Some chloropyridazine derivatives have shown interesting pharmacodynamics properties in terms of antioxidant 1 and anti-human rotavirus (HRV) activities ( Figure 1). 2,3 To date, however, no study has evaluated the antiproliferative effects of chloropyridazines in other types of human cancer cells.Therefore, the replacement of the heterocycle of chloropyridazines by heteroatoms (or moieties) such as oxygen (O), sulfur (S), selenium (Se), sulfinyl (SO), and sulfonyl (SO 2 ) yields the target compounds ( Figure 1). We designed substituted 3-chloropyridazine derivatives as possible antitumor candidates. These derivatives have three basic structures, namely chloropyridazine region, heteroatoms, and alkyl chain. We made an examination of antiproliferative activities for target chloropyridazines of five groups against breast cancer (MCF-7) and hepatocellular carcinoma (Hep3B) cells in Cell Counting Kit-8 (CCK-8) assays. As a result, we describe herein the preparation of some chloropyridazine derivatives and the refinement of potential proliferative inhibitors on human cancer cell lines.The chloropyridazines were obtained mostly through the substitution reaction. Scheme 1 depicts the preparation of desired substituted chloropyridazine derivatives. We previously reported the synthesis of 3-allylthio-6chloropyridazine in 95% yield through allylthiolation. 4 All 3-alkoxy-6-chloropyridazines 3b-3d and 3-alkylthio-6-chloropyridazines 4b-4e were prepared following the synthetic methods of existing literature. 5,6 The intermediate dichloropyridazinyl diselenide 2 was obtainable from the corresponding 3,6-dichloropyridazine 1 by reaction with sodium diselenide. 7 A synthetic pathway for dipyridyl diselenide has been developed 7,8 and the synthesis of substituted dipyridazinyl diselenide has been reported. 9 We applied a general method of preparing diaryl (or dialkyl) diselenide from diaryl (or dialkyl) halides and sodium diselenide. 10-12 A series of alkylselenylpyridazines 5b-5f was prepared by Se-Se bond cleavage and Se-alkylation.Treatment of alkylthiopyridazines 4a-4e with 35% hydrogen peroxide afforded corresponding alkylsulfinylchloropyridazine 6a-6e and alkylsulfonylchloropyridazine 7a-7e. Target 6a-6e and 7a-7e were synthesized as illustrated in Scheme 1. Figure 1. Bioactive chloropyridazines and target chloropyridazines. Scheme 1. Synthetic routes for target chloropyridazine analogues.