A5085552858- Computational Drug Discovery Methods
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Microbial Natural Products and Biosynthesis
- Quinazolinone synthesis and applications
- Advanced Biosensing Techniques and Applications
- Molecular spectroscopy and chirality
- Synthesis and Biological Evaluation
- Asymmetric Synthesis and Catalysis
- Chemical Synthesis and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Cell Adhesion Molecules Research
- Synthesis and biological activity
- Synthetic Organic Chemistry Methods
- SARS-CoV-2 and COVID-19 Research
- Biochemical and Molecular Research
- Biosimilars and Bioanalytical Methods
- Synthesis and Characterization of Heterocyclic Compounds
- Biochemical and Structural Characterization
- Synthesis and Properties of Aromatic Compounds
- COVID-19 and healthcare impacts
- Asymmetric Hydrogenation and Catalysis
- Mast cells and histamine
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Pharmacological Receptor Mechanisms and Effects
Drugs for Neglected Diseases Initiative
2021-2024
Goethe University Frankfurt
2021
Alzheimer’s Research UK
2021
University of Oxford
2021
Addex Therapeutics (Switzerland)
2013
Granta Design (United Kingdom)
2007-2009
Imperial College London
2001-2004
GlaxoSmithKline (United Kingdom)
2002
Small aromatic ring systems are of central importance in the development novel synthetic protein ligands. Here we generate a complete list 24847 such systems. We call this and associated annotations VEHICLe, which stands for virtual exploratory heterocyclic library. Searches literature compound databases, using as substructure queries, identified only 1701 synthesized. Using carefully validated machine learning approach, were able to estimate that number unpublished, but synthetically...
Eumycetoma is a chronic subcutaneous neglected tropical disease that can be caused by more than 40 different fungal causative agents. The most common agents produce black grains and belong to the orders Sordariales Pleosporales. current antifungal used treat eumycetoma are itraconazole or terbinafine, however, their cure rates low. To find novel drugs for eumycetoma, we screened 400 diverse drug-like molecules from Pandemic Response Box against as part of Open Source Mycetoma initiative...
The current Covid-19 pandemic has underlined the need for a more coordinated and forward-looking investment in search new medicines targeting emerging health care threats. Repositioning currently approved drugs is popular approach to any disease, but it represents first wave of response. Behind this would be second specifically designed therapies based on activities against specific molecular targets or phenotypic assays. Following successful deployment uptake previous open access compound...
(±)-4,12-Dihydroxy[2.2]paracyclophane [(±)-PHANOL] is readily prepared from [2.2]paracyclophane by an improved synthetic protocol. Enzymatic kinetic resolution of its bis-acetate proceeds with good enantioselection. Separation, hydrolysis, and recrystallization provides both enantiomers PHANOL in high enantiopurity.
Ligand-based similarity screening of proprietary pharmaceutical company libraries enables rapid hit to lead investigation a chemotype with anti-<italic>leishmania</italic> activity.
N-Pyrazolylcarboxamides and N-pyrazolylureas represent promising lead compounds for the development of novel antileishmanial drugs. Herein, we report late-stage diversification 3-bromopyrazoles 10 A/B 14 A by Pd-catalyzed Sonogashira Suzuki-Miyaura cross coupling reactions. The electron-withdrawing properties cyano moiety in 4-position pyrazole ring limited acylation primary amino 5-position. large set pyrazoles bearing diverse aryl alkynyl substituents 3-position was prepared...
Abstract 4,12‐Dihydroxy[2.2]paracyclophanediol (PHANOL; 1 ), and its para ‐substituted derivatives 2, 5 7 , were found to catalyse Diels–Alder cycloadditions of α,β‐unsaturated aldehydes or ketones with dienes and/or epoxide ring opening reactions amines. The mode catalysis by the PHANOLs is via double hydrogen bonding two sp 2 lone pairs a carbonyl group epoxide. order activity for reaction essentially correlates expected hydrogen‐bond donor strength based on degree electron‐withdrawing...
Probing multiple proprietary pharmaceutical libraries in parallel via virtual screening allowed rapid expansion of the structure–activity relationship (SAR) around hit compounds with moderate efficacy against Trypanosoma cruzi, causative agent Chagas Disease. A potency-improving scaffold hop, followed by elaboration SAR design guided output phenotypic efforts, identified two promising 54 and 85, which were profiled further pharmacokinetic studies an vivo model T. cruzi infection. Compound 85...
Leishmaniasis is a collection of diseases caused by more than 20 Leishmania parasite species that manifest as either visceral, cutaneous, or mucocutaneous leishmaniasis. Despite the significant mortality and morbidity associated with leishmaniasis, it remains neglected tropical disease. Existing treatments have variable efficacy, toxicity, rising resistance, limited oral bioavailability, which necessitates development novel affordable therapeutics. Here, we report on continued optimization...
Planar chiral PHANOLs have been shown to catalyze Diels-Alder reactions of a,b-unsaturated aldehydes and ketones with various dienes. Rate accelerations up ca. 30-fold were obtained using the electron deficient 4,12-dihydroxy-7,15-dinitro[2.2]paracyclophane as a catalyst. It is proposed that carbonyl group dienophile activated via double hydrogen-bonding mode. Although are inherently chiral, little or no asymmetric induction was observed when enantiopure (R)-PHANOL.
Abstract Three types of modifications antileishmanial pyrazole lead compounds 7 and 8 were conducted to expand understanding the relationships between structural features antileishmanial/antitrypanosomal activity: (1) core was retained or replaced by a 1,2,4‐triazole ring; (2) various aryl moieties including 2‐fluorophenyl, pyridin‐3‐yl pyrazin‐2‐yl rings attached at 3‐position azole; (3) either arylmethylamino ureido substituents introduced 5‐position azole core. The synthesis followed...
Antimicrobial resistance (AMR) is widely acknowledged as one of the most serious public health threats facing world, yet private sector finds it challenging to generate much-needed medicines. As an alternative discovery approach, a small array diarylimidazoles was screened against ESKAPE pathogens, and results were made publicly available through Open Source Antibiotics (OSA) consortium (https://github.com/opensourceantibiotics). Of 18 compounds tested (at 32 μg/mL), 15 showed >90% growth...
An undergraduate laboratory was developed as part of the Drugs for Neglected Diseases initiative's Open Synthesis Network. This activity aimed to develop new compounds efficacious against visceral leishmaniasis. Students successfully synthesized, purified, and characterized ten different benzoxazole amides that were sent biological testing several protozoan parasites. Although all had poor L. donovani, (2, 4, 9) showed moderate T. cruzi, b. rhodesiense, brucei paired with low cell...
The synthesis of a biologically relevant 2-amino-
Antimicrobial resistance (AMR) is widely acknowledged as one of the most serious public health threats facing world, yet private sector finds it challenging to generate much-needed medicines. As an alternative discovery approach, a small array diarylimidazoles was screened against ESKAPE pathogens (https://en.wikipedia.org/wiki/ESKAPE) and results made publicly available through Open Source Antibiotics (OSA) consortium (https://github.com/opensourceantibiotics). Of 18 compounds tested (at 32...
The Neglected Tropical Disease (NTD) Drug Discovery Booster is a collaborative project in early small molecule drug discovery running since 2015 between Drugs for Diseases initiative (DNDi) and pharmaceutical partners across the globe, including Astellas Pharma Ltd., Eisai Co., Shionogi & Ltd. Takeda Pharmaceutical Company Japan, along with AbbVie Inc., Merck KGaA, AstraZeneca plc Celgene Corporation. engages these to share both their experience silico screening as well proprietary chemical...