Structure-activity relationship (SAR) of the α-amino acid residue of potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonists.
This letter describes the structure-activity relationship (SAR) of the 'right-wing' α-amino acid residue of potent tetrahydroisoquinoline (THIQ)-derived LFA-1/ICAM-1 antagonists. Novel (S)-substituted heteroaryl-bearing α-amino acids have been identified as replacements of the 'right-wing' (S)-2,3-diaminopropanoic acid (DAP) moiety. Improvement of potency in the Hut-78 assay in the presence of 10% human serum has also been achieved.
Sunesis Pharmaceuticals, Inc, 395 Oyster Point Blvd, Suite 400, South San Francisco, CA 94080, USA. mzhong@presidiopharma.com
Min
M
Zhong
Emily J
EJ
Hanan
Wang
W
Shen
Minna
M
Bui
Michelle R
MR
Arkin
Kenneth J
KJ
Barr
Marc J
MJ
Evanchik
Ute
U
Hoch
Jennifer
J
Hyde
Jose R
JR
Martell
Johan D
JD
Oslob
Kumar
K
Paulvannan
Saileta
S
Prabhu
Jeffrey A
JA
Silverman
Jasmin
J
Wright
Chul H
CH
Yu
Jiang
J
Zhu
W Mike
WM
Flanagan
D000596:Amino Acids / Q000737:chemistry*; D000818:Animals; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry* / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000737:chemistry
D000596:Amino Acids; D016169:Lymphocyte Function-Associated Antigen-1; D044005:Tetrahydroisoquinolines; D015091:beta-Alanine; D018799:Intercellular Adhesion Molecule-1; C011757:2,3-diaminopropionic acid