Lin C C, Dubois R J
J Med Chem. 1977 Mar;20(3):337-41. doi: 10.1021/jm00213a004.
A series of pyrimidinylpropenamides 9 and their oxidation products 10 was prepared, as analogues of sparsomycin (1), for antitumor evaluation. Syntheses involved condensation of the appropriate amino alcohol 5 with acid 8. The resulting sulfides 9 were then oxidized with NaIO4 or H2O2 to sulfoxides 10. Activity was studied in lymphocytic leukemia P-338 and KB cell culture. With the exception of the n-decyl analogue, all of the deoxygenated compounds 9 were inactive regardless of the stereochemical form. In the sulfoxide series 10, those compounds prepared with an L configuration at the asymmetric carbon were also inactive. The completely racemic sulfoxides, on the other hand, displayed substantial antitumor activity (ILS = 37-61% in P-388; ED50 = 1.2-2.4 mug/ml in KB) suggesting that both the presence of a sulfoxide moiety and a D configuration at the chiral carbon atom were structural requirements for a positive antitumor response. There appeared to be a large tolerance for the group substituted at the sulfoxide moiety, however.
制备了一系列嘧啶基丙烯酰胺9及其氧化产物10，作为稀疏霉素（1）的类似物用于抗肿瘤评估。合成过程包括适当的氨基醇5与酸8的缩合反应。然后用高碘酸钠或过氧化氢将所得的硫化物9氧化为亚砜10。在淋巴细胞白血病P - 338和KB细胞培养中研究了其活性。除正癸基类似物外，所有脱氧化合物9无论其立体化学形式如何均无活性。在亚砜系列10中，那些在不对称碳上具有L构型的化合物也无活性。另一方面，完全外消旋的亚砜显示出显著的抗肿瘤活性（在P - 388中ILS = 37 - 61%；在KB中ED50 = 1.2 - 2.4μg/ml），这表明亚砜部分的存在以及手性碳原子上的D构型都是产生阳性抗肿瘤反应的结构要求。然而，对于亚砜部分所取代的基团似乎有很大的耐受性。
