2 cyclo(alkyl and alkenyl) phenyl-alkenylyl heteroaryl compounds

Details 2 cyclo(alkyl and alkenyl) phenyl-alkenylyl heteroaryl compounds 2 cyclo(alkyl and alkenyl) phenyl-alkenylyl heteroaryl compounds

1997-11-20

1999-10-05

Shah, Mukund J.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514399, 514400, 514403, 514406, 5483097, 5483101, 5483355, 5483361, 5483411, 5483421, 5483625, 5483751, 5483761, C07D23118, C07D23156, C07D23366, A61K 31415

Patent

active

059624922

ABSTRACT:
Compounds of general formula (1) ##STR1## are described wherein Y is a halogen atom or a group --OR.sup.1, wherein R.sup.1 is an optionally substituted alkyl group; X is --O--, --S--, or --N(R.sup.6), wherein R.sup.6 is a hydrogen atom or an optionally substituted alkyl group; R.sup.2 is an optionally substituted cycloalkyl or cycloalkenyl group; R.sup.3 and R.sup.4, which may be the same or different, is each a hydrogen atom or an optionally substituted alkyl, --CO.sub.2 R.sup.7 (wherein R.sup.7 is a hydrogen atom, am optionally substituted alkyl, aralkyl, aryl, aryloxyalkyl, alkanoyloxyalkyl or aroyloxyalkyl group), --CONR.sup.8 R.sup.9 (where R.sup.8 and R.sup.9, which may be the same or different, is as defined for R.sup.7), --CSNR.sup.8 R.sup.9, --CN or --CH.sub.2 CN group; Z is --(CH.sub.2).sub.n -- where n is zero or an integer 1, 2 or 3; R.sup.5 is an optionally substituted monocyclic or bicyclic aryl group optionally containing one oremore heteroatoms selected from oxygen, sulphur or nitrogen atoms; and the salts, solvates, hydrates, prodrugs and N-oxides thereof. Compounds according to the invention are potent and selective phosphodiesterase type IV inhibitors and are useful in the prophylaxis and treatment of diseases such as asthma where an unwanted inflammatory response or muscular spasm is present.

REFERENCES:
patent: 3947467 (1976-03-01), Verge et al.
patent: 4012495 (1977-03-01), Schmiechen et al.
patent: 4015017 (1977-03-01), Gazave
patent: 4153713 (1979-05-01), Huth et al.
patent: 4193926 (1989-03-01), Schmiechen et al.
patent: 4303649 (1981-12-01), Jones
patent: 4694009 (1987-09-01), Hubele et al.
patent: 4788195 (1988-11-01), Torley et al.
patent: 4792561 (1988-12-01), Walker et al.
patent: 4876252 (1989-10-01), Torley et al.
patent: 4897396 (1990-01-01), Hubele
patent: 4921862 (1990-05-01), Walker et al.
patent: 4966622 (1990-10-01), Rempfler et al.
patent: 4971959 (1990-11-01), Hawkins
patent: 4987132 (1991-01-01), Mase et al.
patent: 5124455 (1992-06-01), Lombardo
patent: 5128358 (1992-07-01), Saccomano et al.
patent: 5159078 (1992-10-01), Rempfler et al.
patent: 5164372 (1992-11-01), Matsuo et al.
patent: 5175167 (1992-12-01), Zipperer et al.
patent: 5177085 (1993-01-01), Naef
patent: 5236918 (1993-08-01), Amschler et al.
patent: 5274002 (1993-12-01), Hawkins
patent: 5298511 (1994-03-01), Waterson
patent: 5326898 (1994-07-01), Chandraratna
patent: 5340827 (1994-08-01), Beeley et al.
patent: 5491147 (1996-02-01), Boyd et al.
patent: 5521184 (1996-05-01), Zimmermann
patent: 5550137 (1996-08-01), Beeley et al.
patent: 5580888 (1996-12-01), Warrellow et al.
patent: 5593997 (1997-01-01), Dow et al.
patent: 5608070 (1997-03-01), Alexander et al.
patent: 5622977 (1997-04-01), Warrellow et al.
patent: 5633257 (1997-05-01), Warrellow et al.
patent: 5674880 (1997-10-01), Boyd et al.
patent: 5691376 (1997-11-01), Caggiano et al.
patent: 5693659 (1997-12-01), Head et al.
patent: 5698711 (1997-12-01), Palfreyman
patent: 5716967 (1998-02-01), Kleinman
patent: 5723460 (1998-03-01), Warrellow et al.
patent: 5728708 (1998-03-01), Zimmermann
patent: 5739144 (1998-04-01), Warrellow et al.
patent: 5753663 (1998-05-01), Flippin et al.
patent: 5776958 (1998-07-01), Warrellow et al.
patent: 5780477 (1998-07-01), Head et al.
patent: 5780478 (1998-07-01), Alexander et al.
patent: 5786354 (1998-07-01), Warrellow et al.
patent: 5798373 (1998-08-01), Warrellow
patent: 5849770 (1998-12-01), Head et al.
patent: 5851784 (1998-12-01), Owens et al.
patent: 5859034 (1999-01-01), Warrellow et al.
patent: 5866593 (1999-02-01), Warrellow et al.
Ames, D.E. et al., "Some Dipyridylalkanes", J. Chem. Soc., 1962, 1475-1481.
Barton, D. et al., "A useful synthesis of pyrroles from nitroolefins", Tetrahedron, 1990, 46(21), 7587-7598 (HCAPLUS 1991:163917, 2 pages).
Fitzgerald, J.J. et al., "Reaction of benzocyclobutene oxides with nitriles: synthesis of hypecumine and other 3-substituted isoquinolines", Tetrahedron Lett., 1994, 35(49), 9191-9194 (HCAPLUS 1995:272292, 2 pages).
Hanna, M.M. et al., "Syntheis and antimicrobial activity of some substituted 3-aryl-5-benzylidene-2-phenyl-4-imidazolone derivatives", Bull. Fac. Pharm., 1994, 32(3), 353-359 (HCAPLUS 1996:586501, 2 pages).
Nanjo et al., "Preparation of 2-anilinopyrimidines as agricultural fungicides", Chem. Abstr., 1992, 116(21), No. 116:209703q.
Tollari, S. et al., "Intramolecular amination of olefins. Synthesis of 2-substituted-4-quinolones from 2-nitrochalcones catalyzed by ruthenium", J. Chem. Soc., 1994, 15, 1741-1742 (HCAPLUS 1994:605194, 2 pages).
Yamato, M. et al., "Chemical structure and sweet taste of isocoumarin and related compounds. VI", Chem. Pharm. Bull., 1975, 23(12), 3101-3105 (HCAPLUS 1976:99154, 2 pages).
Chemical Abstracts, Registry No. 2732-15-2, 1 page, 1965.
Chemical Abstracts, Registry No. 4593-13-9, 1 page, 1966.
Bortolus et al., "cis-trans Isomerization of azastilbenes photosensitized by biacetyl", Mol. Photochem., 1970, 2(4), 311-321, CAPLUS accession No. 1971-434722, 2 pages.
Kaiser et al., "Selective metalations of methylated pyridines and quinolines", J. Org. Chem., 1973, 38(1), 71-75, CAPLUS accession No. 1973-71853, 2 pages.
Pickett, W.C. et al., "Modulation of Eicosanoid Biosynthesis by Novel Pyridinylpyrimidines", Ann. N.Y. Acad. Sci., 1994, 744, 299-305.
Spada, A.P. et al., "Small Molecule Inhibitors of Tyrosine Kinase Activity", Exp. Opin. Ther. Patents, 1995, 5(8), 805-817.
Yamaguchi, H., "Guanidinobenzene derivatives as anticoagulants", Chem. Absts., 1989, 110, 655 (Abstract No. 94706z).
Zimmermann, J. et al., "Phenylamino-Pyrimidine (PAP) Derivatives: A New Class of Potent and Selective Inhibitors of Protein Kinase C (PKC)", Arch. Pharm., 1996, 329(7), 371-376.
Zimmermann, J. et al., "Phenylamino-Pyrimidine (PAP)--Derivatives: A New Class of Potent and Highly Selective PDGF-Receptor Autophosphorylation Inhibitors", Bioorg. Med. Chem. Lett., 1996, 6(11), 1221-1226.
Zimmerman, J. et al., "Potent and Selective Inhibitors of the ABL-Kinase Phenylamino-Pyrimidine (PAP) Derivatives", Biorg. Med. Chem. Lett., 1997, 7(2), 187-192.
Kefalas, P. et al., "Signalling by the p60.sup.c-src Family of Protein-Tyrosine Kinases", Int. J. Biochem. Cell Biol., 1995, 27(6), 551-563.
Chatterjee, A. et al., "Total Synthesis of Ring-C Aromatic 18-Nor Steroid", Tetrahedron, 1980, 36, 2513-2519.
Clayton, S.E. et al., "Direct Aromatic tert-Butylation during the Synthesis of Thiochroman-4-ones", Tetrahedron, 1993, 49(4), 939-946.
Collins, R.F. et al., "The Chemotherapy of Schistosomiasis. Part IV. Some Ethers of 4-Amino-2-methoxyphenol", J. Chem. Soc., 1961, 1863-1879.
Degani, I. et al., "Cationi etero-aromatici Nota VI--Sintesi di alcuni derivati del perclorato di tiacromilio", Boll. Sci. Fac. Chim. Ind. Bologna, 1966, 24(2-3), 75-91 (English Summary Only).
Geissler et al., "Biochemical and Biological Activity of a Novel Class of Tyrosine Protein Kinase Inhibitors", J. Biol. Chem., 1990, 265(36), 22255-22261.
Griffin, R.W. et al., "1-Methyl-7-halo-2-naphthalenecarboxylic Acid Derivatives", J. Organic Chem., 1964, 29(8), 2109-2116.
Gupta, A.S. et al., "Friedel-Crafts Condensation of Ethyl Allylmalonate with Anisole", Tetrahedron, 1967, 23, 2481-2490.
Hart et al., "Alkylation of Phenol with a Homoallylic Halide", J. Am. Chem. Soc., 1963, 85, 3269-3273.
Johnson et al., "Identification of Retinoic Acid Receptor .beta. Subtype Specific Agonists", J. Med. Chem., 1996, 39(26), 5027-5030.
Lehmann, J. et al., "Lactones; XIII. Grignard Reaction Followed by Phase-Transfer Oxidation: A Convenient Synthesis of .gamma.,.gamma.-Distributed .gamma.-Butyrolactones from .gamma.-Butyrolactone", Synthesis, 1987, 1064-1067 (English abstract only).
Meyers, A.I. et al., "The Synthesis of 2-Pyridones from Cyclic Cyano Ketones. A New Aromatization Procedure for Dihydro-2-pyridones", J. Org. Chem., 1964, 29, 1435-1438.
Ashton, "Selective Type IV Phosphodiesterase Inhibitors as Antiasthmatic Agents. The Syntheses and Biological Activities of 3-(Cyclopentyloxy)-4-methyoxybenzamides and Analogues", J. Med. Chem., 1994, 37, 1696-1703.
Beavo & Reifsnyder, "Pri

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