69716-28-5

Usage

Synthesis Reference(s)

Synthetic Communications, 18, p. 1427, 1988 DOI: 10.1080/00397918808078813

Upstream product

• 1772-01-6 2-pyridylamidoxime 
• 1772-01-6 (Z)-N'-hydroxy-pyridine-2-carboxamidine 
• 100-70-9 2-Cyanopyridine 
• 1193-96-0 (E)-pyridin-2-aldoxime 
• 1121-60-4 pyridine-2-carbaldehyde 
• 873-69-8 2-pyridinealdoxime 

Downstream Products

• 146561-41-3 (hydroxyimino)-2-pyridylacetonitrile 
• 107535-16-0 benzyl-2-pyridylhydroxyiminomethyl thioether 
• 1236144-59-4 tert-butyl 1-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate 
• 1236144-85-6 tert-butyl 1-(4-(5-(4-propyl-3-(pyridin-2-yl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylate 
• 1236144-62-9 5-(4-iodo-3-(pyridin-2-yl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazole 
• 1236144-61-8 5-(4-bromo-3-(pyridin-2-yl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazole 
• 161531-30-2 5-Amino-3-phenyl-5-pyridin-2-yl-pentane-1,3-diol 
• 161531-29-9 5-(2-hydroxyethyl)-5-phenyl-3-(pyrid-2-yl)-Δ²-isoxazoline 
• 1236144-60-7 5-(3-(pyridin-2-yl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazole 
• 1236144-63-0 5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-3-p-tolyl-1,2,4-oxadiazole 
• 1236144-64-1 3-(4-(bromomethyl)phenyl)-5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole 
• 1236144-37-8 1-(4-(5-(3-(pyridin-2-yl)-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid 

Relevant academic research and scientific papers

CBP/CATENIN SIGNALING PATHWAY INHIBITORS AND USES THEREOF

Provided are compounds of formula (Ia), (Ib) and (IIa), and pharmaceutically acceptable salts thereof. Additionally provided are compositions and pharmaceutical compositions comprising the compounds, therapeutic methods using same for modulating (e.g., inhibiting) CREB binding protein (CBP)/β-catenin mediated signaling in treating a condition, disease or disorder (e.g., fibrosis, cancer, neurological conditions, metabolic disorders (e.g., diabetes, etc.), and skin conditions (dermatitis, psoriasis, scarring, alopecia, etc.) mediated by aberrant CBP/β -catenin signaling, and cosmetic methods for treating skin conditions (e.g., aging, etc.). Additionally provided are methods for enhancing vaccine efficacy using the compounds and compositions. Further provided are methods for efficiently synthesizing a clinical grade drug, comprising use, in a penultimate, or last reaction step under GMP conditions, of an intermediate 2-propynyl-compound to form a clinical grade isoxazole derivative (e.g., via 3+2 cycloaddition).

SUBSTITUTED AMINOTHIAZOLES AS DGKZETA INHIBITORS FOR IMMUNE ACTIVATION

The present invention covers aminothiazole compounds of general formula (I) : in which R1, R2, R3 and R4 are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing sa

ADENOSINE ANALOGS FOR THE TREATMENT OF DISEASE

The disclosure provides adenosine analogs for the treatment of disease such as pain and inflammatory conditions.

1,3-Dipolar Cycloaddition, HPLC Enantioseparation, and Docking Studies of Saccharin/Isoxazole and Saccharin/Isoxazoline Derivatives as Selective Carbonic Anhydrase IX and XII Inhibitors

Two series of saccharin/isoxazole and saccharin/isoxazoline hybrids were synthesized by 1,3-dipolar cycloaddition. The new compounds showed to be endowed with potent and selective inhibitory activity against the cancer-related human carbonic anhydrase (hCA) IX and XII isoforms in the nanomolar range, while no affinity was encountered for off-targets, such as hCA I and II. Successive enantioseparation on a milligram scale of the most representative compounds led to the discovery that (S)-isomers were more potent than their corresponding (R)-enantiomers. Lastly, molecular modeling studies were conducted to define those structural requirements that were responsible for the discrimination among selected human isoforms of carbonic anhydrases. Two nanomolar hCA IX and XII inhibitors were also screened for their selective toxicity against non tumoral primary cells (fibroblasts) and against a breast adenocarcinoma cell line (MCF7) in hypoxic environment. The efficacious combination of these compounds with doxorubicin on MCF7 cells was demonstrated after 72 h of treatment.

Stereospecific 1,4-Metallate Shift Enables Stereoconvergent Synthesis of Ketoximes

Reported herein is a stereospecific 1,4-metallate rearrangement for single-geometry ketoxime synthesis from oxime chlorides and arylboronic acids. This strategy exhibits broad substrate scope with excellent stereoselectivity under mild reaction conditions. In comparison with the conventional approaches, each configuration of unsymmetric diaryl oximes, as well as the thermodynamically less stable Z isomer of aryl alkyl ketoximes can be selectively and exclusively obtained. The reactivities of unsymmetric diaryl oximes and the Z isomer of aryl alkyl oximes, a class of underexplored molecules, enables efficient access to the corresponding isoquinolines, isoquinoline N-oxides, and amides having a single configuration.

Synthesis of Triazolo- and Oxadiazolopiperazines by Gold(I)-Catalyzed Domino Cyclization: Application to the Design of a Mitogen Activated Protein (MAP) Kinase Inhibitor

An efficient method for the synthesis of [1,2,4]triazolo[4,3-a]piperazine derivatives was established based on a gold(I)-catalyzed domino cyclization of an amidrazone substrate with a terminal alkyne. The amidoxime congeners were converted into [1,2,4]oxadiazolo[4,5-a]piperazine derivatives in the presence of a gold catalyst. The oxadiazolopiperazine is a promising scaffold for the design of novel inhibitors against p38 mitogen activated protein kinase (MAP kinase).

CALPAIN MODULATORS AND THERAPEUTIC USES THEREOF

Disclosed herein are small molecule calpain modulator compositions, pharmaceutical compositions, the use and preparation thereof.

Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions

[3+2] reactions play a key role in constructing various pharmaceutical moleculars. In this study, using Mn(OAc)3 mediated and 1,3-dipolar [3+2] cyclization reactions, 38 novel dihydrofuran and dihydroisoxazole analogues of isoCA-4 were synthesized as inhibitors of tubulin polymerization. Among them, compound 6g was found to be the most potent cytotoxic agents against PC-3 cells with IC50 value of 0.47 μM, and compound 5p exhibted highest activity on HeLa cells with IC50 vaule of 2.32 μM. Tubulin polymerization assay revealed that 6g was a dose-dependent and effective inhibitor of tubulin assembly. Immunohistochemistry studies and cell cycle distribution analysis indicated that 6g severely disrupted microtubule network and significantly arrested most cells in the G2/M phase of the cell cycle in PC-3 cells. In addition, molecular docking studies showed that two chiral isomers of 6g can bind efficiently and similarly at colchicine binding site of tubulin.

Water-Assisted Nitrile Oxide Cycloadditions: Synthesis of Isoxazoles and Stereoselective Syntheses of Isoxazolines and 1,2,4-Oxadiazoles

Conventional methods generate nitrile oxides from oxime halides in organic solvents under basic conditions. However, the present work revealed that water-assisted generation of nitrile oxides proceeds under mild acidic conditions (pH 4-5). Cycloadditions of nitrile oxides with alkynes and alkenes easily occurred in water without using catalysts, thus yielding isoxazoles and isoxazolines, respectively, with excellent stereoselectivity toward five- and six-membered cyclic alkenes. A double stereoselective cycloaddition of two units of a nitrile oxide with cyclohexene was also achieved, thus yielding 1,2,4-oxadiazole derivatives having a unique hybrid isoxazoline-oxadiazole skeleton. Enantiomerically pure isoxazolines were prepared from monoterpenes with a ring strain. In one case, the isoxazoline with a butterfly-like structure was simply prepared, and it might be used as a ligand in asymmetric catalysis.

THERAPEUTIC COMPOUNDS AND USES THEREOF

The present invention relates to compounds formula (I): and to salts thereof, wherein R1-R4 and A have any of the values defined in the specification, and compositions and uses thereof. The compounds are useful as inhibitors of histone demethylases, such as KDM5. Also included are pharmaceutically acceptable compositions comprising the compounds of the present invention and methods of using said compositions in the treatment of various disorders.