Zhang, Hongjun’s team published research in ACS Medicinal Chemistry Letters in 2020-02-13 | 603122-80-1

ACS Medicinal Chemistry Letters published new progress about Autoimmune disease. 603122-80-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BClO4, Recommanded Product: (2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid.

Zhang, Hongjun; Lapointe, Blair T.; Anthony, Neville; Azevedo, Rita; Cals, Jos; Correll, Craig C.; Daniels, Matthew; Deshmukh, Sujal; van Eenenaam, Hans; Ferguson, Heidi; Hegde, Laxminarayan G.; Karstens, Willem Jan; MacLean, John; Miller, J. Richard; Moy, Lily Y.; Simov, Vladimir; Nagpal, Sunil; Oubrie, Arthur; Palte, Rachel L.; Parthasarathy, Gopal; Sciammetta, Nunzio; van der Stelt, Mario; Woodhouse, Janice D.; Trotter, B. Wesley; Barr, Kenneth published the artcile< Discovery of N-(Indazol-3-yl)piperidine-4-carboxylic Acids as RORγt Allosteric Inhibitors for Autoimmune Diseases>, Recommanded Product: (2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid, the main research area is indazolylpiperidinecarboxylic acid RORgamma allosteric inhibitor autoimmune disease.

The clin. success of anti-IL-17 monoclonal antibodies (i.e., Cosentyx and Taltz) has validated Th17 pathway modulation for the treatment of autoimmune diseases. The nuclear hormone receptor RORγt is a master regulator of Th17 cells and affects the production of a host of cytokines, including IL-17A, IL-17F, IL-22, IL-26, and GM-CSF. Substantial interest has been spurred across both academia and industry to seek small mols. suitable for RORγt inhibition. A variety of RORγt inhibitors have been reported in the past few years, the majority of which are orthosteric binders. Here the authors disclose the discovery and optimization of a class of inhibitors, which bind differently to an allosteric binding pocket. Starting from a weakly active hit 1, a tool compound 14 was quickly identified that demonstrated superior potency, selectivity, and off-target profile. Further optimization focused on improving metabolic stability. Replacing the benzoic acid moiety with piperidinyl carboxylate, modifying the 4-aza-indazole core in 14 to 4-F-indazole, and incorporating a key hydroxyl group led to the discovery of I, which possesses exquisite potency and selectivity, as well as an improved pharmacokinetic profile suitable for oral dosing.

ACS Medicinal Chemistry Letters published new progress about Autoimmune disease. 603122-80-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BClO4, Recommanded Product: (2-Chloro-4-(methoxycarbonyl)phenyl)boronic acid.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Imanishi, Masashi’s team published research in Journal of Medicinal Chemistry in 2008-03-27 | 603122-80-1

Journal of Medicinal Chemistry published new progress about Homo sapiens. 603122-80-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BClO4, Synthetic Route of 603122-80-1.

Imanishi, Masashi; Tomishima, Yasuyo; Itou, Shinji; Hamashima, Hitoshi; Nakajima, Yutaka; Washizuka, Kenichi; Sakurai, Minoru; Matsui, Shigeo; Imamura, Emiko; Ueshima, Koji; Yamamoto, Takao; Yamamoto, Nobuhiro; Ishikawa, Hirofumi; Nakano, Keiko; Unami, Naoko; Hamada, Kaori; Matsumura, Yasuhiro; Takamura, Fujiko; Hattori, Kouji published the artcile< Discovery of a Novel Series of Biphenyl Benzoic Acid Derivatives as Potent and Selective Human β3-Adrenergic Receptor Agonists with Good Oral Bioavailability. Part I>, Synthetic Route of 603122-80-1, the main research area is biphenyl benzoic acid derivative preparation beta adrenergic receptor agonist.

A novel class of biphenyl analogs containing a benzoic acid moiety based on lead compound I have been identified as potent and selective human β3 adrenergic receptor (β3-AR) agonists with good oral bioavailability and long plasma half-life. After further substituent effects were investigated at the terminal Ph ring of lead compound I, it has been discovered that more lipophilic substitution at the R position improved potency and selectivity. As a result of these studies, II and III were identified as the leading candidates with the best balance of potency, selectivity, and pharmacokinetic profiles. In addition, compounds II and III were evaluated to be efficacious for a carbachol-induced increase of intravesical pressure, such as an overactive bladder model in anesthetized dogs. This represents the first demonstrated result dealing with β3-AR agonists.

Journal of Medicinal Chemistry published new progress about Homo sapiens. 603122-80-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BClO4, Synthetic Route of 603122-80-1.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics

Xia, Yuehan’s team published research in European Journal of Medicinal Chemistry in 2021-02-05 | 603122-80-1

European Journal of Medicinal Chemistry published new progress about Cancer immunotherapy. 603122-80-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BClO4, Formula: C8H8BClO4.

Xia, Yuehan; Yu, Mingcheng; Zhao, Yunpeng; Xia, Li; Huang, Yafei; Sun, Nannan; Song, Meiqi; Guo, Huimin; Zhang, Yunyi; Zhu, Di; Xie, Qiong; Wang, Yonghui published the artcile< Discovery of tetrahydroquinolines and benzomorpholines as novel potent RORγt agonists>, Formula: C8H8BClO4, the main research area is tetrahydroquinoline benzomorpholine orphan retinoic acid receptor agonist cancer immunotherapy; Benzomorpholines; Cancer immunotherapy; Functional switch; RORγt agonists; Tetrahydroquinolines.

The retinoic acid receptor-related orphan receptor γt (RORγt) is an important nuclear receptor that regulates the differentiation of Th17 cells and production of interleukin 17(IL-17). RORγt agonists increase basal activity of RORγt and could provide a potential approach to cancer immunotherapy. Herein, hit compound I was identified as a weak RORγt agonist during inhouse library screening. Changes in LHS core of I led to the identification of tetrahydroquinoline compound II as a partial RORγt agonist (maximum act. = 39.3%). Detailed structure-activity relationship on substituent of the LHS core, amide linker and RHS arylsulfonyl moiety was explored and a novel series of tetrahydroquinolines and benzomorpholines was discovered as potent RORγt agonists. Tetrahydroquinoline compound III (EC50 = 8.9 ± 0.4 nM, maximum act. = 104.5%) and benzomorpholine compound IV (EC50 = 7.5 ± 0.6 nM, maximum act. = 105.8%) were representative compounds with high RORγt agonistic activity in dual FRET assay, and they showed good activity in cell-based Gal4 reporter gene assay and Th17 cell differentiation assay (104.5% activation at 300 nM of III; 59.4% activation at 300 nM of IV). The binding modes of III and IV as well as the two RORγt inverse agonists accidentally discovered were also discussed.

European Journal of Medicinal Chemistry published new progress about Cancer immunotherapy. 603122-80-1 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H8BClO4, Formula: C8H8BClO4.

Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics