nipecotic-acid--(s)-isomer and guvacine

nipecotic-acid--(s)-isomer has been researched along with guvacine* in 1 studies

Other Studies

1 other study(ies) available for nipecotic-acid--(s)-isomer and guvacine

Article	Year
Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake. Journal of medicinal chemistry, 1992, Oct-30, Volume: 35, Issue:22 The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of < 1 microM (including 5, Table I; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans. Topics: Administration, Oral; Animals; Anticonvulsants; Benzhydryl Compounds; Blood-Brain Barrier; gamma-Aminobutyric Acid; Humans; In Vitro Techniques; Mice; Neurotransmitter Uptake Inhibitors; Nicotinic Acids; Nipecotic Acids; Proline; Rats; Structure-Activity Relationship	1992

Article

Year

Structure-activity studies on benzhydrol-containing nipecotic acid and guvacine derivatives as potent, orally-active inhibitors of GABA uptake.

Journal of medicinal chemistry, 1992, Oct-30, Volume: 35, Issue:22

The introduction of lipophilic groups onto the ring nitrogen of nipecotic acid and guvacine, two known GABA uptake inhibitors, afforded potent, orally-active anticonvulsant drugs. A series of compounds is reported which explores the structure-activity relationships (SAR) in this series. Among the areas explored: side-chain SAR (aromatic-, heterocyclic-, and tricyclic-containing side chains) and modifications to the tetrahydropyridine ring. The benzhydrol ether-containing side chains afforded the most potent compounds with several exhibiting in vitro IC50 values for GABA uptake of < 1 microM (including 5, Table I; 37, 43, Table IV; and 44, Table V). Compound 44 was selected for extensive evaluation and subsequently progressed to Phase 1 clinical trials with severe adverse effects seen after single dose administration to humans.

Topics: Administration, Oral; Animals; Anticonvulsants; Benzhydryl Compounds; Blood-Brain Barrier; gamma-Aminobutyric Acid; Humans; In Vitro Techniques; Mice; Neurotransmitter Uptake Inhibitors; Nicotinic Acids; Nipecotic Acids; Proline; Rats; Structure-Activity Relationship

1992