmed desorption. Photolysis or thermolysis of these saturated monolayers leads to the corresponding isocyanate via a Curtius rearrangement.

Construction of two- or three-component low molecular weight gel systems

Pyridyl group-bound tris-urea 2, whose structure issimilar to the tris-urea low molecular weight gelator (LMWG) 1, was synthesized. Addition of a trace amount of 2 and Pd(OAc)2 to 1 resulted in a reduction in the critical gelation concentration (CGC) in acetone. Metal-ligand interaction between Pd(OAc)2 and the pyridyl group of 2 assist the gelation. Assistance by intermolecular hydrogen bonding was also effective for gelation of acetone. An acetone gel of 1 was formed at half the value of the CGC of 1 alone by adding a trace amount of 2 and isophthalicacid. Scanning electron microscopy (SEM) measurements of these aggregates showed structural alterations caused by the additive. A mixture of 1 and a trace amount of 2 in EtOAc gave a gel. Addition of 2 was essential to form the gel, because 1 alone did not gel EtOAc. SEM measurements indicated that 2 produced extension of the fibrous aggregates.