16507-06-5

Upstream product

• 623-43-8 crotonic acid methyl ester 
• 148116-22-7 1,5-Diazabicyclo[5.4.0]undec-5-ene 
• 75-52-5 nitromethane 
• 623-43-8 methyl crotonate 

Downstream Products

• 107954-49-4 2,3-dihydro-2-methyl-3-(phenylmethylene)pyrrolo<2,1-b>quinazoline-9(1H)-one 

Relevant academic research and scientific papers

Synthesis and biological evaluation of 2-aryliminopyrrolidines as selective ligands for I1 imidazoline receptors: Discovery of new sympatho-inhibitory hypotensive agents with potential beneficial effects in metabolic syndrome

New 2-aryliminopyrrolidines (1-18) were synthesized and tested for their binding properties on I1 imidazoline receptors vs α2-adrenergic receptors and their blood pressure effects after both systemic and intracerebral administrations

Synthetic Studies of the Rubellin Natural Products: Development of a Stereoselective Strategy and Total Synthesis of (+)-Rubellin C

This manuscript describes our studies of the class of natural products known as the rubellins, culminating in the total synthesis of (+)-rubellin C. These anthraquinone-based natural products contain a variety of stereochemical and architectural motifs, including a 6-5-6-fused ring system, 5 stereogenic centers, and a central quaternary center. Herein, we report our development of a strategy to target the stereochemically dense core and anthraquinone nucleus, including approaches such as a bifunctional allylboron and vinyl triflate reagent, an anthraquinone benzylic metalation strategy, and a late-stage anthraquinone introduction strategy. Our studies culminate in a successful route to highly functionalized anthraquinone-based natural product scaffolds and a stereoselective total synthesis of (+)-rubellin C. These strategies and outcomes will aid in synthetic planning toward anthraquinone-based natural products of high interest.

Effect of the Substituent and Amino Group Position on the Lipase-Catalyzed Resolution of γ-Amino Esters: A Molecular Docking Study Shedding Light on Candida antarctica lipase B Enantioselectivity

The kinetic resolution of N-tert-butoxycarbonyl γ-amino methyl esters bearing different stereocenters at alpha (γ2), beta (γ3), or gamma (γ4) positions was carried out by enantioselective hydrolysis with Candida antarctica lipase B (CaLB) in 2-methyl-2-butanol solvent. The results show that the process is significantly less enantioselective for the γ2-amino methyl ester (E=2.5), the γ3-amino methyl ester (E=7.6), and the γ4-amino methyl ester (E=8.3) when compared with the kinetic resolution of analogous N-protected β3-amino esters (E>80). Based on these results, molecular docking studies were carried out, through which particular regions in the CaLB catalytic cavity were analyzed. The steric exclusion region composed of Ile189 and Val190 residues, together with the amino bonding region that induces a hydrogen bond with the Asp134 residue, appear to be responsible for the high selectivity in the resolution of carboxylic acid derivatives with beta stereocenters. This interaction is well preserved for β-amino esters as substrates. By contrast, γ-amino esters exhibit greater conformational diversity, so the effectiveness of the interaction is reduced, which apparently is responsible for the loss of enantioselectivity in the resolution process.

APOPTOSIS SIGNAL-REGULATING KINASE INHIBITORS AND USES THEREOF

Described herein are ASK1 inhibitors and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of blood disease, autoimmune disorders, pulmonary disorders, hypertension, inflammatory diseases, fibrotic diseases, diabetes, diabetic nephropathy, renal diseases, respiratory diseases, cardiovascular diseases, acute lung injuries, acute or chronic liver diseases, and neurodegenerative diseases.

Bcl-2 INHIBITORS

Disclosed herein is a compound of Formula (I) for inhibiting Bcl-2 and treating disease associated with undesirable bcl-2 activity (Bcl-2 related diseases), a method of using the compounds disclosed herein for treating dysregulated apoptotic diseases including cancers and treating autoimmune disease, and a pharmaceutical composition comprising the same.

LP99: Discovery and synthesis of the first selective BRD7/9 bromodomain inhibitor

The bromodomain-containing proteins BRD9 and BRD7 are part of the human SWI/SNF chromatin-remodeling complexes BAF and PBAF. To date, no selective inhibitor for BRD7/9 has been reported despite its potential value as a biological tool or as a lead for future therapeutics. The quinolone-fused lactam LP99 is now reported as the first potent and selective inhibitor of the BRD7 and BRD9 bromodomains. Development of LP99 from a fragment hit was expedited through balancing structure-based inhibitor design and biophysical characterization against tractable chemical synthesis: Complexity-building nitro-Mannich/lactamization cascade processes allowed for early structure-activity relationship studies whereas an enantioselective organocatalytic nitro-Mannich reaction enabled the synthesis of the lead scaffold in enantioenriched form and on scale. This epigenetic probe was shown to inhibit the association of BRD7 and BRD9 to acetylated histones invitro and in cells. Moreover, LP99 was used to demonstrate that BRD7/9 plays a role in regulating pro-inflammatory cytokine secretion.

Synthesis of functionalized γ-lactone via Sakurai exo -cyclization/rearrangement of 3,3-bis(silyl) enol ester with a tethered acetal

An efficient synthesis of functionalized γ-lactones has been developed involving Sakurai exo-cyclization/rearrangement of 3,3-bis(silyl) enol esters with a tethered acetal. While the steric and electronic effects of geminal bis(silane) favor the desired Sakurai pathway, the methoxy species formed in the deprotection step also facilitates both cyclization and rearrangement. The synthetic value of this approach has been demonstrated by efficiently transforming the E-vinylsilane into enyne and the γ-lactone moiety into multisubstituted THF.

NOVEL AMINO-PYRROLINE DERIVATIVES, AND USE THEREOF IN THE PREVENTION AND/OR TREATMENT OF METABOLIC SYNDROME

Novel amino-pyrrolinic derivatives, their pharmacologically acceptable salts and use thereof in the prevention and/or treatment of metabolic syndrome.

Synthesis of γ-nitro aliphatic methyl esters via michael additions promoted by microwave irradiation

A simple and efficient protocol has been developed for the direct synthesis of γ-nitrobutyric acid methyl esters under microwave irradiation. This methodology reduces reaction times from days to minutes, compared to conventional conditions. Additionally, these conditions increased yields and provided cleaner reactions.

DIPEPTIDYL PEPTIDASE-IV INHIBITING COMPOUNDS, METHODS OF PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE AGENT

The present invention relates to novel compounds exhibiting good inhibitory activity versus Dipeptidyl Peptidase-IV(DPP-IV), methods of preparing the same and pharmaceutical compositions containing the same as an active agent.