Synthesis of Novel Derivatives of Aroylaminoalcohols and 3-Amino-substituted 1-Phenylpropanols with Potential Anti-inflammatory and Immunomodulating Activities

Abstract

The synthesis of aroylaminoalcohols and 3-amino-substituted 1-phenylpropanols is described. These novel basic compounds have potent anti-inflammatory activity, significantly inhibiting rat paw oedema induced by a variety of phlogistic agents as a result of the release of inflammatory mediators such as histamine, 5-hydroxytryptamine, kinins, prostaglandins or leukotrienes. The biological activity of a selected, representative number of these compounds was examined on adjuvant-induced arthritis, a good animal model for rheumatoid arthritis in man. The results show that 3-(1-hydroxymethylpropylamino)-1-phenylpropan-1-one hydrochloride (2) and 3-(3-hydroxypiperidin-1-yl)-1-phenylpropan-1-one hydrochloride (4) effectively suppress the secondary lesions of adjuvant arthritis. 2-(3-Hydroxy-3-phenylpropylamino)-butan-1-ol hydrochloride (6) had no preventive activity in this animal model. In addition, several of the compounds suppressed the mitogenic responses of T-lymphocytes to concanavalin A, suggesting direct or indirect action on lymphocytes and therefore possible immunosuppressive properties. Finally, we investigated the in-vitro effects of compounds 2 and 4 on production of interleukins 1 and 2 (IL-1 and IL-2). We found that compound 4 suppressed the in-vitro production or action of IL-2 and IL-1. In contrast, compound 2 significantly increased the IL-1 activity of arthritic macrophages while reducing the ability of normal and arthritic splenocytes to produce or release IL-2. Our data suggest that compounds 2 and 4 have immunomodulatory properties that influence T lymphocyte functions.

Synthesis and Antiinflammatory Activity of Coumarin Derivatives,

“…It has been presented earlier that coumarin Mannich bases play a significant role as biologically active compounds in various diseases (Figure , structures a−c]. − Mannich bases were also found to act as antiinflammatory agents (Figure , structure d). − …”

“…[13][14][15] Mannich bases were also found to act as antiinflammatory agents (Figure 1, structure d). [16][17][18] Thus, we found it interesting to synthesize some coumarin Mannich bases as possible antiinflammatory agents to examine (a) their ability to inhibit various enzymes involved in the arachidonic acid cascade and (b) their antioxidant behavior. The structure of our derivatives combines the biological active group of 7-OHcoumarin and the amine moiety as a new template for antiinflammatory activity.…”