Heteroaromatic compounds and their use as dopamine D1 ligands

• Main Authors: EFREMOV, IVAN VIKTOROVICH, DAVOREN, JENNIFER ELIZABETH, SUBRAMANYAM, CHAKRAPANI, GRAY, DAVID LAWRENCE FIRMAN, MENTE, SCOT RICHARD, DOUNAY, AMY BETH, GUILMETTE, EDWARD RAYMOND, HENDERSON, JACLYN LOUISE, NASON II, DEANE MILFORD, ALLEN, JOHN ARTHUR, HARRIS, ANTHONY RICHARD, HELAL, CHRISTOPHER JOHN, COE, JOTHAM WADSWORTH, O'NEIL, STEVEN VICTOR, XU, WENJIAN
• Format: Patent
• Language: English
• Published: 23.04.2015
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The present invention provides, in part, compounds of Formula I: and pharmaceutically acceptable salts thereof and N-oxides thereof; processes and intermediates for preparation of; and compositions and uses thereof. The present invention further provides D1 agonists with reduced D1R desensitization, D1 agonists with a reduced - arrestin recruitment activity relative to Dopamine, D1 agonists interacting significantly with the Ser188 but not significantly with the Ser202 of a D1R when binding to the D1R, D1 agonists interacting less strongly with the Asp103 and interacting less strongly with the Ser198 of a D1R when binding to the D1R, and their uses.