C32-O-phenalkyl ether derivatives of the immunosuppressant ascomycin: a tether length study

• Published in: Bioorganic & medicinal chemistry letters Vol. 9; no. 14; pp. 2085 - 2088
• Main Authors: Goulet, Mark T., Sinclair, Peter J., Wong, Frederick, Staruch, Mary Jo, Dumont, Francis J., Cryan, John G., Wiederrecht, Gregory J., Wyvratt, Matthew J., Parsons, William H.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 19-07-1999; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Drug Design; Drug Evaluation, Preclinical; Immunomodulators; Immunophilins - metabolism; Immunosuppressive Agents - chemical synthesis; Immunosuppressive Agents - metabolism; Immunosuppressive Agents - pharmacology; Inhibitory Concentration 50; Macrolides - chemical synthesis; Macrolides - pharmacology; Medical sciences; Pharmacology. Drug treatments; Structure-Activity Relationship; T-Lymphocytes - drug effects; Tacrolimus - analogs & derivatives; Tacrolimus - chemistry; Tacrolimus - pharmacology; Tacrolimus Binding Proteins; Cyclohexane derivatives; Ether; Chain length; Lactam; Lactone; Hemiacetal; In vitro; Alkylation; Macrocycle; Immunomodulator; Structure activity relation; Benzenic compound; Immunosuppressive agent; Chemical synthesis; Ethylenic compound; Oxygen nitrogen heterocycle
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00335-2

A tether length study of C32-O-phenalkyl ether derivatives of ascomycin was conducted wherein it was determined that a 2-carbon tether provides optimum in vitro immunosuppressive activity. Oxygen-bearing substituents along the 2-carbon tether can further increase the potency of this design.
A tether length study of C32-O-phenalkyl ether derivatives of ascomycin was conducted wherein it was determined that a 2-carbon tether provides optimum in vitro immunosuppressive activity. Oxygen-bearing substituents along the 2-carbon tether can further increase the potency of this design.