Substituted 4-phenyltetrahydroisoquinolines, pharmaceutical compositions thereof, methods for their preparation and therapeutic use

US7790742B2 · kind B2 · utility

Assignee

• Sanofi-Aventis Deutschland GMBH · DE

Inventors

• Hans-Jochen Lang · Hofheim, DE
• Uwe Heinelt · Wiesbaden, DE
• Klaus Wirth · Frankfurt am Main, DE
• Thomas Licher · Bad Soden, DE
• Armin Hofmeister · Frankfurt, DE

Key dates

• Filing date: Mar 1, 2007
• Grant date: Sep 7, 2010
• Expiry date: May 12, 2029

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D401/12
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present invention relates to substituted 4-phenyltetrahydroisoquinoline compounds of the structure of formula Iand pharmaceutical compositions comprising them wherein the R groups are herein defined. These are excellent inhibitors of the sodium-hydrogen exchanger (NHE), in particular of the sodium-hydrogen exchanger of subtype 3 (NHE3). As such these compounds are useful in the treatment of various disorders of the renal and respiratory systems such as acute or chronic renal failure, pulmonary complications, biliary function disorders, respiratory disorders such as snoring or sleep apneas and cardiovascular/central nervous system disorders such as stroke. More specifically, the present invention relates to substituted 4-phenyl-tetrahydroisoquinolines, derivatives thereof and compositions containing them formulated in combination with other compounds which also regulate the intracellular pH environment such as inhibitors of carbonic anhydrase and inhibitors of the transport systems that carry bicarbonate ions, such as of the sodium-bicarbonate co-transporter (NBC) or the sodium-dependent chloride-bicarbonate exchanger.