Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Nitrogen containing other than solely as a nitrogen in an...
Patent
1993-03-22
1995-04-11
Dees, Jose G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Nitrogen containing other than solely as a nitrogen in an...
564 99, A61K 3118
Patent
active
054058724
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
This invention relates to tetralin derivatives useful in medicine for the treatment of hypertension, to the synthesis of the compounds, to pharmaceutical formulations containing the compounds and the use of the compounds in medical practice.
BACKGROUND INFORMATION
Hypertension may be defined as a condition of sustained elevated arterial blood pressure, i.e., a diastolic pressure in excess of 90 mm Hg. In the majority of cases, the patients are affected by essential hypertension, which by definition means that the underlying etiologic mechanism(s) is unknown. Regardless of the mechanism, a sustained elevation of blood pressure for a period of time has been shown to result in significant cardiovascular damage throughout the body, e.g., congestive heart failure, coronary artery disease, stroke and progressive renal failure [Veterans Administration Cooperative Study Group on Antihypertensive Agents: Effects of Treatment on Morbidity in Hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg, J.A.M.A., (1967), 202, 1028 and Veterans Administration Cooperative Study Group on Antihypertensive Agents: Effects of Treatment on Morbidity in Hypertension II. Results in patients with diastolic blood pressures averaging 90 through 114 mm Hg, J.A.M.A., (1970), 213, 1143].
The benefits of drug therapy to reduce and control blood pressure have been established [Woods, J. W., Current Therapy, ed. Conn, H. F., pp. 219-220, 1981]. Since the specific etiology is not usually known, an empirical approach to the treatment of hypertensive patients is taken. Often, the choice of treatment is based on the severity of the disease and the patient's response and compliance to initial therapy. The goal of the treatment is to reduce elevated blood pressure and maintain pressure at or near normal levels. An antihypertensive agent should be Orally active and have a sufficiently prolonged duration of action to normalize hemodynamic derangements in humans.
European Patent Specification No. 338793 describes certain tetralin sulfonanilides for use in the treatment of prophylaxis of hypertension.
SUMMARY OF THE INVENTION
The compounds of the present invention may be characterized by formula (I) ##STR1## wherein R.sub.1 is hydrogen, hydroxy, C.sub.1-4 alkyl, halo (e.g., chloro), carbamoyl, aminosulfonyl, C.sub.1-4 alkylsulfonylamino or C.sub.1-4 alkyl(C.sub.1-4 alkylsulfonyl)amino; R.sub.2 is hydrogen, hydroxy, halo carbamoyl(e.g., chloro) C.sub.1-4 alkoxycarbonyl, aminosulfonyl or C.sub.1-4 alkylsulfonylamino; R.sub.3 is hydrogen, hydroxy or C.sub.1-4 alkoxy; R.sub.4 is hydrogen, C.sub.1-4 alkoxy, halo (e.g., chloro or bromo) or nitro and pharmaceutically acceptable salts thereof provided that R.sub.1 and R.sub.2 are not both hydrogen and that when R.sub.1 is methylsulfonylamino and R.sub.4 is hydrogen, R.sub.3 is not hydrogen or C.sub.1-4 alkoxy. The invention also includes all enantiomeric and diastereoisomeric forms of the compounds of formula (I), either individually or admixed in any proportions and pharmaceutically acceptable salts thereof.
The compounds of the invention have been found to have advantageous potent antihypertensive properties and are therefore useful in controlling elevated blood pressure in mammals such as humans.
DETAILED DESCRIPTION OF THE INVENTION
Compounds of formula (I) and their salts may be synthesized by methods known in the art for the synthesis of compounds having analogous structures. In particular, compounds of formula (I) and their salts may be prepared by any of the following processes which constitute further aspects of the present invention. For the preparation of compounds of formula (I), a compound of formula (II) ##STR2## wherein R.sub.1 and R.sub.2 are as hereinbefore defined, may be reacted with a compound of formula (IV) ##STR3## wherein R.sub.3 and R.sub.4 are as hereinbefore defined and R is lower alkyl, and R' is lower alkyl or R'R' is an alicyclic ring, or with a compound of formula (III) ##STR4## wherein R.sub.3 and R.sub
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Veterans Administration Cooperative Study Group on Antihypertensive Agents, "Effects of Treatment on Morbidity in Hypertension, Results in Patients with Diastolic Blood Pressure Averaging 115 through 129 mm Hg", JAMA, 202(11), 116-122 (1967).
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Chang Vincent H.
Hurley Kevin P.
McDermed John D.
Tadepalli Anjaneyulu S.
Barts Samuel
Burroughs Wellcome Co.
Dees Jos,e G.
Green Hannah O.
Wasserman Fran S.
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