Organic compounds -- part of the class 532-570 series – Organic compounds – Unsubstituted hydrocarbyl chain between the ring and the -c-...
Patent
1994-08-19
1996-06-25
Raymond, Richard L.
Organic compounds -- part of the class 532-570 series
Organic compounds
Unsubstituted hydrocarbyl chain between the ring and the -c-...
540461, 540476, 540523, 540595, 546141, 546144, 548470, 548486, 548511, 564316, 564336, 564375, 564383, C07D20934, C07D21724, C07D22316
Patent
active
055301258
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to 2,3,4,5-tetrahydro-1H-3-benzazepines having anti-psychotic activity, and also to the synthesis of .alpha.-substituted-arylacetamides, especially fused-ring nitrogen heterocycles, in particular dihydroindoles, 1,2,3,4-tetrahydroisoquinolines and 1,2,3,4,5,6-hexahydro-3-benzazocines, and most particularly 2,3,4,5-tetrahydro-1H-3benzazepines.
Dihydroindoles, 1,2,3,4-tetrahydroisoquinolines, 1,2,3,4,5,6-hexahydro-3-benzazocines, and particularly 2,3,4,5-tetrahydro-1H-3-benzazepines are known to have useful pharmacological properties. For example, U.S. Pat. Nos. 3,393,192, 3,609,138, 4,011,319, 4,284,555 and 4,477,378, and British Patent Specification no. 1,118,688, all describe 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines having various activities described as antibacterial effects, central nervous system effects and hypotensive effects.
Weinstock et al. in Drugs of the Future, Vol. 10, No. 8, pp. 645-697 (1985) discuss the profound effect that 1-phenyl substituents have on the dopaminergic activity of certain types of benzazepines; see in particular Table II on page 666.
European Patent Application No. 83105610.6 (published as 0,096,838) discloses certain 1-aryloxy-2,3,4,5-tetrahydro-1H-3-benzazepines optionally having alkoxy substituents in the 7- and/or 8-position; these compounds are disclosed as having utility in treating depression.
U.S. Pat. No. 5,015,639 describes and claims 2,3,4,5-tetrahydro-1H3-benzazepines lacking a 1-phenyl group but having instead a variety of 1-substituents including a group of the formula ##STR1## wherein m is 0 or 1, and each of the groups R.sup.9, which can be the same or different, is a hydrogen atom or an alkyl, alkoxy, alkoxyalkyl, aralkyl or aryl group. These compounds have good anti-dopaminergic activity, and in particular show surprising selectivity for the D-1 subclassification of dopaminergic receptors. Iorio et al., Pharmacol Exp. Ther. (1983), 226, page 462, and Iorio et al. in Neurobiology of Central D.sub.1 -Dopamine Receptors, pages 1-14 in Advances in Experimental Medicine and Biology 204, Eds. Creese and Breese, Plenum, New York, 1986, have also evaluated the effects of benzazepines on dopamine receptors. Charifson et al., J. Med. Chem. (1988), 31, pages 1941-1946, have similarly evaluated 1,2,3,4-tetrahydroisoquinolines.
International Application No. PCT/US 91/04046 describes and claims (inter alia) compounds having the structural formula A ##STR2## and the pharmaceutically acceptable salts thereof, wherein: R.sup.10 represents H, C.sub.1-4 -alkyl, allyl or cyclopropylmethyl;
These compounds are useful in the treatment of psychoses, depression, pain and hypertension.
Ciufolini et al., Tetrahedron Letters 1987, Vol. 28 No. 2, 171-174, have described a 'model' intramolecular arylation of 2-[2-(2-iodophenyl)ethyl]-indan.alpha.-1,3-dione with tetrakis(triphenylphosphine)palladium(0), to yield a spiro(indane-1,3-dione-2,1'-indane), in experiments on the synthesis of Friedricamycin. In further studies of prototype substrates and also of substrates used in studies of the synthesis of Friedricamycin, Ciufolini et al., J. Org. Chem. [Communications]1988, 53,4149-4151, have described intramolecular arylations of 'soft' enolates (i.e., enolates having a pK.sub.a <15) catalyzed by zerovalent palladium. A phenyl halide moiety in one part of the molecule was condensed with an enol in another part of the molecule to provide a benzo-fused five- or six-membered homocyclic or heterocyclic ring; but compounds with a fused four-membered ring could not be produced. One example in Table I therein shows the formation of an indolone by intramolecular condensation of an N-methyl-N-(2-ethoxycarbonylpropanoyl)-2-iodoanilide. In an adaptation of this method, Piers et al., J. Org. Chem. 1990, 55, 3454-3455, have disclosed a five -membered ring annulation method based on Pd(0)-catalyzed intramolecular coupling of a vinyl iodide function with an enolate anion function; in this method, the enolate anion was in a saturated five- or si
REFERENCES:
patent: 5015639 (1991-05-01), Berger et al.
Ciufolini et al., Tetrahedron Letters 1987, vol. 28 No. 2, 171-174.
Ciufolini et al., J. Org. Chem. [Communications] 1988, 53, 4149-4151.
Piers et al., J. Org. Chem. 1990, 55, 3454-3455.
Negishi et al., J. Am. Chem. Soc., 1989, 111, 8018-8020.
Semmelhack et al., J. Am. Chem. Soc., 1975, 97:9, 2507-2516.
Scott et al., Acc. Chem. Res., 1988, 21, 47-54.
Berger Joel G.
Chang Wei K.
Kozlowski Joseph A.
Zhou Guowei
Blasdale John H. C.
Mazer Edward H.
Nelson James R.
Raymond Richard L.
Schering Corportion
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