Category: 252932-48-2

Liu, Yan; Haste, Nina M.; Thienphrapa, Wdee; Nizet, Victor; Hensler, Mary; Li, Rongshi published the artcile< Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (I)>, Category: esters-buliding-blocks, the main research area is Staphylococcus methicillin resistance marinopyrrole A antibiotic; MRSA; SAR; antibiotics; asymmetrical marinopyrroles; marinopyrrole.

Infections caused by drug-resistant pathogens are on the rise. The ongoing spread of methicillin-resistant Staphylococcus aureus (MRSA) strains exemplifies the urgent need for new antibiotics. The marine natural product, marinopyrrole A, was previously shown to have potent antibiotic activity against Gram-pos. pathogens, including MRSA. However, its min. inhibitory concentration (MIC) against MRSA was increased by >500 fold in the presence of 20% human serum, thus greatly limiting therapeutic potential. Here we report our discovery of a novel derivative of marinopyrrole A, designated 1a, featuring a 2-4 fold improved MIC against MRSA and significantly less susceptibility to serum inhibition. Importantly, compound 1a displayed rapid and concentration-dependent killing of MRSA. Compared to the natural product counterpart, compound 1a provides an important natural product based scaffold for further Structure Activity Relationship (SAR) and optimization.

Marine Drugs published new progress about Antimicrobial agents. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, Category: esters-buliding-blocks.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Patane, Emanuele; Pittala, Valeria; Guerrera, Francesco; Salerno, Loredana; Romeo, Giuseppe; Siracusa, Maria Angela; Russo, Filippo; Manetti, Fabrizio; Botta, Maurizio; Mereghetti, Ilario; Cagnotto, Alfredo; Mennini, Tiziana published the artcile< Synthesis of 3-Arylpiperazinylalkylpyrrolo[3,2-d]pyrimidine-2,4-dione Derivatives as Novel, Potent, and Selective α1-Adrenoceptor Ligands>, COA of Formula: C7H10N2O2, the main research area is pyrrolopyrimidine dione piperazinylalkyl preparation selective adrenoceptor ligand QSAR.

Novel compounds I [X = (CH2)2, (CH2)3; R1 = H, Ph, 2-ClC6H4, 4-MeC6H4, etc.; R2 = 2-MeOC6H4, 4-MeOC6H4, 2-ClC6H4], characterized by a pyrrolo[3,2-d]pyrimidine-2,4-dione (PPm) system connected through an alkyl chain to a phenylpiperazine (PPz) residue, were designed as structural analogs of the α1-adrenoceptor (α1-AR) ligand RN5. In this new series of derivatives, the indole nucleus of RN5 was replaced by an arylpyrrolo moiety. Several structural modifications were performed on the PPm and PPz moieties and the connecting alkyl chain. These compounds were synthesized and tested in radioligand binding experiments where many of them showed interesting binding profiles. Some compounds, including I [X = (CH2)2; R1 = 2-ClC6H4, 4-ClC6H4, 4-MeC6H4; R2 = 2-ClC6H4], displayed substantial α1-AR selectivity with respect to serotoninergic 5-HT1A and dopaminergic D1 and D2 receptors. Two different mol. modeling approaches (pharmacophoric mapping and quant. structure-affinity relationship anal.) have been applied to rationalize, at a quant. level, the relationships between affinity toward α1-ARs and the structure of the studied compounds Several QSAR models have been reported and described, accounting for the influence of various mol. portions on such affinity data.

Journal of Medicinal Chemistry published new progress about Pharmacophores. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, COA of Formula: C7H10N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Liu, Yan; Haste, Nina M.; Thienphrapa, Wdee; Nizet, Victor; Hensler, Mary; Li, Rongshi published the artcile< Marinopyrrole derivatives as potential antibiotic agents against methicillin-resistant Staphylococcus aureus (I)>, Category: esters-buliding-blocks, the main research area is Staphylococcus methicillin resistance marinopyrrole A antibiotic; MRSA; SAR; antibiotics; asymmetrical marinopyrroles; marinopyrrole.

Infections caused by drug-resistant pathogens are on the rise. The ongoing spread of methicillin-resistant Staphylococcus aureus (MRSA) strains exemplifies the urgent need for new antibiotics. The marine natural product, marinopyrrole A, was previously shown to have potent antibiotic activity against Gram-pos. pathogens, including MRSA. However, its min. inhibitory concentration (MIC) against MRSA was increased by >500 fold in the presence of 20% human serum, thus greatly limiting therapeutic potential. Here we report our discovery of a novel derivative of marinopyrrole A, designated 1a, featuring a 2-4 fold improved MIC against MRSA and significantly less susceptibility to serum inhibition. Importantly, compound 1a displayed rapid and concentration-dependent killing of MRSA. Compared to the natural product counterpart, compound 1a provides an important natural product based scaffold for further Structure Activity Relationship (SAR) and optimization.

Marine Drugs published new progress about Antimicrobial agents. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, Category: esters-buliding-blocks.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Patane, Emanuele; Pittala, Valeria; Guerrera, Francesco; Salerno, Loredana; Romeo, Giuseppe; Siracusa, Maria Angela; Russo, Filippo; Manetti, Fabrizio; Botta, Maurizio; Mereghetti, Ilario; Cagnotto, Alfredo; Mennini, Tiziana published the artcile< Synthesis of 3-Arylpiperazinylalkylpyrrolo[3,2-d]pyrimidine-2,4-dione Derivatives as Novel, Potent, and Selective α1-Adrenoceptor Ligands>, COA of Formula: C7H10N2O2, the main research area is pyrrolopyrimidine dione piperazinylalkyl preparation selective adrenoceptor ligand QSAR.

Novel compounds I [X = (CH2)2, (CH2)3; R1 = H, Ph, 2-ClC6H4, 4-MeC6H4, etc.; R2 = 2-MeOC6H4, 4-MeOC6H4, 2-ClC6H4], characterized by a pyrrolo[3,2-d]pyrimidine-2,4-dione (PPm) system connected through an alkyl chain to a phenylpiperazine (PPz) residue, were designed as structural analogs of the α1-adrenoceptor (α1-AR) ligand RN5. In this new series of derivatives, the indole nucleus of RN5 was replaced by an arylpyrrolo moiety. Several structural modifications were performed on the PPm and PPz moieties and the connecting alkyl chain. These compounds were synthesized and tested in radioligand binding experiments where many of them showed interesting binding profiles. Some compounds, including I [X = (CH2)2; R1 = 2-ClC6H4, 4-ClC6H4, 4-MeC6H4; R2 = 2-ClC6H4], displayed substantial α1-AR selectivity with respect to serotoninergic 5-HT1A and dopaminergic D1 and D2 receptors. Two different mol. modeling approaches (pharmacophoric mapping and quant. structure-affinity relationship anal.) have been applied to rationalize, at a quant. level, the relationships between affinity toward α1-ARs and the structure of the studied compounds Several QSAR models have been reported and described, accounting for the influence of various mol. portions on such affinity data.

Journal of Medicinal Chemistry published new progress about Pharmacophores. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, COA of Formula: C7H10N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Hughes, Chambers C.; Kauffman, Christopher A.; Jensen, Paul R.; Fenical, William published the artcile< Structures, Reactivities, and Antibiotic Properties of the Marinopyrroles A-F>, Related Products of 252932-48-2, the main research area is antimicrobial antitumor marinopyrrole isolation preparation structure activity.

Cultivation of actinomycete strain CNQ-418, retrieved from a deep ocean sediment sample off the coast of La Jolla, CA, has provided marinopyrroles A-F. Sharing just 98% 16S rRNA gene sequence identity with S. sannurensis, the strain likely represents a new Streptomyces species. The metabolites contain an unusual 1,3′-bipyrrole core decorated with several chlorine and bromine substituents and possess marked antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The congested N,C-biaryl bond establishes an axis of chirality that, for marinopyrroles A-E, is configurationally stable at room temperature Moreover, the natural products are fashioned strictly in the M-configuration. The Paal-Knorr condensation was adapted for the synthesis of the 1,3′-bipyrrole core. Halogenation of this material with N-bromosuccinimide cleanly furnished the 4,4′,5,5′-tetrahalogenated core that characterizes this class of marine-derived metabolites.

Journal of Organic Chemistry published new progress about Actinobacteria. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, Related Products of 252932-48-2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Hughes, Chambers C.; Kauffman, Christopher A.; Jensen, Paul R.; Fenical, William published the artcile< Structures, Reactivities, and Antibiotic Properties of the Marinopyrroles A-F>, Related Products of 252932-48-2, the main research area is antimicrobial antitumor marinopyrrole isolation preparation structure activity.

Cultivation of actinomycete strain CNQ-418, retrieved from a deep ocean sediment sample off the coast of La Jolla, CA, has provided marinopyrroles A-F. Sharing just 98% 16S rRNA gene sequence identity with S. sannurensis, the strain likely represents a new Streptomyces species. The metabolites contain an unusual 1,3′-bipyrrole core decorated with several chlorine and bromine substituents and possess marked antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The congested N,C-biaryl bond establishes an axis of chirality that, for marinopyrroles A-E, is configurationally stable at room temperature Moreover, the natural products are fashioned strictly in the M-configuration. The Paal-Knorr condensation was adapted for the synthesis of the 1,3′-bipyrrole core. Halogenation of this material with N-bromosuccinimide cleanly furnished the 4,4′,5,5′-tetrahalogenated core that characterizes this class of marine-derived metabolites.

Journal of Organic Chemistry published new progress about Actinobacteria. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, Related Products of 252932-48-2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics