289061-13-8Relevant articles and documents
Structure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27
Blavier, Jeremy,Charles, Ma?lle,Hanson, Julien,Kronenberger, Thales,Laschet, Céline,Müller, Christa E.,Pillaiyar, Thanigaimalai,Rosato, Francesca,Wozniak, Monika
, (2021/08/27)
GPR27 belongs, with GPR85 and GPR173, to a small subfamily of three receptors called “Super-Conserved Receptors Expressed in the Brain” (SREB). It has been postulated to participate in key physiological processes such as neuronal plasticity, energy metabolism, and pancreatic β-cell insulin secretion and regulation. Recently, we reported the first selective GPR27 agonist, 2,4-dichloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (I, pEC50 6.34, Emax 100%). Here, we describe the synthesis and structure-activity relationships of a series of new derivatives and analogs of I. All products were evaluated for their ability to activate GPR27 in an arrestin recruitment assay. As a result, agonists were identified with a broad range of efficacies including partial and full agonists, showing higher efficacies than the lead compound I. The most potent agonist was 4-chloro-2,5-difluoro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7y, pEC50 6.85, Emax 37%), and the agonists with higher efficacies were 4-chloro-2-methyl-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7p, pEC50 6.04, Emax 123%), and 2-bromo-4-chloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7r, pEC50 5.99, Emax 123%). Docking studies predicted the putative binding site and interactions of agonist 7p with GPR27. Selected potent agonists were found to be soluble and devoid of cellular toxicity within the range of their pharmacological activity. Therefore, they represent important new tools to further characterize the (patho)physiological roles of GPR27.
Synthesis, Computational Docking, and Antimycobacterial Study of Novel N'-phenyl-4-pyrrol-1-yl-benzenesulfonamide Derivatives
Alqahtani, Yahya S.,Joshi, Shrinivas D.,Kumar, S. R. Prem,Pavitra, H.
, p. 405 - 416 (2021/11/22)
Fresh sequences of pyrrole linked N'-phenyl-4-pyrrolyl-benzenesulfonamide derivatives were synthesized by different synthetic methods. Synthesis of the N'-phenyl-4-(1H-pyrrol-1-yl) benzenesulfonamides 5(a-e)/4-(2,5-dimethyl-1H-pyrrol-1-yl)-N'-phenylbenzenesulfonamides 6(a-e) was achieved by refluxing 2,5-dimethoxytetrahydrofuran/hexane 2,5-dione separately in presence of acetic acid. Further, synthesis of N-(4-(N'-phenylsulfamoyl)phenyl)-4-(1H-pyrrol-1-yl)benzamides 8(a-b)/4-(2,5-dimethyl-1H-pyrrol-1-yl)-N-(4-(N'-phenylsulfamoyl)phenyl)benzamides 10(a-b) was achieved by cold stirring of 4-(1H-pyrrol-1-yl)benzoic acid (7)/2,5-dimethyl-1H-pyrrol-1-yl)benzoic acid (9) correspondingly in the presence of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, N', N'-diisopropylethylamine, and Dimethylformamide. In vitro anti-tubercular study of afresh compounds has shown good minimum inhibitory concentration values (0.4-12.5 μg/mL) counter to Mycobacterium tuberculosis H37Rv, while the corresponding study of reported molecules for antibacterial activity disclosed considerable inhibition values (0.4-25 μg/mL) counter to Escherichia coli (Gram-ve) than Staphylococcus aureus (Gram +ve).
Discovery of secondary sulphonamides as IDO1 inhibitors with potent antitumour effects in vivo
Ge, Shushan,Guo, Wenjie,Hu, Yue,Lai, Yisheng,Li, Yuezhen,Liu, Wen,Ma, Xuewei,Wang, Fang,Wang, Yan,Xu, Qiang,Zheng, Yingbo,Zhong, Haiqing,Zou, Yi
, p. 1240 - 1257 (2020/06/18)
Indoleamine 2,3-dioxygenase 1 (IDO1) as a key rate-limiting enzyme in the kynurenine pathway of tryptophan metabolism plays an important role in tumour immune escape. Herein, a variety of secondary sulphonamides were synthesised and evaluated in the HeLa cell-based IDO1/kynurenine assay, leading to the identification of new IDO1 inhibitors. Among them, compounds 5d, 5l and 8g exhibited the strongest inhibitory effect with significantly improved activity over the hit compound BS-1. The in vitro results showed that these compounds could restore the T cell proliferation and inhibit the differentiation of na?ve CD4+ T cell into highly immunosuppressive FoxP3+ regulatory T (Treg) cell without affecting the viability of HeLa cells and the expression of IDO1 protein. Importantly, the pharmacodynamic assay showed that compound 5d possessed potent antitumour effect in both CT26 and B16F1 tumours bearing immunocompetent mice but not in immunodeficient mice. Functionally, subsequent experiments demonstrated that compound 5d could effectively inhibit tumour cell proliferation, induce apoptosis, up-regulate the expression of IFN-γ and granzyme B, and suppress FoxP3+ Treg cell differentiation, thereby activate the immune system. Thus, compound 5d could be a potential and efficacious agent for further evaluation.
Effect of photodynamic antibacterial chemotherapy combined with antibiotics on Gram-positive and gram-negative bacteria
Ilizirov, Yana,Formanovsky, Andrei,Mikhura, Irina,Paitan, Yossi,Nakonechny, Faina,Nisnevitch, Marina
, (2018/12/11)
The well-known and rapidly growing phenomenon of bacterial resistance to antibiotics is caused by uncontrolled, excessive and inappropriate use of antibiotics. One of alternatives to antibiotics is Photodynamic Antibacterial Chemotherapy (PACT). In the present study, the effect of PACT using a photosensitizer Rose Bengal alone and in combination with antibiotics including methicillin and derivatives of sulfanilamide synthesized by us was tested against antibiotic-sensitive and antibiotic-resistant clinical isolates of Gram-positive S. aureus and Gram-negative P. aeruginosa. Antibiotic-sensitive and resistant strains of P. aeruginosa were eradicated by Rose Bengal under illumination and by sulfanilamide but were not inhibited by new sulfanilamide derivatives. No increase in sensitivity of P. aeruginosa cells to sulfanilamide was observed upon a combination of Rose Bengal and sulfanilamide under illumination. All tested S. aureus strains (MSSA and MRSA) were effectively inhibited by PACT. When treated with sub-MIC concentrations of Rose Bengal under illumination, the minimum inhibitory concentrations (MIC) of methicillin decreased significantly for MSSA and MRSA strains. In some cases, antibiotic sensitivity of resistant strains can be restored by combining antibiotics with PACT.
Ultrasound accelerated sulfonylation of amines by p-acetamidobenzenesulfonyl chloride using Mg–Al hydrotalcite as an efficient green base catalyst
Truong, Binh Nhat,Le, Luong Huu,Chau, Duy-Khiem Nguyen,Duus, Fritz,Luu, Thi?Xuan?Thi
, p. 515 - 528 (2016/10/03)
The sulfonylation reaction of various aliphatic, alicyclic, aromatic, and hetero-aromatic amines with p-acetamidobenzenesulfonyl chloride has been investigated using different types of base catalysis under varied reaction conditions. Mg–Al hydrotalcite, characterizable as an inexpensive, reusable, and green solid catalyst, was found to be the most efficient catalyst, when the reaction is carried out in a minimum volume of solvent (acetone). The reaction was found to be accelerated drastically with the support of ultrasound irradiation, affording the sulfonamides in yields better or equivalent to those obtained under the longer lasting conventional stirring conditions.
Pyridazine derivatives and related compounds, part 28.1 pyridazinesulfonamides: Synthesis and antimicrobial activity
El-Mariah, Fatma,Nassar, Ekhlass,Hosny, Mona,Deeb, Ali
experimental part, p. 92 - 102 (2009/04/16)
The reaction of 3-chloropyridazine 1 with N -(un)Substituted 4-aminosulfonamides 3 gave the 3-substituted aminopyridazines 4. Also In addition, pyridazine-3-sulfonamides 7 were prepared from the reaction of pyridazine-3-sulfonylchloride 6 with different amines. All of these derivatives have been characterized by analytical and spectroscopic studies, and also were tested for their in vitro antibacterial and antifungal activity against a variety of microorganisms.
An easy microwave-assisted synthesis of sulfonamides directly from sulfonic acids
De Luca, Lidia,Giacomelli, Giampaolo
, p. 3967 - 3969 (2008/09/19)
(Chemical Equation Presented) An easy and handy synthesis of sulfonamides directly from sulfonic acids or its sodium salts is reported. The reaction is performed under microwave irradiation, has shown a good functional group tolerance, and is high yielding.
NOVEL ADENOSINE A3 RECEPTOR AGONISTS
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Page/Page column 30, (2008/06/13)
The invention realizes that a series of sulfonamido derivatives with a conserved uronamide group at the 5' position provide superior A3 receptor affinity as well as selectivity. These new adenosine agonists are sulfonamido deritatives N-substituted with aliphatic groups (cyclic or linear) or aromatic radicals.
