36932-61-3

Usage

Derivative of isoindole-1,3(2H)-dione

The chemical is derived from the parent compound isoindole-1,3(2H)-dione, which is a heterocyclic compound.

2-(6-methyl-2-pyridinyl) substituent

The compound has a specific substituent group attached to the isoindole-1,3(2H)-dione core, which is a 6-methyl-2-pyridinyl group.

Heterocyclic compound

The compound has a cyclic structure containing both oxygen and nitrogen atoms, making it a heterocyclic compound.

Pharmaceutical industry application

The compound is used in the pharmaceutical industry for the synthesis of various drugs.

Potential in medicinal chemistry

The compound has potential applications in the field of medicinal chemistry, possibly leading to the development of new therapeutic agents.

Biological activity

The compound may exhibit biological activity, making it of interest for further research in the development of new therapeutic agents.

Upstream product

• 1824-81-3 2-Amino-6-methylpyridine 
• 85-44-9 phthalic anhydride 

Downstream Products

• 83592-42-1 2-(6-bromomethylpyridin-2-yl)isoindole-1,3-dione 
• 79651-64-2 (6-Amino-pyridin-2-yl)-methanol 
• 193470-31-4 6-(methylamino)methyl-2-pyridinamine 
• 848678-65-9 imidazo[1,5-a]pyridin-5-amine 
• 85230-39-3 2-amino-6-(2-phenylethyl)pyridine 
• 934537-48-1 2-(6-phenethylpyridin-2-yl)isoindole-1,3-dione 

Relevant academic research and scientific papers

Design, synthesis, and biological activity evaluation of BACE1 inhibitors with antioxidant activity

The proteolytic enzyme β-secretase (BACE1) plays a central role in the synthesis of the pathogenic β-amyloid peptides (Aβ) in Alzheimer's disease (AD), antioxidants could attenuate the AD syndrome and prevent the disease progression. In this study, BACE1 inhibitors (D1–D18) with free radical-scavenging activities were synthesized by molecular hybridization of 2-aminopyridine with natural antioxidants. The biological activity evaluation showed that D1 had obvious inhibitory activity against BACE1, and strong antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS+?) assay, which could be used as a lead compound for further study.

Gear up for a pH shift: A responsive iron(II) 2-amino-6-picolyl-appended macrocyclic paraCEST agent that protonates at a pendent group

Two high-spin Fe(II) and Co(II) complexes of 1,4,7,10-tetraazacyclododecane (CYCLEN) appended with four 2-amino-6-picolyl groups, denoted as [Fe(TAPC)]2+ and [Co(TAPC)]2+, are reported. These complexes demonstrate C2-symmetrical geometry from coordination of two pendents, and they are present in a single diastereomeric form in aqueous solution as shown by 1H NMR spectroscopy and by a single-crystal X-ray structure for the Co(II) complex. A highly shifted but low-intensity CEST (chemical exchange saturation transfer) signal from NH groups is observed at -118 ppm for [Co(TAPC)]2+ at pH 6.0 and 37 °C. A higher intensity CEST peak is observed for [Fe(TAPC)]2+, which demonstrates a pH-dependent frequency shift from -72 to -79 ppm at pH 7.7 to 4.8, respectively, at 37 °C. This shift in the CEST peak correlates with the protonation of the unbound 2-amino-6-picolyl pendents, as suggested by UV-vis and 1H NMR spectroscopy studies at different pH values. Phantom imaging demonstrates the challenges and feasibility of using the [Fe(TAPC)]2+ agent on a low-field MRI scanner. The [Fe(TAPC)]2+ complex is the first transition-metal-based paraCEST agent that produces a pH-induced CEST frequency change toward the development of probes for concentration-independent imaging of pH.

FUSED HETEROCYCLIC DERIVATIVES, THEIR PREPARATION METHODS THEREOF AND MEDICAL USES THEREOF

The present invention relates to fused heterocyclic derivatives, processes for their preparation and their use in medicine. Specifically, the present invention relates to a novel derivative represented by the formula (I′), or its pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the derivative or its pharmaceutically acceptable salt thereof, and the method for preparing the derivative and its pharmaceutically acceptable salt thereof. The present invention also relates to the use of the derivative and its pharmaceutically acceptable salt thereof, or a pharmaceutical composition containing the derivative and its pharmaceutically acceptable salt thereof in the preparation of medicines, in particularly as IDO inhibitor medicines, for treating and/or preventing cancers. Wherein each substituent of the formula (I′) is the same as defined in the specification.

The identification of AF38469: An orally bioavailable inhibitor of the VPS10P family sorting receptor Sortilin

The identification of the novel, selective, orally bioavailable Sortilin inhibitor AF38469 is described. Structure-activity relationships and syntheses are reported, along with an X-ray crystal structure of the sortilin-AF38469 protein-inhibitor complex.

Novel pyrrolyl 2-aminopyridines as potent and selective human β-secretase (BACE1) inhibitors

The proteolytic enzyme β-secretase (BACE1) plays a central role in the synthesis of the pathogenic β-amyloid in Alzheimer's disease. Recently, we reported small molecule acylguanidines as potent BACE1 inhibitors. However, many of these acylguanidines have a high polar surface area (e.g. as measured by the topological polar surface area or TPSA), which is unfavorable for crossing the blood-brain barrier. Herein, we describe the identification of the 2-aminopyridine moiety as a bioisosteric replacement of the acylguanidine moiety, which resulted in inhibitors with lower TPSA values and superior brain penetration. X-ray crystallographic studies indicated that the 2-aminopyridine moiety interacts directly with the catalytic aspartic acids Asp32 and Asp228 via a hydrogen-bonding network.

Synthesis, characterization, photoinduced isomerization, and spectroscopic properties of vinyl-1,8-naphthyridine derivatives and their copper(I) complexes

A series of 1,8-naphthyridine derivatives containing vinyl, 2-(2-acetylamino-pyridine-6-ethylene)-4-methyl-7-acetylamino-1,8-naphthyridine (L1), 2-(2-acetylamino-pyridine-6-ethylene)-1,8-naphthyridine (L 2), 2-(2-acetylamino-pyridinyl-6-ethylene)-4-methyl-7-hydroxyl-1,8- naphthyridine (L3), 2-(2-diacetylamino-pyridinyl-3-ethylene)-7- diacetylamino-1,8-naphthyridine (L4), and 7-(2-diacetylamino- pyridinyl-3-ethylene)-4′-acetyl-pyrrolo[1′,5′-a]-1, 8-naphthyridine (L5), as well as complexes [CuL1(PCy 3)](BF4)2 (1) (PCy3 = tricyclohexylphosphine), [Cu2L1(PPh3) 4](BF4)2 (2) (PPh3 = triphenylphosphine), [Cu2L1(dppm)](BF4) 2 (3) (dppm = bis(diphenylphosphino)methane), and [Cu 2(L1)(dcpm)][BF4]2 (4) (dcpm = bis(dicyclohexylphosphino)methane, were synthesized. All these compounds, except for L1 and L2, were characterized by single crystal X-ray diffraction analysis, and a comprehensive study of their spectroscopic properties involving experimental theoretical studies is presented. We found an intramolecular 1,3-hydrogen transfer during the formation of L3 and L4, which in the case of the latter plays an important role in the 1,5-dipolar cyclization of L5. The spectral changes that originate from an intramolecular charge transfer (ICT) in the form of a πpy→π*napy transition can be tuned through acid/base-controlled switching for L1-L3. A photoinduced isomerization for L1-L3, 1, and 2 having flexible structures was observed under 365 nm light irradiation. Quantum chemical calculations revealed that the dinuclear complexes with structural asymmetry exhibit different metal-to-ligand charge-transfer transitions.

Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of β-secretase

Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme β-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 μM) and 6c (IC50 = 24 μM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM).

SUBSTITUTED AMINOPYRIDINES AND USES THEREOF

This invention relates to novel compounds having the structural formula (I) and to their pharmaceutically acceptable salt, compositions and methods of use. These novel compounds provide a treatment or prophylaxis of cognitive impairment, Alzheimer Disease, neurodegeneration and dementia.

New anti-inflammatory N-pyridinyl(alkyl)phthalimides acting as tumour necrosis factor-α production inhibitors

This paper describes the synthesis of N-pyridinyl(alkyl)phthalimides related to N-phenyl-4,5,6,7-tetrafluorophthalimides known to be inhibitors of tumour necrosis factor-α (TNFα) production. Pharmacomodulation at the phthalimidic nitrogen led to the selection of two pharmacophoric fragments (2,4-lutidinyl and β-picolyl), allowing significant inhibition of TNFα production (compounds 12 and 17). Variation of the substituents linked to the homocycle of their phthalimide scaffold indicated that high (TNFα production) inhibitory potency could be achieved, notably by 5-fluoro, 4- or 5-nitro, 5-amino and especially tetrafluoro substitution. The most active compound, N-(pyridin-3-ylmethyl)-4,5,6,7-tetrafluorophthalimide (32) (84% inhibition at 10 μM), also produced an anti-oedematous effect in the PMA-induced mouse-ear swelling test. Although less active than dexamethasone, it exerted a marked reduction in ear thickness after oral administration (63% vs. 85% for dexamethasone at 0.2 mM kg-1) and remained efficient after topical application (46% vs. 96% for the dexamethasone). It also induced potent inhibition in the rat carrageenan foot oedema test with an ID50 (0.14 μM kg-1) comparable with that of N-(2,6-diisopropylphenyl)phthalimide (4) (0.15 μM kg-1).

Vitronectin receptor antagonists

Compounds of formula (I) are disclosed which are vitronectin receptor antagonists useful in the treatment of osteoporosis.