PMID- 18307290
OWN - NLM
STAT- MEDLINE
DCOM- 20080611
LR  - 20151119
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 51
IP  - 6
DP  - 2008 Mar 27
TI  - Discovery of a novel series of biphenyl benzoic acid derivatives as potent and 
      selective human beta3-adrenergic receptor agonists with good oral 
      bioavailability. Part I.
PG  - 1925-44
LID - 10.1021/jm701324c [doi]
AB  - A novel class of biphenyl analogues containing a benzoic acid moiety based on 
      lead compound 8i have been identified as potent and selective human beta 3 
      adrenergic receptor (beta 3-AR) agonists with good oral bioavailability and long 
      plasma half-life. After further substituent effects were investigated at the 
      terminal phenyl ring of lead compound 8i, we have discovered that more lipophilic 
      substitution at the R position improved potency and selectivity. As a result of 
      these studies, 10a and 10e were identified as the leading candidates with the 
      best balance of potency, selectivity, and pharmacokinetic profiles. In addition, 
      compounds 10a and 10e were evaluated to be efficacious for a carbachol-induced 
      increase of intravesical pressure, such as an overactive bladder model in 
      anesthetized dogs. This represents the first demonstrated result dealing with 
      beta 3-AR agonists.
FAU - Imanishi, Masashi
AU  - Imanishi M
AD  - Chemistry Research Laboratories, Astellas Pharma Inc., 21 Miyukigaoka, 
      Tsukuba-shi, Ibaraki, Japan.
FAU - Tomishima, Yasuyo
AU  - Tomishima Y
FAU - Itou, Shinji
AU  - Itou S
FAU - Hamashima, Hitoshi
AU  - Hamashima H
FAU - Nakajima, Yutaka
AU  - Nakajima Y
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 - 20080229
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Adrenergic beta-3 Receptor Agonists)
RN  - 0 (Adrenergic beta-Agonists)
RN  - 0 (Benzoates)
RN  - 0 (Biphenyl Compounds)
RN  - 2L9GJK6MGN (diphenyl)
RN  - 8Y164V895Y (Carbachol)
SB  - IM
MH  - Administration, Oral
MH  - *Adrenergic beta-3 Receptor Agonists
MH  - Adrenergic beta-Agonists/chemical synthesis/chemistry/*pharmacology
MH  - Anesthesia
MH  - Animals
MH  - Benzoates/chemical synthesis/chemistry/*pharmacology
MH  - Biological Availability
MH  - Biphenyl Compounds/*chemistry
MH  - Blood Pressure/drug effects
MH  - Carbachol/antagonists & inhibitors/pharmacology
MH  - Dogs
MH  - Drug Design
MH  - Drug Evaluation, Preclinical
MH  - Female
MH  - Humans
MH  - Injections, Intravenous
MH  - Models, Animal
MH  - Molecular Structure
MH  - Stereoisomerism
MH  - Structure-Activity Relationship
MH  - Time Factors
EDAT- 2008/03/01 09:00
MHDA- 2008/06/12 09:00
CRDT- 2008/03/01 09:00
PHST- 2008/03/01 09:00 [pubmed]
PHST- 2008/06/12 09:00 [medline]
PHST- 2008/03/01 09:00 [entrez]
AID - 10.1021/jm701324c [doi]
PST - ppublish
SO  - J Med Chem. 2008 Mar 27;51(6):1925-44. doi: 10.1021/jm701324c. Epub 2008 Feb 29.