Tag: M.W=150-200

Hung, Alvin W.; Silvestre, H. Leonardo; Wen, Shijun; George, Guillaume P. C.; Boland, Jennifer; Blundell, Tom L.; Ciulli, Alessio; Abell, Chris published the artcile< Optimization of Inhibitors of Mycobacterium tuberculosis Pantothenate Synthetase Based on Group Efficiency Analysis>, Recommanded Product: Morpholine-4-sulfonamide, the main research area is Mycobacterium pantothenate synthetase inhibitor preparation design structure activity tuberculostatic; indole derivative preparation Mycobacterium pantothenate synthetase inhibitor structure activity; Mycobacterium tuberculosis; drug design; fragment-based screening; group efficiency; pantothenate synthetase.

Ligand efficiency has proven to be a valuable concept for optimization of leads in the early stages of drug design. Taking this one step further, group efficiency (GE) evaluates the binding efficiency of each appendage of a mol., further fine-tuning the drug design process. Here, GE anal. is used to systematically improve the potency of inhibitors of Mycobacterium tuberculosis pantothenate synthetase, an important target in tuberculosis therapy. Binding efficiencies were found to be distributed unevenly within a lead mol. derived using a fragment-based approach. Substitution of the less efficient parts of the mol. allowed systematic development of more potent compounds This method of dissecting and analyzing different groups within a mol. offers a rational and general way of carrying out lead optimization, with potential broad application within drug discovery.

ChemMedChem published new progress about Binding energy. 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Recommanded Product: Morpholine-4-sulfonamide.

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

Venkateswarlu, Somepalli; Satyanarayana, Meka; Srinivas, Kolla; Aadisudhakar, Kodumuri N. V. V. published the artcile< Synthesis of isomeric angularly fused dihydroquinazolinoquinazolinones and an unusual oxidative rearrangement>, Reference of 5004-88-6, the main research area is dihydroquinazolino quinazolinone preparation cyclization oxidative rearrangement.

Cyclization of 2-(2-aminophenyl)-2,3-dihydroquinazolin-4(1H)-ones onto N1-nitrogen and onto N3-nitrogen leading to 11b,12-dihydro-(13H)-quinazolino[3,4-a]quinazolin-13-ones, e.g., I, and 13,13a-dihydro-(8H)-quinazolino[4,3-b]quinazolin-8-ones, e.g., II, resp., is described for the first time. An unusual dehydrogenative rearrangement of compound I to (8H)-quinazolino[4,3-b]quinazolin-8-one is also described.

Tetrahedron Letters published new progress about Aromatic amides Role: RCT (Reactant), RACT (Reactant or Reagent) (2-aminoaryl). 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, Reference of 5004-88-6.

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

Kerdphon, Sutthichat; Sanghong, Patthadon; Chatwichien, Jaruwan; Choommongkol, Vachira; Rithchumpon, Puracheth; Singh, Thishana; Meepowpan, Puttinan published the artcile< Commercial Copper-Catalyzed Aerobic Oxidative Synthesis of Quinazolinones from 2-Aminobenzamide and Methanol>, Computed Properties of 5004-88-6, the main research area is quinazolinone preparation copper catalyst aerobic oxidation aminobenzamide methanol.

The focus of this study was the development of a new synthetic method for quinazolinones based on the principles of Green Chem. Quinazolinones were synthesized from 2-aminobenzamide using methanol as both the C1 source and a green solvent in the presence of base Cs2CO3. Addnl., a com. available, economical copper complex was used as a catalyst in the reaction. The desired products were achieved in moderate to high yield with up to 99% isolated yield.

European Journal of Organic Chemistry published new progress about Benzamides Role: RCT (Reactant), RACT (Reactant or Reagent) (2-Aminobenzamide). 5004-88-6 belongs to class amides-buliding-blocks, and the molecular formula is C9H12N2O3, Computed Properties of 5004-88-6.

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

van Loevezijn, Arnold; Venhorst, Jennifer; Iwema Bakker, Wouter I.; de Korte, Cor G.; de Looff, Wouter; Verhoog, Stefan; van Wees, Jan-Willem; van Hoeve, Martijn; van de Woestijne, Rob P.; van der Neut, Martina A. W.; Borst, Alice J. M.; van Dongen, Maria J. P.; de Bruin, Natasja M. W. J.; Keizer, Hiskias G.; Kruse, Chris G. published the artcile< N'-(Arylsulfonyl)pyrazoline-1-carboxamidines as Novel, Neutral 5-Hydroxytryptamine 6 Receptor (5-HT6R) Antagonists with Unique Structural Features>, Recommanded Product: 3-Fluorobenzenesulfonamide, the main research area is arylsulfonylpyrazolinecarboxamidine hydroxytryptamine 6 receptor antagonist.

The 5-HT6 receptor (5-HT6R) has been in the spotlight for several years regarding CNS-related diseases. We set out to discover novel, neutral 5-HT6R antagonists to improve off-target selectivity compared to basic amine-containing scaffolds dominating the field. High-throughput screening identified the N’-(sulfonyl)pyrazoline-1-carboxamidine scaffold as a promising neutral core for starting hit-to-lead. Medicinal chem., mol. modeling, small mol. NMR and X-ray crystallog. were subsequently applied to optimize the leads into antagonists displaying high 5-HT6R affinity with optimal off-target selectivity. Unique structural features include a pseudoarom. system and an internal hydrogen bond freezing the bioactive conformation. While physicochem. properties and CNS availability were generally favorable, significant efforts had to be made to improve metabolic stability. The optimized structure 42 (I) is an extremely selective, hERG-free, high-affinity 5-HT6R antagonist showing good human in vitro metabolic stability. Rat pharmacokinetic data were sufficiently good to enable further in vivo profiling.

Journal of Medicinal Chemistry published new progress about 5-HT antagonists (5-HT6). 1524-40-9 belongs to class amides-buliding-blocks, and the molecular formula is C6H6FNO2S, Recommanded Product: 3-Fluorobenzenesulfonamide.

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

Bolli, Martin H.; Boss, Christoph; Binkert, Christoph; Buchmann, Stephan; Bur, Daniel; Hess, Patrick; Iglarz, Marc; Meyer, Solange; Rein, Josiane; Rey, Markus; Treiber, Alexander; Clozel, Martine; Fischli, Walter; Weller, Thomas published the artcile< The Discovery of N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an Orally Active, Potent Dual Endothelin Receptor Antagonist>, SDS of cas: 25999-04-6, the main research area is alkyl sulfamide pyrimidine preparation oral endothelin receptor antagonist antihypertensive.

Starting from the structure of bosentan (1), we embarked on a medicinal chem. program aiming at the identification of novel potent dual endothelin receptor antagonists with high oral efficacy. This led to the discovery of a novel series of alkyl sulfamide substituted pyrimidines. Among these, compound 17 (macitentan, ACT-064992) emerged as particularly interesting as it is a potent inhibitor of ETA with significant affinity for the ETB receptor and shows excellent pharmacokinetic properties and high in vivo efficacy in hypertensive Dahl salt-sensitive rats. Compound 17 successfully completed a long-term phase III clin. trial for pulmonary arterial hypertension.

Journal of Medicinal Chemistry published new progress about Antihypertensives. 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, SDS of cas: 25999-04-6.

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

Safina, Brian S.; McKerrall, Steven J.; Sun, Shaoyi; Chen, Chien-An; Chowdhury, Sultan; Jia, Qi; Li, Jun; Zenova, Alla Y.; Andrez, Jean-Christophe; Bankar, Girish; Bergeron, Philippe; Chang, Jae H.; Chang, Elaine; Chen, Jun; Dean, Richard; Decker, Shannon M.; DiPasquale, Antonio; Focken, Thilo; Hemeon, Ivan; Khakh, Kuldip; Kim, Amy; Kwan, Rainbow; Lindgren, Andrea; Lin, Sophia; Maher, Jonathan; Mezeyova, Janette; Misner, Dinah; Nelkenbrecher, Karen; Pang, Jodie; Reese, Rebecca; Shields, Shannon D.; Sojo, Luis; Sheng, Tao; Verschoof, Henry; Waldbrook, Matthew; Wilson, Michael S.; Xie, Zhiwei; Young, Clint; Zabka, Tanja S.; Hackos, David H.; Ortwine, Daniel F.; White, Andrew D.; Johnson, J. P. Jr.; Robinette, C. Lee; Dehnhardt, Christoph M.; Cohen, Charles J.; Sutherlin, Daniel P. published the artcile< Discovery of Acyl-sulfonamide Nav1.7 Inhibitors GDC-0276 and GDC-0310>, Quality Control of 25999-04-6, the main research area is acyl sulfonamide sodiumv17 inhibitor GDC0276 GDC0310 pain.

Nav1.7 is an extensively investigated target for pain with a strong genetic link in humans, yet in spite of this effort, it remains challenging to identify efficacious, selective, and safe inhibitors. Here, we disclose the discovery and preclin. profile of GDC-0276 (1) and GDC-0310 (2), selective Nav1.7 inhibitors that have completed Phase 1 trials. Our initial search focused on close-in analogs to early compound 3. This resulted in the discovery of GDC-0276 (1), which possessed improved metabolic stability and an acceptable overall pharmacokinetics profile. To further derisk the predicted human pharmacokinetics and enable QD dosing, addnl. optimization of the scaffold was conducted, resulting in the discovery of a novel series of N-benzyl piperidine Nav1.7 inhibitors. Improvement of the metabolic stability by blocking the labile benzylic position led to the discovery of GDC-0310 (2), which possesses improved Nav selectivity and pharmacokinetic profile over 1.

Journal of Medicinal Chemistry published new progress about Analgesics. 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Quality Control of 25999-04-6.

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

Winters, Michael P.; Crysler, Carl; Subasinghe, Nalin; Ryan, Declan; Leong, Lynette; Zhao, Shuyuan; Donatelli, Robert; Yurkow, Edward; Mazzulla, Marie; Boczon, Lisa; Manthey, Carl L.; Molloy, Christopher; Raymond, Holly; Murray, Lynne; McAlonan, Laura; Tomczuk, Bruce published the artcile< Carboxylic acid bioisosteres acylsulfonamides, acylsulfamides, and sulfonylureas as novel antagonists of the CXCR2 receptor>, Application of C4H10N2O3S, the main research area is arylindolebutanamide alkylsulfonyl arylsulfonyl aminosulfonyl preparation CXCR2 antagonist.

A series of novel acylsulfonamide, acylsulfamide, and sulfonylurea bioisosteres of carboxylic acids were prepared as CXCR2 antagonists. Structure-activity relationships are reported for these series. The potent orally bioavailable inhibitor I had excellent PK properties and was active in a lung injury model in hyperoxia-exposed newborn rats.

Bioorganic & Medicinal Chemistry Letters published new progress about CXC chemokine receptor CXCR2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Application of C4H10N2O3S.

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

Chen, Ling; Luo, Guanglin published the artcile< Facile synthesis of acyl sulfonamides from carboxyic acids using the Mukaiyama reagent>, HPLC of Formula: 6961-82-6, the main research area is Mukaiyama reagent carboxylic acid sulfonamide coupling; acyl sulfonamide preparation.

A fast and convenient method using the Mukaiyama reagent was developed to prepare acyl sulfonamides from carboxylic acids and sulfonamides. This methodol. is effective for a range of acids and sulfonamides proceeding in moderate to good yields with the majority of reactions complete within one hour under the optimized condition.

Tetrahedron Letters published new progress about Carboxylic acids Role: RCT (Reactant), RACT (Reactant or Reagent). 6961-82-6 belongs to class amides-buliding-blocks, and the molecular formula is C6H6ClNO2S, HPLC of Formula: 6961-82-6.

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

Ma, Yao; Li, Xueyuan; Pei, Yameng; Ye, Jingjia; Wei, Xiduan; Yang, Jingshu; Si, Guangxu; Tian, Jingyuan; Dong, Yi; Liu, Gang published the artcile< Identification of benzofused five-membered sultams, potent dual NOD1/NOD2 antagonists in vitro and in vivo>, HPLC of Formula: 6961-82-6, the main research area is nucleotide binding oligomerization domains NOD1 NOD2 antagonist NFkappaB MAPK; Dual NOD1/NOD2 antagonist; Five-membered sultams; MAPK signaling; NF-κB signaling.

Nucleotide-binding oligomerization domain-containing proteins 1 and 2 play important roles in immune system activation. Recently, a shift has occurred due to the emerging knowledge that preventing nucleotide-binding oligomerization domains (NODs) signaling could facilitate the treatment of some cancers, which warrants the search for dual antagonists of NOD1 and NOD2. Herein, we undertook the synthesis and identification of a new class of derivatives of dual NOD1/NOD2 antagonists with novel benzofused five-membered sultams. Compound 14k(I) was finally demonstrated to be the most potent mol. that inhibits both NOD1-and NOD2-stimulated NF-κB and MAPK signaling in vitro and in vivo.

European Journal of Medicinal Chemistry published new progress about Caspase recruitment domain-containing protein 15 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study) (inhibitor). 6961-82-6 belongs to class amides-buliding-blocks, and the molecular formula is C6H6ClNO2S, HPLC of Formula: 6961-82-6.

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

Simons, R. Thomas; Scott, Georgia E.; Kanegusuku, Anastasia Gant; Roizen, Jennifer L. published the artcile< Photochemically Mediated Nickel-Catalyzed Synthesis of N-(Hetero)aryl Sulfamides>, Name: Morpholine-4-sulfonamide, the main research area is photocatalyst nickel heteroaryl sulfamide arylbromide arylation.

A general method for the N-arylation of sulfamides with aryl bromides is described. The protocol leverages a dual-catalytic system, with [Ir(ppy)2(dtbbpy)]PF6 as a photosensitizer, NiBr2•glyme as a precatalyst, and DBU as a base, and proceeds at room temperature under visible light irradiation Using these tactics, aryl boronic esters and aryl chlorides can be carried through the reaction untouched. The developed reactions efficiently engage simple bromoarenes and primary sulfamides in between 66% and quant. yields. For more challenging substrates, such as secondary sulfamides, reaction efficiency is documented. Thereby, these methods complement known Buchwald-Hartwig coupling methods for N-arylation of sulfamides. A general method for the N-arylation of sulfamides with aryl bromides is described. The protocol leverages a dual-catalytic system of Ni and a photoexcitable Ir complex and proceeds at room temperature under visible light irradiation Using these tactics, aryl boronic esters and aryl chlorides can be carried through the reaction untouched. Thereby, this method complements known Buchwald-Hartwig coupling methods for N-arylation of sulfamides.

Journal of Organic Chemistry published new progress about Amines Role: RCT (Reactant), RACT (Reactant or Reagent). 25999-04-6 belongs to class amides-buliding-blocks, and the molecular formula is C4H10N2O3S, Name: Morpholine-4-sulfonamide.

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