Anuradha Gupta

Discovery of BMS-986449: A Potent, Selective Degrader of the Transcription Factors IKZF2 (Helios) and IKZF4 (Eos) to Target Regulatory T Cells in Solid Tumors

Emily C. Cherney, Satheesh K. Nair, Suresh Babu Viswa Krishna Penmetsa, Bharat Shimpukade et autres

Within the tumor microenvironment (TME), regulatory T (Treg) cells promote an immunosuppressive state with limited tumor antigen presentation and antitumor effector T (Teff) cell responses, which can drive resistance to cancer immunotherapies. IKZF2 (Helios) is a transcription factor essential for stabilizing the …

de, us, gb, be, in (code pays fourni par la source)

Discovery of BMS-159, an Orally Active Imidazotriazine Pan-CK2 Inhibitor for the Treatment of Cancer

Christine M. Tarby, Amy C. Hart, Honghe Wan, Liqi He et autres

Casein kinase 2 (CK2), comprising the catalytic subunits CK2α and CK2α′, is a highly conserved and constitutively active serine/threonine kinase that is implicated in oncogenic signaling and tumor maintenance, making it an attractive therapeutic target. We report a medicinal chemistry campaign that …

de, se, in (code pays fourni par la source)

Pd-Catalyzed Buchwald–Hartwig Coupling of Imidazo[1,2-b]pyridazine with Aryl/Hetero Aryl Amines for the Synthesis of Functionalized Pyridazines

Roshan Y. Nimje, Santhosh Rao, Chiradeep Panja, Ramakrishna Panchakharla et autres

Abstract This work describes a practical method for coupling chloropyridazines and aryl/hetero aryl amines to get substituted aryl/hetroarylaminopyridazines. The newly developed condition tolerates a wide range of functional groups, including various heterocycles, electron-withdrawing/donating groups, and sensitive functional groups. This approach offers a …

in, de, se, jp (code pays fourni par la source)

Desymmetrization of meso -Anhydride Enabled Enantioselective Synthesis of (−)-7-(Bromomethylene)-3-amidobicyclo[2.2.1]heptane-2-carboxamide, a Scaffold for Divergent Drug Discovery Synthesis

Jianqing Li, Subramaniam Krishnananthan, Daniel Smith, Chetan Padmakar Darne et autres

An enantioselective synthesis (>99% ee) of (−)-(1 R, 2 S, 3 R, 4 R,Z )-7-(bromomethylene)- N -(4-fluoro-3-(trifluoromethyl)phenyl)-3-(2,2,2-trifluoroacetamido)bicyclo[2.2.1]heptane-2-carboxamide ((−)- 1 ), a scaffold for divergent drug discovery synthesis, has been developed. The synthesis employed dimethyl(phenyl)silyl moiety as a “masked” hydroxy group and started …

de, us, gb, be, ie, ch, in (code pays fourni par la source)

Beyond Bioisosteres: Impact of Replacing a Benzene Ring with sp3-Rich Three-Dimensional Saturated Bridged Bicyclic Match Pairs on Biotransformation, Metabolic Stability, and Other ADME Profiles

Shruti Surendran, Sivashankaran Raju, Joyson Nandha, Himangshu Bhowmik et autres

Abstract The increasing adoption of 3D sp3-hybridized bridged bicyclic moieties as saturated bioisosteres of benzene rings signifies a compelling evolution in modern medicinal chemistry, facilitated by recent synthetic advancements. Inspired by this, we evaluated the metabolic stability and other ADME profiles of …

in, de, gb, be (code pays fourni par la source)

Development of a Multigram Preparation of Optically Pure (−)-7-(Bromomethylene)-3-amidobicyclo[2.2.1]heptane-2-carboxamide BMT-395137, a Versatile Scaffold for Divergent Drug Discovery Synthesis

Jianqing Li, Daniel Smith, Lyndon A. M. Cornelius, Subramaniam Krishnananthan et autres

This paper describes the development of a synthetic route for the multigram synthesis of (−)-(1 R,2 S,3 R,4 R, Z )-7-(bromomethylene)- N -(4-fluoro-3-(trifluoromethyl)phenyl)-3-(2,2,2-trifluoroacetamido)bicyclo[2.2.1]heptane-2-carboxamide ((−) -14, BMT-395173), a versatile scaffold for divergent drug discovery synthesis. This new process begins with readily available commercial …

de, us, ch, in (code pays fourni par la source)

Discovery and Characterization of a First-in-Class LIV1-TLR7/8 Immunomodulatory Conjugate with Robust Myeloid Activation and Antitumor Activity

Sayumi Yamazoe, Yam B. Poudel, Emanuela Sega, Anandaroop Mukhopadhyay et autres

Herein, we describe the discovery of a novel immunostimulatory drug conjugate (IMC) that employs TLR7/8 agonists conjugated to a tumor-targeting LIV1 antibody. Targeting TLR7/8 agonists to LIV1-expressing tumors enables localized delivery, thereby minimizing systemic toxicity while promoting inflammation and T cell recruitment …

us, de, ch, in (code pays fourni par la source)

Efficient and Scalable Diastereoselective Synthesis of ((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methanol Hydrochloride

Rulin Zhao, Zhenqiu Hong, Bei Wang, Daniel Smith et autres

An efficient large-scale synthesis of 2a ·HCl, a key fragment to several KRAS inhibitors, is described. Optimization to a previously reported racemic route by Merck includes the development of a catalytic exocyclic olefin oxidation using RuCl 3 /NaIO 4, followed by a …

de, in (code pays fourni par la source)

Shapeshifting Gabriel Amine Synthesis with Iodo-BCPs

Manivel Pitchai, Nanjundaswamy K.C., Ulaganathan Sankar, Mohammad Javeed et autres

The Gabriel amine synthesis is a textbook method for the preparation of primary amines from alkyl halides. In this work, we demonstrate a Gabriel amine synthesis with iodo-bicyclopentanes to make aminomethyl bicyclobutanes. DFT studies support the concerted rearrangement of a bicyclo[1.1.1]pentyl to …

in, us, fr, de (code pays fourni par la source)

Development of a Scalable Stereoselective Synthesis of Selected Potent ROMK Inhibitors

Premsai Rai Neithnadka, Mohamed M. Abdulla, Chiradeep Panja, Arunachalam Arumugam et autres

An efficient and scalable synthesis of two small-molecule renal outer medullary potassium (ROMK) inhibitors 1 and 2 was developed from readily available raw material. The alternative approach includes a newly developed asymmetric reduction of the keto intermediate to access compound 1 and …

in, de, us, sg (code pays fourni par la source)

Synthesis of Functionalized 3‐Azabicyclo[3.2.0]Heptanes via Visible‐Light Energy‐Transfer Catalysis

Manivel Pitchai, Mahammed Kaspady, Madhavan Kannan, Arunkumar Akunuri et autres

Abstract Functionalized cyclobutanes are three‐dimensional scaffolds widely found in natural products and bioactive molecules. Herein, we report a visible‐light‐induced intermolecular [2+2] cycloaddition reaction of a diverse array of alkenes with N ‐substituted maleimides to access functionalized azabicyclo[3.2.0]heptanes. The reaction showed broad substrate …

in, us (code pays fourni par la source)

A concise, stereoselective and scalable synthesis of optically pure (3R,4R)-1-benzyl- and (3R,4R)-1-Boc-3-methyl-4-aminopiperidines

Sunit Hazra, Ankit Kangune, Govind Goroba Pawar, Kumar B. Pabbisetty et autres

in, de, us, se (code pays fourni par la source)