1 SUPPORTING INFORMATION 2-Imino-thiazolidin-4-one Derivatives as Potent, Orally Active S1P 1 Receptor Agonists Martin H. Bolli*, Stefan Abele, Christoph Binkert, Roberto Bravo, Stephan Buchmann, Daniel Bur, John Gatfield, Patrick Hess, Christopher Kohl, Céline Mangold, Boris Mathys, Katalin Menyhart, Claus Müller, Oliver Nayler, Michael Scherz, Gunther Schmidt, Virginie Sippel, Beat Steiner, Daniel Strasser, Alexander Treiber and Thomas Weller. Drug Discovery Chemistry, Actelion Pharmaceuticals Ltd., Gewerbestrasse 16, CH-4123 Allschwil, Switzerland. *To whom correspondence should be addressed. Phone: + 41 61 565 65 70. Fax: + 41 61 565 65 00. E-mail: martin.bolli@actelion.com. Contents Page Preparation of 2-imino-thiazolidin-4-ones 3b-3j, for Table 1 2 Preparation of 2-imino-thiazolidin-4-ones 4b-4j, for Table 1 5 Preparation of 2-imino-thiazolidin-4-ones 5b-5j, for Table 1 8 Preparation of 2-imino-thiazolidin-4-ones 6b-6j, for Table 1 11 Preparation of 2-Imino-thiazolidin-4-ones 9a-19a, for the preparation of compounds 8 discussed in Table 2 14 2-Imino-thiazolidin-4-ones 3k-3y, for the preparation of compounds 8 discussed in Table 3 17 Supplementary analytical data of compound 2 20 Analytical data and X-ray crystallographic structure parameters of compound 2 piperidine co-crystals 20 Preparation and supplementary analytical data of compounds 8a to 8bn and 8bp 22 Combustion Analysis Summary 39 Membrane binding assay 40 Metabolic stability in liver microsomes and hepatocytes 40 Pharmacokinetics in the rat 41 References 42