PMID- 18842034
OWN - NLM
STAT- MEDLINE
DCOM- 20081128
LR  - 20131121
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 51
IP  - 21
DP  - 2008 Nov 13
TI  - Potent, selective and orally bioavailable dihydropyrimidine inhibitors of Rho 
      kinase (ROCK1) as potential therapeutic agents for cardiovascular diseases.
PG  - 6631-4
LID - 10.1021/jm8005096 [doi]
AB  - Recent studies using known Rho-associated kinase isoform 1 (ROCK1) inhibitors 
      along with cellular and molecular biology data have revealed a pivotal role of 
      this enzyme in many aspects of cardiovascular function. Here we report a series 
      of ROCK1 inhibitors which were originally derived from a dihydropyrimidinone core 
      1. Our efforts focused on the optimization of dihydropyrimidine 2, which resulted 
      in the identification of a series of dihydropyrimidines with improved 
      pharmacokinetics and P450 properties.
FAU - Sehon, Clark A
AU  - Sehon CA
AD  - Departments of Medicinal Chemistry, Investigative Biology, Vascular Biology, 
      GlaxoSmithKline, 709 Swedeland Road, King of Prussia, Pennsylvania 19406, USA. 
      clark.a.sehon@gsk.com
FAU - Wang, Gren Z
AU  - Wang GZ
FAU - Viet, Andrew Q
AU  - Viet AQ
FAU - Goodman, Krista B
AU  - Goodman KB
FAU - Dowdell, Sarah E
AU  - Dowdell SE
FAU - Elkins, Patricia A
AU  - Elkins PA
FAU - Semus, Simon F
AU  - Semus SF
FAU - Evans, Christopher
AU  - Evans C
FAU - Jolivette, Larry J
AU  - Jolivette LJ
FAU - Kirkpatrick, Robert B
AU  - Kirkpatrick RB
FAU - Dul, Edward
AU  - Dul E
FAU - Khandekar, Sanjay S
AU  - Khandekar SS
FAU - Yi, Tracey
AU  - Yi T
FAU - Wright, Lois L
AU  - Wright LL
FAU - Smith, Gary K
AU  - Smith GK
FAU - Behm, David J
AU  - Behm DJ
FAU - Bentley, Ross
AU  - Bentley R
FAU - Doe, Christopher P
AU  - Doe CP
FAU - Hu, Erding
AU  - Hu E
FAU - Lee, Dennis
AU  - Lee D
LA  - eng
PT  - Journal Article
DEP - 20081009
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Aldehydes)
RN  - 0 (Indazoles)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - K8CXK5Q32L (pyrimidine)
SB  - IM
MH  - Adenosine Triphosphate/chemistry/metabolism
MH  - Administration, Oral
MH  - Aldehydes/chemistry
MH  - Animals
MH  - Cardiovascular Diseases/*drug therapy/*enzymology
MH  - Crystallography, X-Ray
MH  - Indazoles/chemistry
MH  - Models, Molecular
MH  - Molecular Structure
MH  - Protein Kinase Inhibitors/administration & dosage/*chemistry/*therapeutic use
MH  - Pyrimidines/administration & dosage/*chemistry/*therapeutic use
MH  - Rats
MH  - Structure-Activity Relationship
MH  - rho-Associated Kinases/*antagonists & inhibitors/metabolism
EDAT- 2008/10/10 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/10/10 09:00
PHST- 2008/10/10 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/10/10 09:00 [entrez]
AID - 10.1021/jm8005096 [doi]
PST - ppublish
SO  - J Med Chem. 2008 Nov 13;51(21):6631-4. doi: 10.1021/jm8005096. Epub 2008 Oct 9.