A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation.

Background: Exacerbation of heart failure (HF) requires early intervention to prevent hospital admission and to reduce mortality. Early care seeking requires that patients perceive symptoms, accurately evaluate perceived symptoms, and respond appropriately. How perception, evaluation, and response to symptoms are associated with delay in seeking care for worsening symptoms has rarely been studied. Objective: The aims of this study were to investigate the associations of perception of symptoms, evaluation of symptoms, and response to symptoms with delayed care seeking in patients with HF and to identify factors associated with delayed care seeking. Methods: Patients admitted for acute exacerbation of HF were enrolled in this cross-sectional observational study. We used structured interviews, questionnaires, and medical record review to collect data. Factors related to delayed care seeking were identified using nonlinear regression. Results: Analysis was performed in 109 patients with HF. The median delay time was 124 hours. Delayed care seeking was associated with younger age and perception of fatigue, whereas evaluation of and response to symptoms were not associated with delay. Conclusions: Few characteristics of the symptom experience are associated with delayed care seeking among patients with HF who experience an exacerbation of symptoms. Further research is needed to determine why early care seeking is difficult among patients with HF.