PMID- 1409378
OWN - NLM
STAT- MEDLINE
DCOM- 19921116
LR  - 20190818
IS  - 0724-8741 (Print)
IS  - 0724-8741 (Linking)
VI  - 9
IP  - 8
DP  - 1992 Aug
TI  - Pharmacokinetic analysis of the structural requirements for forming "stable" 
      analogues of valpromide.
PG  - 1058-63
AB  - The following valpromide (VPD) analogues were synthesized and their 
      structure-pharmacokinetic relationships explored: 3-ethyl pentanamide (EPD), 
      methylneopentylacetamide (MND), 1-methyl cyclohexanecarboxamide (MCD), 
      cycloheptanecarboxamide (CHD), and t-butylacetamide (TBD). Two aliphatic (EPD and 
      MND) and two cyclic amides (MCD and CHD) underwent complete or partial conversion 
      to their corresponding acids. The only amide found in this study to be "stable" 
      to the amide-acid biotransformation was TBD. It also had the lowest clearance and 
      the longest half-life and mean residence time. Unlike the other investigated 
      amides, TBD contained two substitutions of two methyl moieties at the beta 
      position of its chemical structure. A "stable" valpromide analogue must have 
      either two substitutions at the beta position, such as in the case of TBD, or a 
      substitution in the alpha and beta positions, such as in the case of the VPD 
      isomer valnoctamide (VCD). This paper discusses the antiepileptic potential of 
      stable VPD analogues which may be more potent and less teratogenic than their 
      biotransformed isomers.
FAU - Haj-Yehia, A
AU  - Haj-Yehia A
AD  - Department of Pharmacy, School of Pharmacy, Hebrew University of Jerusalem, 
      Israel.
FAU - Hadad, S
AU  - Hadad S
FAU - Bialer, M
AU  - Bialer M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Pharm Res
JT  - Pharmaceutical research
JID - 8406521
RN  - 614OI1Z5WI (Valproic Acid)
RN  - RUA6CWU76G (dipropylacetamide)
SB  - IM
MH  - Animals
MH  - Biotransformation
MH  - Chromatography, Gas
MH  - Dogs
MH  - Female
MH  - Half-Life
MH  - Magnetic Resonance Spectroscopy
MH  - Male
MH  - Protein Binding
MH  - Solubility
MH  - Stereoisomerism
MH  - Structure-Activity Relationship
MH  - Valproic Acid/*analogs & derivatives/chemistry/pharmacokinetics
EDAT- 1992/08/01 00:00
MHDA- 1992/08/01 00:01
CRDT- 1992/08/01 00:00
PHST- 1992/08/01 00:00 [pubmed]
PHST- 1992/08/01 00:01 [medline]
PHST- 1992/08/01 00:00 [entrez]
AID - 10.1023/a:1015862613315 [doi]
PST - ppublish
SO  - Pharm Res. 1992 Aug;9(8):1058-63. doi: 10.1023/a:1015862613315.