Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1998-12-16
2000-06-06
Kight, John
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
546 16, 544224, 544242, 544359, 544366, 544367, 544369, A61K 3144, C07D22100, C07D25100, C07D23900, C07D40300
Patent
active
060719281
DESCRIPTION:
BRIEF SUMMARY
This invention relates to a class of azacyclic compounds which are useful as tachykinin antagonists. More particularly, the compounds of the invention are spiro-substituted azacyclic derivatives.
International (PCT) patent specification no. WO 94/20500 (published Sep. 15, 1994) discloses spiroazacyclic derivatives as substance P antagonists. In particular, WO 94/20500 relates to spirocyclic piperidine derivatives containing a 1,8-diazaspiro[5.5]undecane core.
We have now found a further class of non-peptides which are potent antagonists of tachykinins, especially of substance P.
The present invention provides compounds of the formula (I): ##STR2## wherein R represents C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, which groups are optionally substituted by a group selected from hydroxy, C.sub.1-4 alkoxy or NR.sup.a R.sup.b, where R.sup.a and R.sup.b each independently represent hydrogen or C.sup.1-4 alkyl; optionally further substituted by one or both of the groups R.sup.4 and R.sup.5 ; C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, C.sub.1-6 alkoxy, fluoroC.sub.1-6 alkyl, fluoroC.sub.1-6 alkoxy, hydroxyC.sub.1-4 alkyl, C.sub.1-6 alkoxyC.sub.1-4 alkyl, C.sub.1-6 alkoxyC.sub.1-4 alkoxy, fluoroC.sub.1-6 alkoxyC.sub.1-4 alkyl, C.sub.2-6 alkenyloxy, C.sub.3-7 cycloalkoxy, C.sub.3-7 cycloalkylC.sub.1-4 alkoxy, phenoxy, benzyloxy, cyano, halogen, trimethylsilyl, nitro, NR.sup.a R.sup.h, SR.sup.a, SOR.sup.a, SO.sub.2 R.sup.a, OSO.sub.2 R.sup.a. COR.sup.a, CO.sub.2 R.sup.a, CONR.sup.a R.sup.b, SO.sub.2 NR.sup.a R.sup.b, or OC.sub.1-4 alkylNR.sup.a R.sup.b. where R.sup.a and R.sup.b each independently represent hydrogen, C.sub.1-4 alkyl or fluoroC.sub.1-4 alkyl; that there is formed a 5- or 6-membered saturated or unsaturated ring containing one or two atoms selected from nitrogen, oxygen and sulphur, which ring is optionally substituted by a group selected from C.sub.1-4 alkyl, CF.sub.3, .dbd.O or .dbd.S; C.sub.2-6 alkynyl, fluoroC.sub.1-6 alkyl, C.sub.1-6 alkoxy, fluoroC.sub.1-6 alkoxy, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, hydroxy, phenoxy, benzyloxy, trimethylsilyl, nitro, cyano, SR.sup.a, SOR.sup.a, SO.sub.2 R.sup.a, NR.sup.a R.sup.b, COR.sup.a, CO.sub.2 R.sup.a, CONR.sup.a R.sup.b, SO.sub.2 NR.sup.a R.sup.b, OC.sub.1-4 alkylNR.sup.a R.sup.b, NR.sup.a COR.sup.d, or C.sub.1-4 alkyl substituted by a C.sup.1-4 alkoxy, hydroxy, cyano or CO.sub.2 R.sup.a group, where R.sup.a and R.sup.b are as previously defined and R.sup.d is C.sub.1-6 alkyl, C.sub.1-6 alkoxy, fluoroC.sub.1-6 alkyl or phenyl; containing 1, 2, 3 or 4 heteroatoms, selected from nitrogen, oxygen and sulphur, which group is optionally substituted by one or two groups selected from C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.3-7 cycloalkyl, C.sub.3-7 cycloalkylC.sub.1-4 alkyl, trifluoromethyl, OCF.sub.3, NO.sub.2, CN, SR.sup.a, SOR.sup.a, SO.sub.2 R.sup.a, COR.sup.a, CO.sub.2 R.sup.a, phenyl, --(CH.sub.2).sub.r NR.sup.a R.sup.b, --(CH.sub.2).sub.r NR.sup.a COR.sup.b, --(CH.sub.2).sub.r CONR.sup.a R.sup.b, or CH.sub.2 C(O)R.sup.a, where R.sup.a and R.sup.b are each independently hydrogen or C.sub.1-4 alkyl and r is zero, 1 or 2; C.sub.1-4 alkoxyC.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl or C.sub.1-4 alkylNR.sup.a R.sup.b where R.sup.a and R.sup.b are each independently hydrogen or C.sub.1-4 alkyl, or together R.sup.4 and R.sup.5 represent an oxo group or when R.sup.4 and R.sup.5 are attached to the same carbon atom, they may be joined together to form a C.sub.3-5 cycloalkyl ring; selected from halogen, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, CF.sub.3, OCF.sub.3, NO.sub.2, CN, SR.sup.a, SOR.sup.a, SO.sub.2 R.sup.a, COR.sup.a, CO.sub.2 R.sup.a, (CH.sub.2).sub.r CONR.sup.a R.sup.b, (CH.sub.2).sub.r NR.sup.a R.sup.b or (CH.sub.2).sub.r NR.sup.a COR.sup.b, where R.sup.a and R.sup.b are independently hydrogen or C.sub.1-4 alkyl and r is zero, 1 or 2; 2 or 3 nitrogen atoms optionally substituted by .dbd.O or .dbd.S and optionally substituted by a group o
Curtis Neil Roy
Huscroft Ian Thomas
Kulagowski Janusz Jozef
Swain Christopher John
Kight John
Merck Sharp & Dohme Ltd.
Robinson Binta
Rose David L.
Thies J. Eric
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