Article
Pharmacology & Pharmacy
Pawel K. Halik, Przemyslaw Kozminski, Joanna Matalinska, Piotr F. J. Lipinski, Aleksandra Misicka, Ewa Gniazdowska
Summary: Currently, there is a search for promising radiopharmaceuticals that target NK1R-positive tumors based on the structure of small molecular antagonists of the neurokinin-1 receptor. In this study, three novel aprepitant derivatives were synthesized and labeled with Ga-68 and Lu-177. The evaluated radioconjugates showed increased lipophilicity and stability, and demonstrated higher affinity and better binding capacity to the human NK1 receptor compared to the reference Substance P derivative used in glioblastoma therapy.
Article
Pharmacology & Pharmacy
Ruxandra Chira, Jens Fangmeyer, Ioan O. Neaga, Valentin Zaharia, Uwe Karst, Ede Bodoki, Radu Oprean
Summary: This study successfully simulated the oxidative metabolization pattern of netupitant in the liver using an electrochemically driven method. The electrolytic cell mimicked known enzyme-mediated reactions, and the products were identified using high-performance liquid chromatography and mass spectrometry. This electrochemical process not only helps discover unknown metabolites of netupitant but also provides a convenient alternative for further research on therapeutic indications.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2021)
Review
Pharmacology & Pharmacy
Karolina Skorupskaite, Richard A. Anderson
Summary: The essential requirement for kisspeptin and neurokinin B signalling in human reproductive function has sparked interest in the neuroendocrinology of reproduction. The discovery of neurons co-expressing these neuropeptides and regulating hormone secretion provides insight into reproductive processes and symptoms like hot flushes. Antagonists to the neurokinin 3 receptor show promising results in clinical studies for menopausal symptoms and may have potential in other reproductive indications.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Chemistry, Medicinal
Jacopo Tricomi, Luca Landini, Valentina Nieddu, Ugo Cavallaro, Jillian G. Baker, Athanasios Papakyriakou, Barbara Richichi
Summary: Over the past decade, the biomedical applications of molecules that can modulate beta-adrenergic signaling have gained increasing attention, especially in cancer treatment. However, the identification of selective beta-adrenergic receptor (beta-AR) ligands for pharmacological studies and drug development remains a challenging task due to the complexity and specificity requirements of beta-ARs. In this study, we synthesized and evaluated a series of structurally diverse compounds (MC) based on the aryloxy-propanolamine scaffold of SR59230A, aiming to gain insights into the structure-activity relationships of the three beta-AR subtypes. The results provide valuable information on key structural elements and substituents that control the activity and selectivity of these compounds, which could facilitate the development of selective beta-AR drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biology
Ishwar Atre, Naama Mizrahi, Berta Levavi-Sivan
Summary: The study reveals the crucial role of NKB receptors in fish reproduction and identifies the key binding residues and factors involved. Both in vitro and in vivo studies show that these residues are essential for receptor activity.
Article
Multidisciplinary Sciences
Roelof A. Wester, Lisa van Voorthuijsen, Hannah K. Neikes, Jelmer J. Dijkstra, Lieke A. Lamers, Siebren Frolich, Maarten van der Sande, Colin Logie, Rik G. H. Lindeboom, Michiel Vermeulen
Summary: Retinoic acid (RA) signaling pathway plays a crucial role in regulating cellular proliferation and differentiation, with perturbations in this pathway implicated in cancer initiation and progression, particularly in the intestine. The activation of Retinoic Acid Receptor and Retinoid X Receptor enhances the transcription of enterocyte-specific genes, while its inhibition results in reduced expression of genes associated with the absorptive lineage, a conserved effect in a human organoid model for colorectal cancer (CRC) progression. Moreover, decreased expression of RXR target genes correlates with poorer CRC prognosis, suggesting RA signaling as a potential therapeutic target in CRC.
Article
Chemistry, Multidisciplinary
Chao Shan, Liming Cao, Jiasheng Yang, Ruihua Cheng, Xiantong Yao, Chaoming Liang, Maolin Sun, Jinxing Ye
Summary: This study has established a highly diastereoselective continuous flow protocol under mild conditions to obtain various functionalized pyrrolidines with rapid, cost-efficient, and scalable access.
REACTION CHEMISTRY & ENGINEERING
(2022)
Article
Endocrinology & Metabolism
Kimball A. Johnson, Nancy Martin, Rossella E. Nappi, Genevieve Neal-Perry, Marla Shapiro, Petra Stute, Rebecca C. Thurston, Wendy Wolfman, Marci English, Catherine Franklin, Misun Lee, Nanette Santoro
Summary: This study assessed the efficacy and safety of fezolinetant for the treatment of moderate to severe vasomotor symptoms (VMS) associated with menopause. The results showed that fezolinetant 30 mg and 45 mg reduced VMS frequency and severity significantly compared to placebo, and were well tolerated.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Medicine, General & Internal
Guang Liu, Yilan Jin, Ying Jiang, Juan Zhao, Caihong Jiang, Zewei Zhang, Lanzhen Zhao, Hui Li, Feng Chen, Jing Wang, Hui Fan, Zhenhao Li, Yongqiang Jia, Gaowa Jin, Quanfu Li
Summary: The objective of this study was to compare the effectiveness and safety of olanzapine and aprepitant in the treatment of vomiting and nausea induced by multiple-day cisplatin chemotherapy. The results showed that there was no significant difference between the two groups in the primary endpoints, as well as the secondary endpoints. Additionally, there were no significant differences in the first vomiting symptom and the impact on quality of life between the two groups. The main adverse event of olanzapine was drowsiness, while constipation was the main adverse event of aprepitant.
INTERNATIONAL JOURNAL OF CLINICAL PRACTICE
(2022)
Review
Immunology
Patrick Grudzien, Henry Neufeld, Mbasogo Ebe Eyenga, Vadim Gaponenko
Summary: Chemokine G-protein coupled receptors are important drug targets for various diseases, but the development of chemokine receptor antagonists has been slow due to antagonist tolerance. The mechanisms underlying antagonist tolerance are poorly understood. This review provides a summary of the progress and challenges in therapeutic development of chemokine receptor antagonists, discusses the current knowledge of antagonist tolerance, and proposes new avenues for future investigation of this phenomenon. Additionally, it highlights the potential of modern methodologies in revealing novel mechanisms and advancing the development of tolerance-free antagonists.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Endocrinology & Metabolism
Encarnacion Torres, Inmaculada Velasco, Delphine Franssen, Violeta Heras, Francisco Gaytan, Silvia Leon, Victor M. Navarro, Rafael Pineda, M. Luz Candenas, Antonio Romero-Ruiz, Manuel Tena-Sempere
Summary: The study explored the role of NK2R in the neuroendocrine control of the reproductive axis using a novel Tacr2 knockout mouse model. Results showed that NK2R stimulation elicited LH responses in mice, with partial suppression of basal and stimulated LH secretion in Tacr2 knockout mice, impacting LH pulsatility and breeding intervals. NK2R plays a modest role in the gonadotropic axis, overlapping with other tachykinin receptors.
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Chao Yi, Kangzhi Chen, Haiping Liang, Zusheng Wang, Tao Wang, Kai Li, Jiahui Yu, Jiexie Sun, Chuanfei Jin
Summary: This study discovered a series of 3-(difluoromethyl)-1-(phenylsulfonyl)-4-(piperazin-1yl)-1H-indole derivatives as potent 5-HT6R antagonists. Compound 6p showed excellent pharmacokinetic properties in rats and demonstrated potential cognitive-enhancing effects in in vivo models. In combination with donepezil, 6p was able to increase acetylcholine levels in the brain, suggesting its potential as a treatment for Alzheimer's disease.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Xiu-Ning Hu, Dong-Ping Wu, Ye-Peng Xu, Pei-Qiang Huang
Summary: The first organocatalytic asymmetric synthesis of an advanced intermediate of (+)-sarain A was achieved by combining organocatalytic asymmetric Michael addition reaction and a nitrogen-to-carbon chirality transfer. This method allows for the construction of three chiral centers and chemoselective reduction of a key lactam intermediate, providing a tricyclic intermediate with all necessary functionalities for further elaboration into (+)-sarain A.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Review
Obstetrics & Gynecology
Bijal Patel, Waljit S. Dhillo
Summary: Vasomotor symptoms (VMS) during menopause have a significant impact on women's physical and mental well-being. Hormone therapy is the gold-standard treatment, but it has limitations. Recent development of neurokinin 3 receptor (NK3R) antagonists has shown promising results in reducing VMS and improving patients' quality of life.
BEST PRACTICE & RESEARCH CLINICAL OBSTETRICS & GYNAECOLOGY
(2022)
Article
Ophthalmology
Romina Mayra Lasagni Vitar, Marco Barbariga, Philippe Fonteyne, Fabio Bignami, Paolo Rama, Giulio Ferrari
Summary: This study demonstrates that the NK1R antagonist fosaprepitant effectively reduces ocular surface nociception by decreasing SP release and leukocyte infiltration. Fosaprepitant repurposing shows promise for the treatment of ocular pain.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Article
Chemistry, Multidisciplinary
Peter Polak, Janine Cossy
Summary: Good yields of 2-C-glycals and 2-C-ribals were achieved through a nickel-catalyzed cross-coupling reaction between 2-iodoglycals and 2-iodoribals using Grignard reagents. The synthesized compounds were further transformed into 2-C-2-deoxyglycosides, 2-C-diglycosides, and 2'-C-2'-deoxynucleosides. This method was successfully applied to the synthesis of a 2-chloroadenine 2'-deoxyribonucleoside, an important analogue of cladribine and clofarabine used in the treatment of multiple sclerosis and hairy cell leukemia.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Tomas J. Saiegh, Christophe Meyer, Janine Cossy
Summary: Hydroxamates derived from 3-sulfolene-3-carboxylic acid can undergo intra- and intermolecular rhodium(III)-catalyzed heteroannulations, involving C(sp(2))-H bond activation. These reactions provide a direct route to diversely substituted pyridones and pyridines fused to a sulfolene ring. The subsequent cheletropic elimination under microwave irradiation leads to the generation of pyridine ortho-quinodimethanes.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Physical
Ieva Goldberga, Nicolas Patris, Chia-Hsin Chen, Emilie Thomassot, Julien Trebosc, Ivan Hung, Zhehong Gan, Dorothee Berthomieu, Thomas-Xavier Metro, Christian Bonhomme, Christel Gervais, Danielle Laurencin
Summary: Calcium oxalate minerals, particularly the COM phase, play a significant role in pathological calcifications like renal calculi. However, their structure and water dynamics are not fully understood. This study presents a new approach using solid-state NMR to investigate the local structure and dynamics of water molecules in COM, highlighting the importance of these investigations for understanding biologically relevant minerals.
JOURNAL OF PHYSICAL CHEMISTRY C
(2022)
Article
Chemistry, Organic
Thomas Abegg, Janine Cossy, Christophe Meyer
Summary: cis-1,2-Dialkenylcyclopropanes with a vinyl azide group were generated by Knoevenagel condensations and underwent cascade Cope and Winstein [3,3]-sigmatropic rearrangements under mild conditions. This reaction sequence allows for the synthesis of diversely substituted 1,4-cycloheptadienes with a secondary allylic azide containing up to three stereocenters.
Article
Chemistry, Organic
Peter Polak, Janine Cossy
Summary: This study reports the synthesis of 2-C-substituted 5-deoxyglucals from D-ribose using a nickel-catalyzed cross-coupling reaction. The obtained compounds were further transformed into 2-C-substituted 5-deoxyglycosides and 2-C-substituted 5-deoxynucleosides. The work also involves the reassignment of previously published structures.
Correction
Chemistry, Physical
Ieva Goldberga, Nicolas Patris, Chia-Hsin Chen, Emilie Thomassot, Julien Trebosc, Ivan Hung, Zhehong Gan, Dorothee Berthomieu, Thomas-Xavier Metro, Christian Bonhomme, Christel Gervais, Danielle Laurencin
JOURNAL OF PHYSICAL CHEMISTRY C
(2022)
Article
Chemistry, Multidisciplinary
Jessica Spackova, Ieva Goldberga, Rishit Yadav, Guillaume Cazals, Aurelien Lebrun, Pascal Verdie, Thomas-Xavier Metro, Danielle Laurencin
Summary: O-17 NMR spectroscopy is a powerful technique for studying biomolecules. This study presents cost-effective strategies for enriching amino acids and peptides with O-17 using mechanochemistry. The enriched samples showed high levels of enrichment with no loss of purity, making them suitable for future NMR studies.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Physical
Ieva Goldberga, Nicholai D. Jensen, Christele Combes, Frederic Mentink-Vigier, Xiaoling Wang, Ivan Hung, Zhehong Gan, Julien Trebosc, Thomas-Xavier Metro, Christian Bonhomme, Christel Gervais, Danielle Laurencin
Summary: This study investigates the possibility of enriching O-17 isotopes in water molecules within hydrated biominerals using liquid assisted grinding. The results show that the labelled water molecules are mainly located at the core of the crystal structures and can enter the lattice through dissolution/recrystallization or diffusion. This work highlights the importance of high-resolution O-17 NMR in understanding the roles of water as a grinding agent and as a reagent for isotopic enrichment.
FARADAY DISCUSSIONS
(2023)
Article
Chemistry, Organic
Paul C. Ruer, Youssef Nassar, Peter Polak, Janine Cossy
Summary: Five-membered exo-glycals were synthesized from six-membered 2-iodo-endo-glycals through a metal/halogen exchange/ring-opening sequence followed by a cyclization catalyzed by Ag2CO3.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Gautier Felix, Nicolas Fabregue, Cesar Leroy, Thomas-Xavier Metro, Chia-Hsin Chen, Danielle Laurencin
Summary: The use of induction heating (i-BM) allows for heating the reaction media during ball-milling, expanding the nature and number of synthesized products. This method offers the advantages of fast heating, direct adaptability to commercially-available milling equipment, and the option to heat either the walls or the beads of the milling jars. The properties of the heating system can be finely tuned by manipulating the characteristics of the milling system and/or the induction heating conditions. Examples of applications include elucidating reaction mechanisms, synthesizing new molecules, and controlling the physical nature of milling media.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Physical
Gautier Felix, Nicolas Fabregue, Cesar Leroy, Thomas-Xavier Metro, Chia-Hsin Chen, Danielle Laurencin
Summary: While ball-milling is a commonly used tool in synthetic chemistry, heating the reaction media during mechanochemical reactions can further expand the range of products that can be synthesized. This study introduces a new approach using induction heating to heat up the reaction media during ball-milling reactions, with the ability to heat both the walls of the milling jars and the beads themselves. Numerical simulations demonstrate the ability to finely tune the heating system properties, and examples of applications show the potential of this method in elucidating reaction mechanisms, synthesizing new molecules, and controlling milling media properties.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2023)
Article
Chemistry, Multidisciplinary
Elias Abedelnour, Stephanie Ognier, Olivier Venier, Laurent Schio, Michael Tatoulian, Janine Cossy
Summary: This study presents the direct synthesis of trifluoromethyl N,N-aminals from nitrogen containing heterocycles using argon plasma in a continuous flow microreactor without any additives or metal catalysts. The transformation of these compounds to N-trifluoroethyl amines is also reported.
CHEMICAL COMMUNICATIONS
(2023)
Review
Chemistry, Organic
Tomohiro Yasukawa, Katja S. Haheim, Janine Cossy
Summary: This article introduces the synthesis of 1,3-disubstituted bicyclo[1.1.1]pentanes (BCPs) by forming a C-C bond through cross-coupling reactions using transition metal catalysts. Two main strategies are described to obtain these compounds from nucleophilic BCPs or electrophilic BCPs, including relevant mechanisms.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Chemistry, Organic
Janine Cossy, Peter Polak, Paul C. Ruer
Summary: This review focuses on the incorporation of a cyclobutyl substituent in molecules by transition metal-catalyzed cross-coupling, specifically the formation of C-C bonds. Three main strategies are discussed, involving electrophilic or nucleophilic cyclobutane derivatives.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Elias Abedelnour, Stephanie Ognier, Mengxue Zhang, Laurent Schio, Olivier Venier, Janine Cossy, Michael Tatoulian
Summary: The direct N-acylation of amines by esters in a microreactor using argon plasma is presented, resulting in high yields of amides.
CHEMICAL COMMUNICATIONS
(2022)
