- Design and Evaluation of Bispidine-Based SARS-CoV-2 Main Protease Inhibitors
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For the first time, derivatives of 3,7-diazabicyclo[3.3.1]nonane (bispidine) were proposed as potential inhibitors of the SARS-CoV-2 main viral protease (3-chymotrypsin-like, 3CLpro). Based on the created pharmacophore model of the active site of the protease, a group of compounds were modeled and tested for activity against 3CLpro. The 3CLpro activity was measured using the fluorogenic substrate Dabcyl-VNSTLQSGLRK(FAM)MA; the efficiency of the proposed approach was confirmed by comparison with literature data for ebselen and disulfiram. The results of the experiments performed with bispidine compounds showed that 14 compounds exhibited activity in the concentration range 1-10 μM, and 3 samples exhibited submicromolar activity. The structure-activity relationship studies showed that the molecules containing a carbonyl group in the ninth position of the bicycle exhibited the maximum activity. Based on the experimental and theoretical results obtained, further directions for the development of this topic were proposed.
- Baev, Dmitriy,Belenkaya, Svetlana,Chirkova, Varvara,Dalinger, Alexander,Kalinin, Mikhail,Khvostov, Aleksei,Krut'Ko, Dmitry,Maksyutov, Rinat,Medved'Ko, Aleksei,Salakhutdinov, Nariman,Shanshin, Daniil,Sharlaeva, Elena,Shcherbakov, Dmitriy,Tolstikova, Tatyana,Vatsadze, Sergey,Volosnikova, Ekaterina,Yarovaya, Olga
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supporting information
(2021/10/21)
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- Substituted heterocyclic compound containing urea skeleton and preparation method and application of substituted heterocyclic compound
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The invention discloses a substituted heterocyclic compound containing a urea skeleton and a preparation method and application of the substituted heterocyclic compound, and relates to the field of pharmaceutical chemistry, in particular to the substituted heterocyclic compound containing the urea skeleton or pharmaceutically acceptable salt of the substituted heterocyclic compound, a pharmaceutical composition containing the compounds and medical application of the compounds. Particularly, the invention relates to application of the substituted heterocyclic compound as an FAAH inhibitor in preparing drugs for preventing or treating diseases associated with FAAH, such as depression, analgesia, cannabinoid using disorders and other related diseases.
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- FIVE-MEMBERED HETEROCYCLIC AMIDES WNT PATHWAY INHIBITOR
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The present invention discloses a five-membered heterocyclic amide WNT pathway inhibitor, which belongs to a compound that regulates the activity of a Wnt signaling pathway, and provides a method for preparing such a compound, and the use of such a compound in preparing a medicament that antagonizes the Wnt signaling pathway. The five-membered heterocyclic amide WNT pathway inhibitor provided by the invention has a remarkable anti-tumor activity based on a target-based rational drug design of, and can be used for the development of a new generation of Wnt pathway inhibitors, and has a great clinical application value and considerable market potential.
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- Diphenylurea derivatives for combating methicillin- and vancomycin-resistant Staphylococcus aureus
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A new class of diphenylurea was identified as a novel antibacterial scaffold with an antibacterial spectrum that includes highly resistant staphylococcal isolates, namely methicillin- and vancomycin-resistant Staphylococcus aureus (MRSA & VRSA). Starting with a lead compound 3 that carries an aminoguanidine functionality from one side and a n-butyl moiety on the other ring, several analogues were prepared. Considering the pharmacokinetic parameters as a key factor in structural optimization, the structure-activity-relationships (SARs) at the lipophilic side chain were rigorously examined leading to the discovery of the cycloheptyloxyl analogue 21n as a potential drug-candidate. This compound has several notable advantages over vancomycin and linezolid including rapid killing kinetics against MRSA and the ability to target and reduce the burden of MRSA harboring inside immune cells (macrophages). Furthermore, the potent anti-MRSA activity of 21n was confirmed in?vivo using a Caenorhabditis elegans animal model. The present study provides a foundation for further development of diphenylurea compounds as potential therapeutic agents to address the burgeoning challenge of bacterial resistance to antibiotics.
- Eissa, Ibrahim H.,Mohammad, Haroon,Qassem, Omar A.,Younis, Waleed,Abdelghany, Tamer M.,Elshafeey, Ahmed,Abd Rabo Moustafa, Mahmoud M.,Seleem, Mohamed N.,Mayhoub, Abdelrahman S.
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supporting information
p. 73 - 85
(2017/03/02)
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- NOVEL COMPOUND, METHOD FOR PREPARATION THEREOF, AND ANTIFUNGAL COMPOSITION COMPRISING THE SAME
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Disclosed are a compound having an excellent antifungal activity, a composition containing the same, and its use for prevention and treatment of fungal infectious diseases.
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- SUBSTITUTED 1H-PYRAZOL-1,2,4-OXADIAZOLE DERIVATIVES AS SPHINGOSINE RECEPTOR MODULATORS
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The present invention relates to substituted 1H-pyrazol-1,2,4-oxadiazole derivatives, processes for preparing them, pharmaceutical compositions containing them and their use as pharmaceuticals as modulators of sphingosine-1-phosphate receptors.
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Paragraph 199-201
(2014/09/03)
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- HETEROCYCLIC COMPOUND AND p27Kip1 DEGRADATION INHIBITOR
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A novel heterocyclic compound or a salt thereof useful for selectively inhibiting the degradation of p27Kip1 is provided. The compound or the salt thereof is represented by the following formula (1): wherein A represents an alkyl group, a cycloalkyl group, an aryl group or a heterocyclic group, the group A may have a substituent; the ring B represents a 5- to 8-membered monocyclic heterocyclic ring or a condensed ring containing the monocyclic heterocyclic ring, the ring B may have a substituent; the ring C represents an aromatic ring, the ring C may have a substituent; L represents a linker comprising a main chain having 3 to 5 atoms selected from the group consisting of a carbon atom, a nitrogen atom, an oxygen atom and a sulfur atom, wherein at least one atom in the main chain is a hetero atom selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, the linker L may have a substituent; and n is 0 or 1.
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Paragraph 0352; 0353; 0354; 0355; 360
(2013/04/10)
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- AMIDE COMPOUNDS
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The present invention provides compounds represented by the formula (Ia) the formula (Ib) the formula (Ic) and the formula (Id) wherein each symbol is as defined in the specification. According to the present invention, these compounds have a DGAT inhibit
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Page/Page column 260
(2008/06/13)
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- ANTIBACTERIAL BENZOIC ACID DERIVATIVES
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The invention provides antimicrobial agents and methods of using the agents for sterilization, sanitation, antisepsis, disinfection, and treatment of infections in mammals.
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- N-[(substituted five-membered di- or triaza diunsaturated ring)carbonyl] guanidine derivatives for the treatment of ischemia
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NHE-1 inhibitors, methods of using such NHE-1 inhibitors and pharmaceutical compositions containing such NHE-1 inhibitors. The NHE-1 inhibitors are useful for the reduction of tissue damage resulting from tissue ischemia.
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- AMIDE COMPOUNDS AND MEDICINAL USE THEREOF
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The present invention relates to a compound of the formula wherein R1 is substituted aryl, heteroaryl and the like, R2 and R3 are hydrogen, alkyl, halogen, hydroxyl group and the like, Q is N, CH and the like, W is hydrogen, alkyl, hydroxycarbonylalkyl and the like, X is halogen, cyano, nitro, amino and the like, X' is hydrogen, halogen, cyano, nitro, and Y is alkyl, hydroxyl group, alkoxy, mercapto and the like and a salt thereof, and a medicine containing the said compound. The compound of the present invention shows a superior inhibitory effect on activated lymphocytes proliferation and is useful as an agent for the prophylaxis or treatment of various autoimmune diseases.
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