36132-96-4

Upstream product

• 36132-95-3 (2-hydroxymethyl-5-methoxy-phenyl)-methanol 
• 4685-47-6 3,4-dimethylanisole 
• 95-65-8 3,4-Dimethylphenol 
• 22479-95-4 dimethyl 4-hydroxyphthalate 
• 22895-19-8 dimethyl 4-methoxyphtalate 
• 1885-13-8 4-methoxyphthalic acid 

Downstream Products

• 36132-97-5 4-methoxy-1,2-benzenediacetonitrile 
• 400762-88-1 1,2-bis(azidomethyl)-4-methoxybenzene 
• 1025424-06-9 5-methoxy-2-[(4-methylphenyl)sulfonyl]isoindoline 
• 127168-89-2 N-benzylisoindolin-5-yl methyl ether 

Relevant academic research and scientific papers

1-(dibromomethyl)-4-methoxy-2-methylbenzene

The title compound, C9H10Br2O, is a major product of the radical bromination of 4-methoxy-1,2-dimethylbenzene. Each Br atom is involved in a close contact with the O atom of a neighbouring molecule, forming a geometry that is suggestive of weak intermolecular O→Br charge-transfer interactions.

Syntheses of new hydroxy-[3.3]orthocyclophanes as models for the galactose oxidase Tyr-Cys cofactor

The syntheses of 3,4-benzo-8,9-(3′-hydroxybenzo)bicyclo[4,4,1]undeca-3,8-dien-11-one, 3,4-benzo-8,9-(3′-hydroxy-4′-methylsulfanylbenzo)bicyclo[4,4,1] undeca-3,8-dien-11-one and their ethylene acetals have been achieved. Crystallographic, UV/Vis and NMR data show that the two ketones adopt boat/chair conformations that are fluxional in solution, while the acetals exhibit chair/chair conformations with layered benzo rings. Comparison of the oxidation potentials of the four compounds suggests that an ortho-methylsulfanyl substituent and a π-π interaction both thermodynamically stabilise the phenoxonium radical species derived from these compounds, by approximately equal amounts.

Structure-Activity Relationships of Benzamides and Isoindolines Designed as SARS-CoV Protease Inhibitors Effective against SARS-CoV-2

Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide (2 b), which is known to bind into the S3 and S4 pockets of the SARS-CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PLpro are valuable starting points for the development of new pan-coronaviral inhibitors.

A Spiroalkylation Method for the Stereoselective Construction of α-Quaternary Carbons and Its Application to the Total Synthesis of (R)-Puraquinonic Acid

Cyclic α-quaternary carbon stereocenters were prepared from biselectrophillic substrates and an easily prepared chiral bicyclic sulfonyl lactam. This was achieved in two steps by spiroalkylation, employing biphasic reaction conditions with a phase-transfer catalyst, followed by reduction and alkylation with a series of alkyl halide electrophiles. The products of this method were isolated in good yields with with high levels of diastereoselectivity. This methodology was employed in the enantioselective total synthesis of (R)-puraquinonic acid (1) for a late-stage installation of the α-quaternary carbon stereocenter. This enabled the shortest synthesis of 1 to date, an eight-pot sequence providing an overall yield of 14%.

SPIRO-COMPOUNDS AS S1P MODULATORS

The invention relates to heterocyclic compounds of formula (I) as SIP modulators, pharmaceutical compositions comprising such compounds, and uses thereof in the treatment or alleviation of diseases or disorders mediated by an SIP receptor.

Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase

Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancer, supported by considerable favorable preclinical and clinical activities over the past several years and culminating in the recent FDA approval of the ALK inhib

ISOINDOLINE COMPOUNDS FOR THE TREATMENT OF SPINAL MUSCULAR ATROPHY AND OTHER USES

Disclosed is a compound of Formula (I) in which W and R1-R6 are defined herein. Also disclosed is a method of treating spinal muscular atrophy, as well as methods of using such compounds to increase SMN expression, increase EAAT2 expression, or increase the expression of a nucleic acid that encodes a translational stop codon introduced directly or indirectly by mutation or frameshift.

SAR studies of capsazepinoid bronchodilators. Part 1: The importance of the catechol moiety and aspects of the B-ring structure

Capsazepine as well as its derivatives and analogues are general inhibitors of constriction of human small airways. From a systematic variation of the capsazepine structure, divided into four regions, SARs were established. This part concerns the catechol moiety of the A-ring as well as the 2,3,4,5-tetrahydro-1H-2-azepine moiety (the B-ring) of capsazepine. It is revealed that a conformational constrain (as a fused ring) is important and that compounds with a six-membered B-ring (as a 1,2,3,4-tetrahydroisoquinoline) in general are more potent than the corresponding isoindoline, 2,3,4,5-tetrahydro-1H-2-benzazepine and 2,3,4,5-tetrahydro-1H-3-benzazepine derivatives.

Design, synthesis, and evaluation of fused heterocyclic analogs of SCH 58261 as adenosine A2A receptor antagonists

SCH 58261 is a reported adenosine A2A receptor antagonist which is active in rat in vivo models of Parkinson's Disease upon ip administration. However, it has poor selectivity versus the A1 receptor and does not demonstrate oral activity. Quinoline analogs have improved upon the selectivity and pharmacokinetics of SCH 58261, but were difficult to handle due to poor aqueous solubility. We report the design and synthesis of fused heterocyclic analogs of SCH 58261 with aqueous solubility as well as improved A2A receptor binding selectivity and pharmacokinetic properties. In particular, the tetrahydronaphthyridine 4s has excellent A2A receptor in vitro binding affinity and selectivity, is active orally in a rat in vivo model of Parkinson's Disease, and has aqueous solubility of 100 μM at physiological pH.

Formation of 4,5,6,7-tetrahydroisoindoles by palladium-catalyzed hydride reduction

(Chemical Equation Presented) Substituted 1,3-dihydro-2H-isoindoles (2, isoindolines) were prepared and subjected to palladium-catalyzed formate reduction. Alkyl isoindolines were reduced to 4,5,6,7-tetrahydro-2H-isoindoles (1). Only partial reduction was observed for 5-methoxyisoindoline, and 4-methoxy-, 5-carbomethoxy-, amino-, and amidoisoindolines were inert to the reaction. Halogen-substituted isoindolines were dehalogenated and reduced to 4,5,6,7-tetrahydro-2H-isoindoles. Isoindole 24 was also reduced to a mixture of an isoindoline and a 4,5,6,7-tetrahydro-2H-isoindole. In contrast, 2,3-dihydro-1H-indoles 21 underwent dehydrogenation to give thermodynamically stable indoles. Theoretical calculations show the significant difference in aromaticity between isoindoles and indoles, corresponding to the observed differences in reactivities. Tetrahydro-2H-isoindoles 1 were oxidized to 4,5,6,7-tetrahydroisoindole-1,3-diones in the presence of NBS and air.