(D)-2-tert-Butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid: synthesis and incorporation into the growth hormone secretagogues.
The first enantioselective synthesis of (D)-2-tert-butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid 3 was achieved. The incorporation of the titled compound into growth hormone secretagogue (GHS) compounds resulted in new analogs 10 and 16, both of which had significantly increased in vitro potency. The compound 10 also showed improved in vivo efficacy as well as pharmacokinetic properties in rat models.
Li
Jun
J
Discovery Chemistry, Bristol Myers Squibb, Princeton, NJ 08543, USA. jun.li@bms.com
Chen
Stephanie Y
SY
Murphy
Brian J
BJ
Flynn
Neil
N
Seethala
Ramakrishna
R
Slusarchyk
Dorothy
D
Yan
Mujing
M
Sleph
Paul
P
Zhang
Hongjian
H
Humphreys
William G
WG
Ewing
William R
WR
Robl
Jeffrey A
JA
Gordon
David
D
Tino
Joseph A
JA
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002219:Carbamates / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D013006:Growth Hormone / Q000378:metabolism*; D007211:Indoles / Q000494:pharmacology; D008956:Models, Chemical; D010421:Pentanoic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D036361:Peptide Hormones / Q000737:chemistry; D051381:Rats; D013141:Spiro Compounds / Q000494:pharmacology; D013237:Stereoisomerism; D013777:Tetrazoles / Q000494:pharmacology
C532931:(D)-2-tert-butoxycarbonylamino-5,5-difluoro-5-phenyl-pentanoic acid; C526808:4-(hydroxybutyl)carbamic acid 2-(5-(1-(2-amino-2-methylpropionylamino)-2-benzyloxyethyl)tetrazol-1-yl)ethyl ester; D002219:Carbamates; D007211:Indoles; D010421:Pentanoic Acids; D036361:Peptide Hormones; D013141:Spiro Compounds; D013777:Tetrazoles; D013006:Growth Hormone; C094817:ibutamoren mesylate