Rich D H, Gesellchen P D, Tong D, Cheung A, Buckner C K
J Med Chem. 1975 Oct;18(10):1004-10. doi: 10.1021/jm00244a011.
A method for the preparation of N-maleoylamino acids and esters is reported. These compounds were shown to inhibit both the oxytocin-induced smooth muscle contraction in the isolated rat uterus and the vasopressin-induced water loss from the isolated toad bladder. The inhibitory ability of the maleimides in the toad bladder assay was found to be related to their corresponding partition coefficients by the equation: log 1/C = -0.055 (log P) 2 + 0.227 log P + 3.96. N-Maleoylamino acids can be coupled to peptides to form alkylating reagents which react rapidly with sulfhydryl groups. The synthesis of [1-(N-maleoylglycyl)cysteinyl]oxytocin (3) and [1=(N-maleoyl-11-aminoundecanoyl)cysteinyl]oxytocin (4) as potential affinity labeling reagents is described. These oxytocin analogs were shown to readily react with sulfhydryl-containing compounds; however, neither 3 nor 4 was seen to inhibit in the rat uterus assay at concentrations up to 3 times 10(-5)M. When tested on the mucosal and serosal surfaces of the toad bladder, assay inhibition was seen only on the mucosal surface. These results are discussed with respect to the possible existence of sulfhydryl groups at neurohypophyseal receptors.
报道了一种制备N-马来酰氨基酸及其酯的方法。这些化合物被证明能抑制离体大鼠子宫中催产素诱导的平滑肌收缩以及离体蟾蜍膀胱中血管加压素诱导的水分流失。在蟾蜍膀胱试验中发现马来酰亚胺的抑制能力与其相应的分配系数通过以下方程相关：log 1/C = -0.055 (log P)² + 0.227 log P + 3.96。N-马来酰氨基酸可与肽偶联形成能与巯基快速反应的烷基化试剂。描述了作为潜在亲和标记试剂的[1-(N-马来酰甘氨酰)半胱氨酰]催产素(3)和[1=(N-马来酰-11-氨基十一烷酰)半胱氨酰]催产素(4)的合成。这些催产素类似物被证明能与含巯基的化合物快速反应；然而，在高达3×10⁻⁵M的浓度下，3和4在大鼠子宫试验中均未表现出抑制作用。在蟾蜍膀胱的黏膜和浆膜表面进行测试时，仅在黏膜表面观察到试验抑制。针对神经垂体受体处可能存在的巯基对这些结果进行了讨论。
