PMID- 18651730
OWN - NLM
STAT- MEDLINE
DCOM- 20080908
LR  - 20151119
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 51
IP  - 15
DP  - 2008 Aug 14
TI  - Discovery of a novel series of benzoic acid derivatives as potent and selective 
      human beta3 adrenergic receptor agonists with good oral bioavailability. 3. 
      Phenylethanolaminotetraline (PEAT) skeleton containing biphenyl or biphenyl ether 
      moiety.
PG  - 4804-22
LID - 10.1021/jm800222k [doi]
AB  - We designed a series of benzoic acid derivatives containing the biphenyl ether or 
      biphenyl template on the RHS and a phenylethanolaminotetraline (PEAT) skeleton, 
      which was prepared by highly stereoselective synthesis, to generate two 
      structurally different lead compounds ( 10c, 10m) with a good balance of potency, 
      selectivity, and pharmacokinetic profile. Further optimization of the two lead 
      compounds to improve potency led to several potential candidates (i.e., 11f, 11l, 
      11o, 12b). In particular, biphenyl analogue 12b exhibited an excellent balance of 
      high potency (EC50 = 0.38 nM) for beta3, high selectivity over beta1 and beta2, 
      and good pharmacokinetic properties in rats, dogs, and monkeys.
FAU - Imanishi, Masashi
AU  - Imanishi M
AD  - Chemistry Research Laboratories, Pharmacological Research Laboratories, Applied 
      Pharmacology Research Laboratories, Astellas Pharma Inc, Tsukuba-shi, Ibaraki, 
      Japan.
FAU - Nakajima, Yutaka
AU  - Nakajima Y
FAU - Tomishima, Yasuyo
AU  - Tomishima Y
FAU - Hamashima, Hitoshi
AU  - Hamashima H
FAU - Washizuka, Kenichi
AU  - Washizuka K
FAU - Sakurai, Minoru
AU  - Sakurai M
FAU - Matsui, Shigeo
AU  - Matsui S
FAU - Imamura, Emiko
AU  - Imamura E
FAU - Ueshima, Koji
AU  - Ueshima K
FAU - Yamamoto, Takao
AU  - Yamamoto T
FAU - Yamamoto, Nobuhiro
AU  - Yamamoto N
FAU - Ishikawa, Hirofumi
AU  - Ishikawa H
FAU - Nakano, Keiko
AU  - Nakano K
FAU - Unami, Naoko
AU  - Unami N
FAU - Hamada, Kaori
AU  - Hamada K
FAU - Matsumura, Yasuhiro
AU  - Matsumura Y
FAU - Takamura, Fujiko
AU  - Takamura F
FAU - Hattori, Kouji
AU  - Hattori K
LA  - eng
PT  - Journal Article
DEP - 20080724
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Adrenergic Agonists)
RN  - 0 (Adrenergic beta-3 Receptor Agonists)
RN  - 0 (Biphenyl Compounds)
RN  - 0 (Boronic Acids)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Receptors, Adrenergic, beta-3)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0F5N573A2Y (Ether)
RN  - 7568-93-6 (2-Hydroxyphenethylamine)
RN  - 8SKN0B0MIM (Benzoic Acid)
SB  - IM
MH  - 2-Hydroxyphenethylamine/*analogs & derivatives/chemistry
MH  - Administration, Oral
MH  - Adrenergic Agonists/*chemical synthesis/chemistry/*pharmacology
MH  - *Adrenergic beta-3 Receptor Agonists
MH  - Animals
MH  - Benzoic Acid/*chemical synthesis/chemistry/*pharmacology
MH  - Biphenyl Compounds/*chemistry
MH  - Boronic Acids/chemistry
MH  - CHO Cells
MH  - Cricetinae
MH  - Cricetulus
MH  - Dogs
MH  - Epoxy Compounds/administration & dosage/chemistry
MH  - Ether/chemistry
MH  - Humans
MH  - Molecular Structure
MH  - Receptors, Adrenergic, beta-3/metabolism
MH  - Structure-Activity Relationship
MH  - Tetrahydronaphthalenes/*chemistry
EDAT- 2008/07/25 09:00
MHDA- 2008/09/09 09:00
CRDT- 2008/07/25 09:00
PHST- 2008/07/25 09:00 [pubmed]
PHST- 2008/09/09 09:00 [medline]
PHST- 2008/07/25 09:00 [entrez]
AID - 10.1021/jm800222k [doi]
PST - ppublish
SO  - J Med Chem. 2008 Aug 14;51(15):4804-22. doi: 10.1021/jm800222k. Epub 2008 Jul 24.