Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-07-31
1997-01-14
McKane, Joseph K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
548483, A01N 4352, C07D20910
Patent
active
055940234
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 PCT/FR94/01528 filed Dec. 23, 1994 and published as WO95/18105 Jul. 6, 1995.
The present invention relates to 1,3-dihydroindol-2-one derivatives substituted in the 3-position by a nitrogen-containing group, to their preparation and to the pharmaceutical compositions in which they are present.
The compounds according to the present invention have an affinity for the vasopressin and/or ocytocin receptors.
Vasopressin is a hormone known for its antidiuretic effect and its effect in the regulation of arterial pressure. It stimulates several types of receptors, namely V.sub.1 (V.sub.1a, V.sub.1b) and V.sub.2. These receptors are localized in the liver, vessels (coronary, renal, cerebral), platelets, kidney, uterus, adrenal glands, central nervous system and pituitary gland. Ocytocin has a peptide structure similar to that of vasopressin. The ocytocin receptors are also found on the smooth muscle of the uterus, as well as on myoepithelial cells of the mammary gland, in the central nervous system and in the kidney. The localization of the different receptors is described in: S. JARS et al., Vasopressin and oxytocin receptors: an overview, in Progress in Endocrinology, H. IMURA and K. SHIZURNE ed., Experta Medica, Amsterdam, 1988, 1183-1188, and in the following articles: Presse Medicale, 1987, 16 (10), 481-485; J. Lab. Clin. Med., 1989, 114 (6), 617-632; and Pharmacol. Rev., 1991, 43 (1), 73-108. Vasopressin thus exerts cardiovascular, hepatic, antidiuretic and aggregating effects and effects on the central and peripheral nervous system and in the uterine domain. Ocytocin is involved in parturition, lactation and sexual behavior.
The compounds according to the present invention make it possible selectively either to mimic the effects of the hormone (in the case of agonists) or to inhibit them (in the case of antagonists). Vasopressin receptor antagonists can affect the regulation of the central and peripheral circulation, especially the coronary, renal and gastric circulation, as well as the regulation of hydration and the release of adrenocorticotrophic hormone (ACTH). Vasopressin agonists can advantageously replace vasopressin or its analogs in the treatment of diabetes insipidus; they can also be used in the treatment of enuresis and in the regulation of hemostasis: treatment of hemophilia and von Willebrand's syndrome, antidote to platelet aggregating agents, F. A. LASZLO, Pharmacol. Rev., 1991, 4.3, 73-108; and Drug Investigation, 1990, 2 (Suppl. 5), 1-47. The hormones themselves, namely vasopressin and ocytocin, and some of their peptide or non-peptide analogs are used in therapeutics and have been found to be effective. Several reviews and numerous literature articles may be mentioned: Vasopressin, P. GROSS et al. ed., John Libbey Eurotext, 1993, in particular 243-257 and 549-562; F. A. LASZLO and F. A. LASZLO Jr., Clinical perspectives for vasopressin antagonists, Drug News Perspect., 1993, 6 (8); W. G. NORTH, J. Clin. Endocrinol., 1991, 73, 1316-1320; J. J. LEGROS et al., Prog. Neuro-Pharmacol. Biol. Psychiat., 1988, 12, 571-586; K. E. ANDERSSON et al., Drugs Today, 1988, 24 (7), 509-528; D. L. STUMP et al., Drugs, 1990, 39, 38-53; S. CALTABIANO et al., Drugs Future, 1988, 13, 25-30; Y. MURA et al., Clin. Nephrol., 1993, 40, 60-61; and Faseb J., 1994, 8 (5), A 587, 3398.
Thus the compounds according to the invention are useful especially in the treatment of complaints of the central and peripheral nervous system, the cardiovascular system, the renal domain and the gastric domain and in disorders of sexual behavior, in man and animals.
Patent ZA 83 09532 describes in particular a 1,3-dihydroindol-2-one derivative of the formula ##STR2##
This compound is useful as a converting enzyme inhibitor and as an antihypertensive.
Patent application GB 1 125 671 describes 3-amino-3-arylindolone derivatives of the formula ##STR3## in which: R is hydrogen or a C.sub.1 -C.sub.4 -alkyl or C.sub.1 -C.sub.4 -dialkylamino group; to which they are bonded, are a heterocyclic radical, for example the
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Amiel Marie-Sophie
Di Malta Alain
Roux Richard
Serradeil-Legal Claudine
Tonnerre Bernard
McKane Joseph K.
Oswecki Jane C.
Sanofi
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