A Convenient Synthesis of a Selective Gelatinase Inhibitor as an Antimetastatic Agent

• Published in: Journal of organic chemistry Vol. 69; no. 10; pp. 3572 - 3573
• Main Authors: Lim, In Taek, Brown, Stephen, Mobashery, Shahriar
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 14.05.2004; Amer Chemical Soc
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Chemistry; Chemistry, Organic; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; Exact sciences and technology; Gelatinases - antagonists & inhibitors; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Humans; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; DESIGN; POTENT; METASTASIS; MATRIX-METALLOPROTEINASE INHIBITORS; ANGIOGENESIS INHIBITORS; THERAPEUTIC APPLICATION; GROWTH; CANCER; Human; Sulfur heterocycle; Sulfone; Enzyme inhibitor; Antimetastatic agent; Aromatic compound; Selectivity; Malignant tumor; Chemical synthesis
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo049857v

Compound 1, 2-(4-phenoxyphenylsulfonylmethyl)thiirane, is a potent and selective inhibitor for human gelatinases (J. Am. Chem. Soc. 2000, 122, 6799−6800), enzymes implicated in a number of diseases, including cancer. This compound is showing excellent promise in animal trials in a number of disease models. Large quantities of this compound were necessary for these studies. A convenient four-step synthetic route for compound 1 is described herein. The synthesis is amenable to scale-up to tens of grams and gives an overall yield of 57% for this important compound.