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Use of carbazole compounds for the treatment of congestive heart failure

a technology of congestive heart failure and carbazole, which is applied in the direction of biocide, drug composition, peptide/protein ingredients, etc., can solve the problems of abnormal retention of water, excess mortality, and congestive heart failure, and achieve the effect of decreasing mortality

Inactive Publication Date: 2009-05-05
SMITHKLINE BEECHAM (CORK) LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The present invention provides a new use of compounds that can be used to make medications for treating congestive heart failure. These compounds are dual non-selective β-adrenoceptor and α1-adrenoceptor antagonists. Specifically, carbazolyl-(4)-oxypropanolamine compounds are preferred. These compounds can be used alone or in combination with other therapeutic agents such as ACE inhibitors, diuretics, and cardiac glycosides. The invention provides a method of treatment using these compounds, as well as pharmaceutically acceptable salts of carvedilol."

Problems solved by technology

Congestive heart failure occurs as a result of impaired pumping capability of the heart and is associated with abnormal retention of water and sodium.
Also, congestive heart failure is a well-known cardiac disorder which results in an excess mortality.

Method used

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  • Use of carbazole compounds for the treatment of congestive heart failure
  • Use of carbazole compounds for the treatment of congestive heart failure

Examples

Experimental program
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Effect test

Embodiment Construction

[0007]U.S. Pat. No. 4,503,067 discloses carbazolyl-(4)-oxypropanolamine compounds of Formula I:

[0008]

TABLE 1U.S. Carvedilol Heart Failure Trials-Baseline CharacteristicsPlaceboCarvedilolCharacteristic(n = 356)(n = 624)Age, mean + SD (years)59.9 + 11.758.8 − 11.8Sex (% men)62%62%Etiology (% inchemic)43%40%Severity of CHFClass II41%41%Class III-IV40%39%Unknown19%20%LV ejection fraction, mean + SD0.22 + 0.070.23 − 0.086 Minute walk (m + SD)373 + 88 379 + 81 Blood pressure (mmHg)115 / 73115 / 73Heart rate (bpm + SD)85 ± 1386 ± 13

wherein[0009]R1 is hydrogen, lower alkanoyl of up to 6 carbon atoms or aroyl selected from benzoyl, and naphthoyl;[0010]R2 is hydrogen, lower alkyl of up to 6 carbon atoms or arylakyl selected from benzyl, phenylethyl and phenylpropyl;[0011]R3 is hydrogen or lower alkyl of up to 6 carbon atoms,[0012]R4 is hydrogen or lower alkyl of up to 6 carbon atoms, or when X is oxygen, R4 together with R5 can represent —CH2—O—;[0013]X is a valency bond, —CH2, oxygen or sulfur;[...

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Abstract

A method of treatment using carvedilol is disclosed, wherein the carvedilol decreases the risk of mortality caused by congestive heart failure in patients. The patients are titrated with low amounts of carvedilol, with the initial titration dosage being only 10 to 30% of the daily maintenance dose.

Description

[0001]This application is a 371 of PCT / EP96 / 00498 filed Feb. 7, 1996.FIELD OF THE INVENTION[0002]The present invention relates to a new method of treatment using compounds which are dual non-selective β-adrenoceptor and α1-adrenoceptor antagonists in particular the carbazolyl-(4)-oxypropanolamine compounds of Formula I, preferably carvedilol, for decreasing the mortality of patients suffering from congestive heart failure (CHF). The invention also relates to a method of treatment using compounds which are dual non-selective β-adrenoceptor and α1-adrenoceptor antagonists, in particular the carbazolyl-(4)-oxypropanolamine compounds of Formula I, preferably carvedilol, in conjunction with one or more other therapeutic agents, said agents being selected from the group consisting of angiotensin converting enzyme (ACE) inhibitors, diuretics, and cardiac glycosides, for decreasing the mortality of patients suffering from CHF. The invention further relates to an incremental application sche...

Claims

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Application Information

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Patent Type & Authority Patents(United States)
IPC IPC(8): A61K31/403A61K31/196C07D207/16A61K31/34A61K31/40A61K31/401A61K31/404A61K31/44A61K31/54A61K31/549A61K31/662A61K31/70A61K31/702A61K38/00A61K45/00A61K45/06A61P9/00A61P9/04C07D209/88
CPCA61K31/403A61K31/7048A61P9/00A61P9/04A61K2300/00A61K31/40
Inventor LUKAS-LASKEY, MARY ANNRUFFOLO, JR., ROBERTSHUSTERMAN, NEIL HOWARDSPOONER, GISBERTSTREIN, KLAUS
Owner SMITHKLINE BEECHAM (CORK) LTD
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