- Ferrocene-pyrimidine conjugates: Synthesis, electrochemistry, physicochemical properties and antiplasmodial activities
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The promise of hybrid antimalarial agents and the precedence set by the antimalarial drug ferroquine prompted us to design ferrocene-pyrimidine conjugates. Herein, we report the synthesis, electrochemistry and anti-plasmodial evaluation of ferrocenyl-pyrimidine conjugates against chloroquine susceptible NF54 strain of the malaria parasite Plasmodium falciparum. Also their physicochemical properties have been studied.
- Chopra, Rakesh,De Kock, Carmen,Smith, Peter,Chibale, Kelly,Singh, Kamaljit
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- Interrogation of 2,2′-Bipyrimidines as Low-Potential Two-Electron Electrolytes
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As utilization of renewable energy sources continues to expand, the need for new grid energy storage technologies such as redox flow batteries (RFBs) will be vital. Ultimately, the energy density of a RFB will be dependent on the redox potentials of the respective electrolytes, their solubility, and the number of electrons stored per molecule. With prior literature reports demonstrating the propensity of nitrogen-containing heterocycles to undergo multielectron reduction at low potentials, we focused on the development of a novel electrolyte scaffold based upon a 2,2′-bipyrimidine skeleton. This scaffold is capable of storing two electrons per molecule while also exhibiting a low (~-2.0 V vs Fc/Fc+) reduction potential. A library of 24 potential bipyrimidine anolytes were synthesized and systematically evaluated to unveil structure-function relationships through computational evaluation. Through analysis of these relationships, it was unveiled that steric interactions disrupting the planarity of the system in the reduced state could be responsible for higher levels of degradation in certain anolytes. The major decomposition pathway was ultimately determined to be protonation of the dianion by solvent, which could be reversed by electrochemical or chemical oxidation. To validate the hypothesis of strain-induced decomposition, two new electrolytes with minimal steric encumbrance were synthesized, evaluated, and found to indeed exhibit higher stability than their sterically hindered counterparts.
- Griffin, Jeremy D.,Pancoast, Adam R.,Sigman, Matthew S.
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p. 992 - 1004
(2021/01/25)
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- DIHYDROPYRIMIDINE DERIVATIVES AND USES THEREOF IN THE TREATMENT OF HBV INFECTION OR OF HBV-INDUCED DISEASES
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The application describes dihydropyrimidine derivatives which are useful in the treatment or prevention of HBV infection or of HBV-induced diseases, more particularly of HBV chronic infection or of diseases induced by HBV chronic infection, as well as pharmaceutical or medical applications thereof.
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- Structure elaboration of isoniazid: synthesis, in silico molecular docking and antimycobacterial activity of isoniazid–pyrimidine conjugates
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Abstract: Designing small molecule-based new drug candidates through structure modulation of the existing drugs has drawn considerable attention in view of inevitable emergence of resistance. A new series of isoniazid–pyrimidine conjugates were synthesize
- Kaur, Hardeep,Singh, Lovepreet,Chibale, Kelly,Singh, Kamaljit
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p. 949 - 955
(2019/11/14)
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- COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR
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The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.
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- NOVEL COMPOUNDS AS REARRANGED DURING TRANSFECTION (RET) INHIBITORS
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This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.
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- Primaquine-pyrimidine hybrids: Synthesis and dual-stage antiplasmodial activity
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Abstract A series of novel pyrimidine-primaquine hybrids were synthesized and their effectiveness against the blood and liver stages of malaria parasites was evaluated. The hybrids displayed enhanced liver stage in vitro activity against P. berghei liver
- Kaur, Hardeep,Machado, Marta,De Kock, Carmen,Smith, Peter,Chibale, Kelly,Prudêncio, Miguel,Singh, Kamaljit
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p. 266 - 273
(2015/07/08)
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- INTEGRIN ANTAGONIST CONJUGATES FOR TARGETED DELIVERY TO CELLS EXPRESSING LFA-1
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The invention relates to compounds of formula I: wherein R1, R2, and n are defined in the detailed description and claims. In particular, the present invention relates to the compounds of formula I for use in the manufacture and delivery of conjugated moi
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- PYRIMIDINE AMIDE COMPOUNDS
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Provided herein are compounds of the formula (I): as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of inflammatory diseases and disorders such as, for example, asthma and COPD.
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- 2-Aminopyrimidine based 4-aminoquinoline anti-plasmodial agents. Synthesis, biological activity, structure-activity relationship and mode of action studies
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2-Aminopyrimidine based 4-aminoquinolines were synthesized using an efficacious protocol. Some of the compounds showed in vitro anti-plasmodial activity against drug-sensitive CQS (3D7) and drug-resistant CQ R (K1) strains of Plasmodium falciparum in the nM range. In particular, 5-isopropyloxycarbonyl-6-methyl-4-(2-nitrophenyl)-2-[(7- chloroquinolin-4-ylamino)butylamino] pyrimidine depicted the lowest IC 50 (3.6 nM) value (56-fold less than CQ) against CQR strain. Structure-activity profile and binding with heme, μ-oxo-heme have been studied. Binding assays with DNA revealed better binding with target parasite type AT rich pUC18 DNA. Most compounds were somewhat cytotoxic, but especially cytostatic. Molecular docking analysis with Pf DHFR allowed identification of stabilizing interactions.
- Singh, Kamaljit,Kaur, Hardeep,Chibale, Kelly,Balzarini, Jan,Little, Susan,Bharatam, Prasad V.
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p. 82 - 97
(2012/08/08)
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- DERIVATIVES OF 4-(N-AZACYCLOALKYL) ANILIDES AS POTASSIUM CHANNEL MODULATORS
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This invention provides potassium channel modulators which are compounds of formula I where at least one of W and Z is N; where the moiety is one of Groups A or B below A where Ar is a 1,2-fused, six membered ring aromatic group, bearing substituents R1 and R2 as defined below, and containing zero or one ring nitrogen atom; and where other substituents are defined herein. The invention also provides a composition comprising a pharmaceutically acceptable carrier and at least one of the following: i) a pharmaceutically effective amount of a compound of formula I and ii) a pharmaceutically acceptable salt, ester, or prodrug thereof. The invention also provides a method of preventing or treating a disease or disorder which is affected by activities of potassium channels, comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I or a salt, ester, or prodrug thereof.
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Page/Page column 23
(2009/01/24)
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