A series of terminal nonyl chain and nucleobase modified analogues of (+)-EHNA (III) were synthesized and evaluated for their ability to inhibit adenosine deaminase (ADA). The constrained carbon analogues of (+)-EHNA, 7a-7h, 10a-c, 12, 13, 14 and 17a-c appeared very potent with Ki values in the low nanomolar range. Thio-analogues of (+)-EHNA 24a-e wherein 5′C of nonyl chain replaced by sulfur atom found to be less potent compared to (+)-EHNA. Docking of the representative compounds into the active site of ADA was performed to understand structure-activity relationships. Compounds 7a (Ki: 1.1 nM) 7b (Ki: 5.2 nM) and 26a (Ki: 5.9 nM) showed suitable balance of potency, microsomal stability and demonstrated better pharmacokinetic properties as compared to (+)-EHNA and therefore may have therapeutic potential for various inflammatory diseases, hypertension and cancer.

合成了一系列（+）-EHNA（III）的末端壬基链和核碱基修饰的类似物，并评估了它们抑制腺苷脱氨酶（ADA）的能力。EHNA， - （+）的约束碳类似物7A - 7H，10A-C ，12，13，14和17A-C出现非常强的与起在低纳摩尔范围内的值。（+）-EHNA 24a - e的硫代类似物其中发现与（+）-EHNA相比，壬基链的5'C被硫原子取代的效力较低。进行代表性化合物对接至ADA的活性位点以了解结构-活性关系。与（+）-EHNA相比，化合物7a（Ki：1.1 nM）7b（Ki：5.2 nM）和26a（Ki：5.9 nM）显示出适当的效能平衡，微粒体稳定性，并显示出更好的药代动力学特性，因此可能具有治疗潜力用于各种炎症性疾病，高血压和癌症。