Background: Compound containing sulfonamide, pyrazole and chalcone groups are important in medicinal chemistry. They have a wide range of biological activities, including carbonic anhydrase (CA) inhibitory activities.

Introduction: Carbonic anhydrase I and II inhibitors are used for the treatment of diseases, such as retinal and cerebral edema (CA I), epilepsy, and glaucoma (CA II). However, the currently available drugs have some limitations or side effects. Thus, there is a need for new drug candidates to overcome these issues. In this study, a series of compounds, (E)-4-(4-(3-aryl)-3-oxoprop-1-en-1-yl)- 3-phenyl-1H-pyrazol-1-yl) benzenesulfonamides MS4-MS10, were designed to discover new CA inhibitors using a hybrid approach.

Methods: Compounds MS4-MS10 were synthesized as shown in Scheme 1, and their chemical structures were confirmed by ¹H NMR, ¹³C NMR, and HRMS spectra. The CAs (E.C.4.2.1.1) inhibitory effects of MS4-MS10 were tested on the hCA I and II isoenzymes using previously reported procedures.

Results: The CA inhibitors MS4–MS10 gave IC₅₀ values (nM) of 27.8–87.3 towards hCA I and 24.4–54.8 towards hCA II while the IC₅₀ values for reference drug acetazolamide were 384.2 (hCA I) and 36.9 (hCA II). MS7 and MS9 exhibited 13.8 (hCA I) and 1.5 (hCA II) times more potent CA inhibition than the reference compound acetazolamide, respectively.

Conclusion: MS7 (Ar: 2,4,5-trimethoxy phenyl) and MS9 (Ar: 3,4-dimethoxy phenyl) were the most promising compounds of our series with the lowest IC₅₀ values towards hCA I and hCA II, respectively, and can be considered for further studies.

背景：含磺酰胺，吡唑和查耳酮基团的化合物在药物化学中很重要。它们具有广泛的生物学活性，包括碳酸酐酶（CA）抑制活性。

简介：碳酸酐酶I和II抑制剂用于治疗疾病，例如视网膜和脑水肿（CA I），癫痫和青光眼（CA II）。但是，当前可用的药物具有某些局限性或副作用。因此，需要新的候选药物来克服这些问题。在这项研究中，一系列化合物，（E）-4-（4-（3-芳基）-3-氧代丙-1-烯-1-基）-3-苯基-1H-吡唑-1-基）苯磺酰胺MS4-MS10被设计为使用混合方法发现新的CA抑制剂。

方法：如方案1所示合成化合物MS4-MS10，并通过¹ H NMR，¹³ C NMR和HRMS光谱确认其化学结构。使用先前报道的程序测试了MS4-MS10对hCA I和II同工酶的CAs（EC4.2.1.1）抑制作用。

结果：CA抑制剂MS4-MS10对hCA I的IC ₅₀值（nM）为27.8–87.3，对hCA II的IC ₅₀值为24.4–54.8，而参考药物乙酰唑胺的IC ₅₀值为384.2（hCA I）和36.9（hCA II） 。MS7和MS9的有效CA抑制作用分别是参比化合物乙酰唑酰胺的13.8（hCA I）和1.5（hCA II）。

结论：MS7（Ar：2,4,5-三甲氧基苯基）和MS9（Ar：3,4-二甲氧基苯基）是我们系列中最有希望的化合物，其对hCA I和hCA II的IC ₅₀值最低，并可以考虑做进一步的研究。