Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: CAS:1074-82-4 (1H-isoindole-1,3(2H)-dione)
 25 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3(2H)-dione based HIV-1 integrase inhibitors as display platforms, we undertook a thorough examination of the effects of modifying the halogen substituents on a key benzyl ring that is hypothesized to bind in a hydrophobic pocket of the integrase.DNA complex. Data from this study suggest that in general dihalo-substituted analogues have higher potency than monohalo-substituted compounds, but that further addition of halogens is not beneficial.
 ...
PMID:Examination of halogen substituent effects on HIV-1 integrase inhibitors derived from 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-ones and 4,5-dihydroxy-1H-isoindole-1,3(2H)-diones. 1936 49

Using our recently disclosed 2,3-dihydro-6,7-dihydroxy-1H-isoindol-1-one and 4,5-dihydroxy-1H-isoindole-1,3(2H)-dione integrase inhibitors, we report differential effects on inhibitory potency induced by introduction of an alpha-chiral center into a key aryl substituent. We show that introduction of the chiral center is uniformly deleterious to binding, with the (R)-enantiomer being more deleterious than the (S)-enantiomer. A greater enantiomeric difference in potency is shown by inhibitors that have restricted rotation of the aryl ring, with the larger difference being due to poorer potency of the (R)-enantiomer rather than higher potency of the (S)-enantiomer. The potency difference for enantiomers based on the isoindoline-1,3-dione ring system is less than for those derived from the isoindol-1-one ring system. Our findings provide useful information that should aid in understanding molecular binding interactions of DKA-derived IN inhibitors.
 ...
PMID:Diketoacid-genre HIV-1 integrase inhibitors containing enantiomeric arylamide functionality. 1952 35