Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5-Triazin-2-one Ring Opening
ChemMedChem. 2023 Dec 21:e202300493. doi: 10.1002/cmdc.202300493. Online ahead of print.ABSTRACTAmidinoureas are an understudied class of molecules with unique structural properties and biological activities. A simple methodology has been developed for the synthesis of aliphatic substituted amidinoureas via unexpected cycle opening of benzothiazolo-1,3,5-triazine-2-ones and transamination reaction of N-(N-(benzo[d]thiazol-2-yl)carbamimidoyl)aniline-1-carboxamide in good yields. A novel series of amidinoureas derivatives was designed, synthesized, and evaluated for its antiproliferative activity on an aggressive metastatic ...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Oleksandr Grytsai Nedra Hamouda-Tekaya Thomas Botton Stephane Rocchi Rachid Benhida Cyril Ronco Source Type: research
Synthesis And Anticancer Activity Of New Hybrid 3-Methylidene-2,3-Dihydro-1,8-Naphthyridinones
ChemMedChem. 2023 Dec 21:e202300519. doi: 10.1002/cmdc.202300519. Online ahead of print.ABSTRACTSynthesis of molecular hybrids, obtained by combination of two or more pharmacophoric groups of different bioactive substances in order to produce more efficient drugs, is now a frequently used approach in medicinal chemistry. Following this strategy, we synthetized a library of 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones, combining a 1,8-naphthyridin-4-one motif with an exo-methylidene bond conjugated with a carbonyl group, pharmacophoric units that are present in many natural, biologically active compounds wi...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Agata Jaskulska Jacek Szyma ński Piotr F J Lipi ński Jakub Modranka Anna E Janecka Tomasz Janecki Katarzyna Gach-Janczak Source Type: research
Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5-Triazin-2-one Ring Opening
ChemMedChem. 2023 Dec 21:e202300493. doi: 10.1002/cmdc.202300493. Online ahead of print.ABSTRACTAmidinoureas are an understudied class of molecules with unique structural properties and biological activities. A simple methodology has been developed for the synthesis of aliphatic substituted amidinoureas via unexpected cycle opening of benzothiazolo-1,3,5-triazine-2-ones and transamination reaction of N-(N-(benzo[d]thiazol-2-yl)carbamimidoyl)aniline-1-carboxamide in good yields. A novel series of amidinoureas derivatives was designed, synthesized, and evaluated for its antiproliferative activity on an aggressive metastatic ...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Oleksandr Grytsai Nedra Hamouda-Tekaya Thomas Botton Stephane Rocchi Rachid Benhida Cyril Ronco Source Type: research
Synthesis And Anticancer Activity Of New Hybrid 3-Methylidene-2,3-Dihydro-1,8-Naphthyridinones
ChemMedChem. 2023 Dec 21:e202300519. doi: 10.1002/cmdc.202300519. Online ahead of print.ABSTRACTSynthesis of molecular hybrids, obtained by combination of two or more pharmacophoric groups of different bioactive substances in order to produce more efficient drugs, is now a frequently used approach in medicinal chemistry. Following this strategy, we synthetized a library of 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones, combining a 1,8-naphthyridin-4-one motif with an exo-methylidene bond conjugated with a carbonyl group, pharmacophoric units that are present in many natural, biologically active compounds wi...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Agata Jaskulska Jacek Szyma ński Piotr F J Lipi ński Jakub Modranka Anna E Janecka Tomasz Janecki Katarzyna Gach-Janczak Source Type: research
Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5-Triazin-2-one Ring Opening
ChemMedChem. 2023 Dec 21:e202300493. doi: 10.1002/cmdc.202300493. Online ahead of print.ABSTRACTAmidinoureas are an understudied class of molecules with unique structural properties and biological activities. A simple methodology has been developed for the synthesis of aliphatic substituted amidinoureas via unexpected cycle opening of benzothiazolo-1,3,5-triazine-2-ones and transamination reaction of N-(N-(benzo[d]thiazol-2-yl)carbamimidoyl)aniline-1-carboxamide in good yields. A novel series of amidinoureas derivatives was designed, synthesized, and evaluated for its antiproliferative activity on an aggressive metastatic ...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Oleksandr Grytsai Nedra Hamouda-Tekaya Thomas Botton Stephane Rocchi Rachid Benhida Cyril Ronco Source Type: research
Synthesis And Anticancer Activity Of New Hybrid 3-Methylidene-2,3-Dihydro-1,8-Naphthyridinones
ChemMedChem. 2023 Dec 21:e202300519. doi: 10.1002/cmdc.202300519. Online ahead of print.ABSTRACTSynthesis of molecular hybrids, obtained by combination of two or more pharmacophoric groups of different bioactive substances in order to produce more efficient drugs, is now a frequently used approach in medicinal chemistry. Following this strategy, we synthetized a library of 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones, combining a 1,8-naphthyridin-4-one motif with an exo-methylidene bond conjugated with a carbonyl group, pharmacophoric units that are present in many natural, biologically active compounds wi...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Agata Jaskulska Jacek Szyma ński Piotr F J Lipi ński Jakub Modranka Anna E Janecka Tomasz Janecki Katarzyna Gach-Janczak Source Type: research
Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5-Triazin-2-one Ring Opening
ChemMedChem. 2023 Dec 21:e202300493. doi: 10.1002/cmdc.202300493. Online ahead of print.ABSTRACTAmidinoureas are an understudied class of molecules with unique structural properties and biological activities. A simple methodology has been developed for the synthesis of aliphatic substituted amidinoureas via unexpected cycle opening of benzothiazolo-1,3,5-triazine-2-ones and transamination reaction of N-(N-(benzo[d]thiazol-2-yl)carbamimidoyl)aniline-1-carboxamide in good yields. A novel series of amidinoureas derivatives was designed, synthesized, and evaluated for its antiproliferative activity on an aggressive metastatic ...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Oleksandr Grytsai Nedra Hamouda-Tekaya Thomas Botton Stephane Rocchi Rachid Benhida Cyril Ronco Source Type: research
Synthesis And Anticancer Activity Of New Hybrid 3-Methylidene-2,3-Dihydro-1,8-Naphthyridinones
ChemMedChem. 2023 Dec 21:e202300519. doi: 10.1002/cmdc.202300519. Online ahead of print.ABSTRACTSynthesis of molecular hybrids, obtained by combination of two or more pharmacophoric groups of different bioactive substances in order to produce more efficient drugs, is now a frequently used approach in medicinal chemistry. Following this strategy, we synthetized a library of 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones, combining a 1,8-naphthyridin-4-one motif with an exo-methylidene bond conjugated with a carbonyl group, pharmacophoric units that are present in many natural, biologically active compounds wi...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Agata Jaskulska Jacek Szyma ński Piotr F J Lipi ński Jakub Modranka Anna E Janecka Tomasz Janecki Katarzyna Gach-Janczak Source Type: research
Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5-Triazin-2-one Ring Opening
ChemMedChem. 2023 Dec 21:e202300493. doi: 10.1002/cmdc.202300493. Online ahead of print.ABSTRACTAmidinoureas are an understudied class of molecules with unique structural properties and biological activities. A simple methodology has been developed for the synthesis of aliphatic substituted amidinoureas via unexpected cycle opening of benzothiazolo-1,3,5-triazine-2-ones and transamination reaction of N-(N-(benzo[d]thiazol-2-yl)carbamimidoyl)aniline-1-carboxamide in good yields. A novel series of amidinoureas derivatives was designed, synthesized, and evaluated for its antiproliferative activity on an aggressive metastatic ...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Oleksandr Grytsai Nedra Hamouda-Tekaya Thomas Botton Stephane Rocchi Rachid Benhida Cyril Ronco Source Type: research
Synthesis And Anticancer Activity Of New Hybrid 3-Methylidene-2,3-Dihydro-1,8-Naphthyridinones
ChemMedChem. 2023 Dec 21:e202300519. doi: 10.1002/cmdc.202300519. Online ahead of print.ABSTRACTSynthesis of molecular hybrids, obtained by combination of two or more pharmacophoric groups of different bioactive substances in order to produce more efficient drugs, is now a frequently used approach in medicinal chemistry. Following this strategy, we synthetized a library of 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones, combining a 1,8-naphthyridin-4-one motif with an exo-methylidene bond conjugated with a carbonyl group, pharmacophoric units that are present in many natural, biologically active compounds wi...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Agata Jaskulska Jacek Szyma ński Piotr F J Lipi ński Jakub Modranka Anna E Janecka Tomasz Janecki Katarzyna Gach-Janczak Source Type: research
Design, Synthesis and Biological Evaluation of Novel Anticancer Amidinourea Analogues via Unexpected 1,3,5-Triazin-2-one Ring Opening
ChemMedChem. 2023 Dec 21:e202300493. doi: 10.1002/cmdc.202300493. Online ahead of print.ABSTRACTAmidinoureas are an understudied class of molecules with unique structural properties and biological activities. A simple methodology has been developed for the synthesis of aliphatic substituted amidinoureas via unexpected cycle opening of benzothiazolo-1,3,5-triazine-2-ones and transamination reaction of N-(N-(benzo[d]thiazol-2-yl)carbamimidoyl)aniline-1-carboxamide in good yields. A novel series of amidinoureas derivatives was designed, synthesized, and evaluated for its antiproliferative activity on an aggressive metastatic ...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Oleksandr Grytsai Nedra Hamouda-Tekaya Thomas Botton Stephane Rocchi Rachid Benhida Cyril Ronco Source Type: research
Synthesis And Anticancer Activity Of New Hybrid 3-Methylidene-2,3-Dihydro-1,8-Naphthyridinones
ChemMedChem. 2023 Dec 21:e202300519. doi: 10.1002/cmdc.202300519. Online ahead of print.ABSTRACTSynthesis of molecular hybrids, obtained by combination of two or more pharmacophoric groups of different bioactive substances in order to produce more efficient drugs, is now a frequently used approach in medicinal chemistry. Following this strategy, we synthetized a library of 3-methylidene-1-tosyl-2,3-dihydro-1,8-naphthyridin-4(1H)-ones, combining a 1,8-naphthyridin-4-one motif with an exo-methylidene bond conjugated with a carbonyl group, pharmacophoric units that are present in many natural, biologically active compounds wi...
Source: ChemMedChem - December 21, 2023 Category: Chemistry Authors: Agata Jaskulska Jacek Szyma ński Piotr F J Lipi ński Jakub Modranka Anna E Janecka Tomasz Janecki Katarzyna Gach-Janczak Source Type: research
Structure-Based Design of AG-946, a Pyruvate Kinase Activator
We describe the structure-based design of compound 27 (AG-946), an activator of PK isoforms, including red blood cell (RBC)-specific isoforms of PK (PKR), designed to have a pseudo-C2-symmetry matching its allosteric binding site on the PK enzyme, which increased its potency towards PKR while reducing activity against off-targets observed from the original scaffold. Compound 27 (AG-946) demonstrated (1) activation of human wild-type PK (half maximal activation concentration [AC50]=0.005 μM) and a panel of mutated PK proteins (K410E [AC50=0.0043 μM] and R510Q [AC50=0.0069 μM]), (2) displayed a significantly longer half-t...
Source: ChemMedChem - December 18, 2023 Category: Chemistry Authors: Tao Liu Anil K Padyana Evan T Judd Lei Jin Dalia Hammoudeh Charles Kung Lenny Dang Source Type: research
Structure-Based Design of AG-946, a Pyruvate Kinase Activator
We describe the structure-based design of compound 27 (AG-946), an activator of PK isoforms, including red blood cell (RBC)-specific isoforms of PK (PKR), designed to have a pseudo-C2-symmetry matching its allosteric binding site on the PK enzyme, which increased its potency towards PKR while reducing activity against off-targets observed from the original scaffold. Compound 27 (AG-946) demonstrated (1) activation of human wild-type PK (half maximal activation concentration [AC50]=0.005 μM) and a panel of mutated PK proteins (K410E [AC50=0.0043 μM] and R510Q [AC50=0.0069 μM]), (2) displayed a significantly longer half-t...
Source: ChemMedChem - December 18, 2023 Category: Chemistry Authors: Tao Liu Anil K Padyana Evan T Judd Lei Jin Dalia Hammoudeh Charles Kung Lenny Dang Source Type: research
Structure-Based Design of AG-946, a Pyruvate Kinase Activator
We describe the structure-based design of compound 27 (AG-946), an activator of PK isoforms, including red blood cell (RBC)-specific isoforms of PK (PKR), designed to have a pseudo-C2-symmetry matching its allosteric binding site on the PK enzyme, which increased its potency towards PKR while reducing activity against off-targets observed from the original scaffold. Compound 27 (AG-946) demonstrated (1) activation of human wild-type PK (half maximal activation concentration [AC50]=0.005 μM) and a panel of mutated PK proteins (K410E [AC50=0.0043 μM] and R510Q [AC50=0.0069 μM]), (2) displayed a significantly longer half-t...
Source: ChemMedChem - December 18, 2023 Category: Chemistry Authors: Tao Liu Anil K Padyana Evan T Judd Lei Jin Dalia Hammoudeh Charles Kung Lenny Dang Source Type: research
