23754-46-3

Upstream product

• 79-37-8 oxalyl dichloride 
• 1679-64-7 Monomethyl terephthalate 
• 1257841-78-3 2-(4-methoxycarbonylbenzoyloxy)-1-methylpyridinium triflate 
• 74-89-5 methylamine 
• 593-51-1 methylamine hydrochloride 
• 7377-26-6 4-Methoxycarbonylbenzoyl chloride 
• 619-42-1 4-methoxycarbonylphenyl bromide 
• 335344-28-0 N‐methoxymethyl‐N‐methylcarbamoyl(trimethyl)silane 

Downstream Products

• 1315257-14-7 methyl 2-methyl-1-oxo-3,4-diphenyl-1,2-dihydroisoquinoline-6-carboxylate 
• 1423058-84-7 C₉H₁₀N₂O₃ 
• 349491-81-2 N-benzyl-terephthalamic acid methyl ester 
• 23754-45-2 4-(Methylaminocarbonyl)benzoic acid 

Relevant academic research and scientific papers

Ring size changes in the development of class I HDAC inhibitors

Five pathways involving different ring structures led to generation of fourteen thienylbenzamides (7–20) which display the structure-activity relationships of class I HDAC inhibitors. All the synthesised compounds inhibit HDAC1 and HDAC2 selectively over other isoforms and many inhibit DLD1 and HCT116 cells more effectively than a parent compound. Compounds 8 and 16 inhibit HCT116 cells by activation of the apoptosis pathway.

Iridium-catalyzed, ligand-controlled directed alkynylation and alkenylation of arenes with terminal alkynes

We report iridium-catalyzed C-C formation between benzamides and terminal alkynes. With the choice of a suitable ligand, a C-H alkynylation or alkenylation product could be obtained selectively. The directed C-H alkynylation proceeded without the need for an external oxidant, while the directed C-H alkenylation likely involves an unusual vinylidene mechanism. This divergent reactivity provides access to both alkynylation and alkenylation products from the same set of starting materials.

KCNT1 INHIBITORS AND METHODS OF USE

The present invention is directed to, in part, compounds and compositions useful for preventing and/or treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene (e.g., KCNT1). Methods of treating a neurological disease or disorder, a disease or condition relating to excessive neuronal excitability, and/or a gain-of-function mutation in a gene such as KCNT1 are also provided herein.

Nickel-catalyzed aminocarbonylation of aryl halides with carbamoylsilanes: efficient synthesis of secondary (primary) aromatic amides

A nickel-catalyzed aminocarbonylation of aryl halides using carbamoylsilane as an amide source leading to corresponding secondary or primary aromatic amides has been developed, in which the methoxymethyl and benzyl were used as amino protecting group. The protocol tolerates a broad range of aryl halides bearing different functional groups to afford good yields of aryl amides under mild reaction conditions. The types and the relative positions of substituents on the aryl ring make a notable impact on the coupling efficiency. The plausible mechanism of nickel-catalyzed aminocarbonylation has been suggested.

Novel Human Aminopeptidase N Inhibitors: Discovery and Optimization of Subsite Binding Interactions

Aminopeptidase N (APN/CD13) is a zinc-dependent M1 aminopeptidase that contributes to cancer progression by promoting angiogenesis, metastasis, and tumor invasion. We have previously identified hydroxamic acid-containing analogues that are potent inhibitors of the APN homologue from the malarial parasite Plasmodium falciparum M1 aminopeptidase (PfA-M1). Herein, we describe the rationale that underpins the repurposing of PfA-M1 inhibitors as novel APN inhibitors. A series of novel hydroxamic acid analogues were developed using a structure-based design approach and evaluated their inhibition activities against APN. N-(2-(Hydroxyamino)-2-oxo-1-(3′,4′,5′-trifluoro-[1,1′-biphenyl]-4-yl)ethyl)-4-(methylsulfonamido)benzamide (6ad) proved to be an extremely potent inhibitor of APN activity in vitro, selective against other zinc-dependent enzymes such as matrix metalloproteases, and possessed limited cytotoxicity against Ad293 cells and favorable physicochemical and metabolic stability properties. The combined results indicate that compound 6ad may be a useful lead for the development of anticancer agents.

Rhenium-Catalyzed Phthalide Synthesis from Benzamides and Aldehydes via C-H Bond Activation

The [4 + 1] annulation of benzamides and aldehydes for phthalide synthesis was achieved via rhenium-catalyzed C-H activation, which demonstrates an unprecedented reaction pattern distinct from those of other transition-metal catalyses. The reaction also features readily available starting materials, a wide scope for both electro-rich and electro-deficient substrates, and the elimination of homoannulation byproducts.

Rhodium-Catalyzed Decarbonylative Borylation of Aromatic Thioesters for Facile Diversification of Aromatic Carboxylic Acids

Transformation of aromatic thioesters into arylboronic esters was achieved efficiently using a rhodium catalyst. The broad functional-group tolerance and mild conditions of the method have allowed for the two-step decarboxylative borylation of a wide range of aromatic carboxylic acids, including commercially available drugs.

Potent and selective inhibition of histone deacetylase 6 (HDAC6) does not require a surface-binding motif

Hydroxamic acids were designed, synthesized, and evaluated for their ability to selectively inhibit human histone deacetylase 6 (HDAC6). Several inhibitors, including compound 14 (BRD9757), exhibited excellent potency and selectivity despite the absence of a surface-binding motif. The binding of these highly efficient ligands for HDAC6 is rationalized via structure-activity relationships. These results demonstrate that high selectivity and potent inhibition of HDAC6 can be achieved through careful choice of linker element only.

Re/Mg bimetallic tandem catalysis for [4+2] annulation of benzamides and alkynes via C-H/N-H functionalization

A rhenium-magnesium cocatalyzed [4+2] annulation of benzamides and alkynes via C-H/N-H functionalization is described. The reaction features a divergent and high level of diastereoselectivities, which are readily switchable by subtle tuning of reaction conditions. Thus, a wide range of both cis- and trans-3,4-dihydroisoquinolinones is expediently synthesized in a highly atom-economical manner. Moreover, mechanistic studies unraveled a tandem mode of action between rhenium and magnesium in the catalytic cycles.

Ruthenium-catalyzed oxidative annulation by cleavage of C-H/N-H bonds

Bond activation in action: Unprecedented ruthenium-catalyzed oxidative annulations of alkynes through cleavage of C-H bonds set the stage for an efficient 1(2H)-isoquinolone synthesis with ample scope (see scheme; tAm=tert-amyl). Mechanistic studies provided strong evidence for a rate-limiting C-H bond metalation through carboxylate assistance. Copyright