PMID- 19647430
OWN - NLM
STAT- MEDLINE
DCOM- 20091124
LR  - 20221207
IS  - 1464-3405 (Electronic)
IS  - 0960-894X (Linking)
VI  - 19
IP  - 17
DP  - 2009 Sep 1
TI  - N-[(3S)-Pyrrolidin-3-yl]benzamides as novel dual serotonin and noradrenaline 
      reuptake inhibitors: impact of small structural modifications on P-gp recognition 
      and CNS penetration.
PG  - 5078-81
LID - 10.1016/j.bmcl.2009.07.049 [doi]
AB  - The structure-activity relationship and the synthesis of novel 
      N-[(3S)-pyrrolidin-3-yl]benzamides as dual serotonin and noradrenaline monoamine 
      reuptake inhibitors (SNRI) is described. Preferred compound 9 aka PF-184,298 is a 
      potent SNRI with good selectivity over dopamine reuptake inhibition (DRI), good 
      in vitro metabolic stability, weak CYP inhibition and drug-like physicochemical 
      properties consistent with CNS target space. Evaluation in an in vivo preclinical 
      model of stress urinary incontinence showed 9 significantly increased urethral 
      tone at free plasma concentrations consistent with its in vitro primary 
      pharmacology.
FAU - Wakenhut, Florian
AU  - Wakenhut F
AD  - Department of Genitourinary Chemistry, Pfizer Global Research and Development, 
      Sandwich Laboratories, Ramsgate Road, Sandwich, Kent, UK. 
      florian.wakenhut@pfizer.com
FAU - Allan, Gill A
AU  - Allan GA
FAU - Fish, Paul V
AU  - Fish PV
FAU - Fray, M Jonathan
AU  - Fray MJ
FAU - Harrison, Anthony C
AU  - Harrison AC
FAU - McCoy, Rachel
AU  - McCoy R
FAU - Phillips, Stephen C
AU  - Phillips SC
FAU - Ryckmans, Thomas
AU  - Ryckmans T
FAU - Stobie, Alan
AU  - Stobie A
FAU - Westbrook, Dominique
AU  - Westbrook D
FAU - Westbrook, Simon L
AU  - Westbrook SL
FAU - Whitlock, Gavin A
AU  - Whitlock GA
LA  - eng
PT  - Journal Article
DEP - 20090731
PL  - England
TA  - Bioorg Med Chem Lett
JT  - Bioorganic & medicinal chemistry letters
JID - 9107377
RN  - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Anilides)
RN  - 0 (Benzamides)
RN  - 0 (Dopamine Uptake Inhibitors)
RN  - 0 (PF 184,298)
RN  - 0 (Pyrrolidines)
RN  - 0 (Serotonin Uptake Inhibitors)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
EIN - Bioorg Med Chem Lett. 2010 Jan 15;20(2):772. Ryckmans, Thomas [added]
MH  - ATP Binding Cassette Transporter, Subfamily B, Member 1/*metabolism
MH  - Adrenergic Uptake Inhibitors/chemical synthesis/*chemistry/pharmacokinetics
MH  - Anilides/chemical synthesis/*chemistry/pharmacology
MH  - Animals
MH  - Benzamides/chemical synthesis/*chemistry/pharmacokinetics
MH  - Cell Line
MH  - Central Nervous System/*metabolism
MH  - Dogs
MH  - Dopamine Uptake Inhibitors/chemical synthesis/chemistry/pharmacokinetics
MH  - Humans
MH  - Norepinephrine/metabolism
MH  - Pyrrolidines/chemical synthesis/*chemistry/pharmacology
MH  - Rats
MH  - Selective Serotonin Reuptake Inhibitors/chemical 
      synthesis/*chemistry/pharmacokinetics
MH  - Structure-Activity Relationship
EDAT- 2009/08/04 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/08/04 09:00
PHST- 2009/06/05 00:00 [received]
PHST- 2009/07/03 00:00 [revised]
PHST- 2009/07/07 00:00 [accepted]
PHST- 2009/08/04 09:00 [entrez]
PHST- 2009/08/04 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - S0960-894X(09)01001-4 [pii]
AID - 10.1016/j.bmcl.2009.07.049 [doi]
PST - ppublish
SO  - Bioorg Med Chem Lett. 2009 Sep 1;19(17):5078-81. doi: 10.1016/j.bmcl.2009.07.049. 
      Epub 2009 Jul 31.