Category: 252932-48-2

Theoclitou, Maria-Elena; Aquila, Brian; Block, Michael H.; Brassil, Patrick J.; Castriotta, Lillian; Code, Erin; Collins, Michael P.; Davies, Audrey M.; Deegan, Tracy; Ezhuthachan, Jayachandran; Filla, Sandra; Freed, Ellen; Hu, Haiqing; Huszar, Dennis; Jayaraman, Muthusamy; Lawson, Deborah; Lewis, Paula M.; Nadella, Murali V. P.; Oza, Vibha; Padmanilayam, Maniyan; Pontz, Timothy; Ronco, Lucienne; Russell, Daniel; Whitston, David; Zheng, Xiaolan published the artcile< Discovery of (+)-N-(3-Aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), a Kinesin Spindle Protein Inhibitor and Potential Anticancer Agent>, Category: esters-buliding-blocks, the main research area is thiazolopyrimidine thienopyrimidine aroylaminoalkyl aminopropyl kinesin spindle protein inhibitor anticancer; pyridopyrimidine pyrrolopyrimidine pyridopyrimidine aroylaminoalkyl aminopropyl kinesin spindle protein inhibitor.

Structure-activity relationship anal. identified (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877), from a series of novel kinesin spindle protein (KSP) inhibitors, as exhibiting both excellent biochem. potency and pharmaceutical properties suitable for clin. development. The selected compound arrested cells in mitosis leading to the formation of the monopolar spindle phenotype characteristic of KSP inhibition and induction of cellular death. A favorable pharmacokinetic profile and notable in vivo efficacy supported the selection of this compound as a clin. candidate for the treatment of cancer.

Journal of Medicinal Chemistry published new progress about Antitumor 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

Guo, Yinping; Mao, Xin; Xiong, Liang; Xia, Anjie; You, Jing; Lin, Guifeng; Wu, Chengyong; Huang, Luyi; Wang, Yiwei; Yang, Shengyong published the artcile< Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain>, Synthetic Route of 252932-48-2, the main research area is cell active SETDB1 tudor domain inhibitor structure guided discovery; SETDB1; epigenetics; structure-based optimization; tool compound; tudor domain.

SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumor suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1, I), we discovered the first potent and selective small mol. SETDB1-TTD inhibitor (R,R)-59 (II) through stepwise structure-guided optimization. (R,R)-59 showed a KD value of 0.088±0.045μM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biol. functions of SETDB1-TTD.

Angewandte Chemie, International Edition published new progress about Antitumor agents. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, Synthetic Route of 252932-48-2.

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

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

Guo, Yinping; Mao, Xin; Xiong, Liang; Xia, Anjie; You, Jing; Lin, Guifeng; Wu, Chengyong; Huang, Luyi; Wang, Yiwei; Yang, Shengyong published the artcile< Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain>, Synthetic Route of 252932-48-2, the main research area is cell active SETDB1 tudor domain inhibitor structure guided discovery; SETDB1; epigenetics; structure-based optimization; tool compound; tudor domain.

SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumor suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1, I), we discovered the first potent and selective small mol. SETDB1-TTD inhibitor (R,R)-59 (II) through stepwise structure-guided optimization. (R,R)-59 showed a KD value of 0.088±0.045μM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biol. functions of SETDB1-TTD.

Angewandte Chemie, International Edition published new progress about Antitumor agents. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, Synthetic Route of 252932-48-2.

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

Guo, Yinping; Mao, Xin; Xiong, Liang; Xia, Anjie; You, Jing; Lin, Guifeng; Wu, Chengyong; Huang, Luyi; Wang, Yiwei; Yang, Shengyong published the artcile< Structure-Guided Discovery of a Potent and Selective Cell-Active Inhibitor of SETDB1 Tudor Domain>, Synthetic Route of 252932-48-2, the main research area is cell active SETDB1 tudor domain inhibitor structure guided discovery; SETDB1; epigenetics; structure-based optimization; tool compound; tudor domain.

SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumor suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound (Cpd1, I), we discovered the first potent and selective small mol. SETDB1-TTD inhibitor (R,R)-59 (II) through stepwise structure-guided optimization. (R,R)-59 showed a KD value of 0.088±0.045μM in the ITC assay. The high potency of (R,R)-59 was well explained by the cocrystal structure of the (R,R)-59-TTD complex. (R,R)-59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer (S,S)-59 did not show activity in all the assays, highlighting the potential of (R,R)-59 as a tool compound in exploring the biol. functions of SETDB1-TTD.

Angewandte Chemie, International Edition published new progress about Antitumor agents. 252932-48-2 belongs to class esters-buliding-blocks, and the molecular formula is C7H10N2O2, Synthetic Route of 252932-48-2.

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