- INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
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The present invention provides compounds of Formula(I) or a pharmaceutically acceptable salt thereof, which are inhibitors of the ROMK (Kir1.1) channel. The compounds may be used as diuretic and/or natriuretic agents and for the therapy and prophylaxis of medical conditions including cardiovascular diseases such as hypertension, heart failure, kidney disease, edema, and conditions associated with excessive salt and water retention.
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Page/Page column 46
(2014/09/03)
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- 1-(DIHYDRONAPHTHALENYL)PYRIDONES AS MELANIN-CONCENTRATING HORMONE RECEPTOR 1 ANTAGONISTS
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Provided are 1-(dihydronaphthalenyl)pyridones which are antagonists at the melanin-concentrating hormone receptor 1 (MCHR1), pharmaceutical compositions containing them, processes for their preparation, and their use in therapy for the treatment of obesity and diabetes.
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- 1-(DIHYDRONAPHTHALENYL)PYRIDONES AS MELANIN-CONCENTRATING HORMONE RECEPTOR 1 ANTAGONISTS
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This invention relates to novel 1-(dihydronaphthalenyl)pyridones which are antagonists of the melanin-concentrating hormone receptor 1 (MCHR1), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy
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- Overcoming undesirable CYP1A2 inhibition of pyridylnaphthalene-type aldosterone synthase inhibitors: Influence of heteroaryl derivatization on potency and selectivity
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Recently, we reported on the development of potent and selective inhibitors of aldosterone synthase (CYP11B2) for the treatment of congestive heart failure and myocardial fibrosis. A major drawback of these nonsteroidal compounds was a strong inhibition of the hepatic drug-metabolizing enzyme CYP1A2. In the present study, we examined the influence of substituents in the heterocycle of lead structures with a naphthalene molecular scaffold to overcome this unwanted side effect. With respect to CYP11B2 inhibition, some substituents induced a dramatic increase in inhibitory potency. The methoxyalkyl derivatives 22 and 26 are the most potent CYP11B2 inhibitors up to now (IC50 = 0.2 nM). Most compounds also clearly discriminated between CYP11B2 and CYP11B1, and the CYP1A2 potency significantly decreased in some cases (e.g., isoquinoline derivative 30 displayed only 6% CYP1A2 inhibition at 2 μM concentration). Furthermore, isoquinoline derivative 28 proved to be capable of passing the gastrointestinal tract and reached the general circulation after peroral administration to male Wistar rats.
- Heim, Ralf,Lucas, Simon,Grombein, Cornelia M.,Ries, Christina,Schewe, Katarzyna E.,Negri, Matthias,Müller-Vieira, Ursula,Birk, Barbara,Hartmann, Rolf W.
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supporting information; experimental part
p. 5064 - 5074
(2009/07/11)
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- BICYCLIC COMPOUNDS AS SELECTIVE MELANIN CONCENTRATING HORMONE RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OBESITY AND RELATED DISORDERS
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The present invention discloses compounds of Formula I [CHEMICAL FORMULA should be inserted here as it appears in abstract in paper form] Formula I wherein V, W, Y, Z, R1, R2, R3, R4, d, m, n, p and r are herein defined, said compounds being novel antagon
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Page/Page column 30-32
(2008/06/13)
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- HISTAMINE H3 RECEPTOR ANTAGONISTS, PREPARATION AND THERAPEUTIC USES
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The present invention discloses novel compounds of Formula I or pharmaceutically acceptable salts thereof which have histamine-H3 receptor antagonist activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising compounds of Formula I as well as methods of using them to treat obesity and other histamine H3 receptor -related diseases.
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Page/Page column 18-19
(2008/06/13)
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- NITROGEN-CONTAINING SPIROCYCLES
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Spirocycles of general structural formula: STR1 are Class III antiarrhythmic agents.
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