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US 5,965,576 AGranted
Cyclic amide derivatives for treating asthma
AssigneeZeneca Limited
InventorsAshokkumar Bhikkappa Shenvi, Robert Toms Jacobs, Scott Carson Miller, Cyrus John Ohnmacht, Jr., Chris Allan Veale
Life of this patent
Estimating the term…
Abstract
Compounds of formula I ##STR1## wherein Q.sup.1, Q.sup.2, Q.sup.3, and Q.sup.4 have any of the meanings given in the specification, their N-oxides, and their pharmaceutically acceptable salts are nonpeptide antagonists of neurokinin A and useful for the treatment of asthma, etc. Also disclosed are pharmaceutical compositions, processes for preparing the compounds of formula I and intermediates.
Claims8
A compound of the following formula:
- wherein:
- X.sup.j is (1-6C)alkyl, --CH.sub.2 OR.sup.ja, --CH.sub.2 SR.sup.ja, --CH.sub.2 S(O)R.sup.jg, --CH.sub.2 S(O).sub.2 R.sup.jg, --COR.sup.ja, --COOR.sup.ja, --C(.dbd.J.sup.ja)NR.sup.jb R.sup.jc, --C(R.sup.ja) (OR.sup.jd) (OR.sup.je), --CH.sub.2 N(R.sup.ja)C(.dbd.J.sup.ja)R.sup.jf, --CH.sub.2 (R.sup.ja)COOR.sup.jg or --CH.sub.2 N(R.sup.ja)C(.dbd.J.sup.ja)NR.sup.jb R.sup.jc ;
- B.sup.j is a direct bond and L.sup.j is a hydrocarbon chain in which the 1-position is bound to B.sup.j and L.sup.j is selected from trimethylene, tetramethylene, cis-1-butenylene and cis,cis-butadienylene;
- or B.sup.j is N(R.sup.jh) and L.sup.j is a hydrocarbon chain selected from ethylene, trimethylene and cis-vinylene;
- or B.sup.j is N and L.sup.j is a hydrocarbon chain in which the 1-position is bound to B.sup.j and L.sup.j is cis,cis-prop-2-en-1-ylidin-3-yl;
- J.sup.j and J.sup.ja are independently oxygen or sulfur;
- R.sup.ja, R.sup.jf and R.sup.jh are independently hydrogen or (1-6C)alkyl;
- R.sup.jb and R.sup.jc are independently hydrogen or (1-6C)alkyl;
- or the radical NR.sup.jb R.sup.jc is pyrrolidino, piperidino, morpholino, thiomorpholino (or its S-oxide) or piperazinyl (which piperazinyl may bear a (1-3C)alkyl substituent at the 4-position);
- R.sup.jd and R.sup.je are independently (1-3C)alkyl or together form a divalent hydrocarbon chain selected from ethylene and trimethylene;
- R.sup.jg is (1-6C)alkyl;
- J is oxygen or sulfur;
- M.sup.1 is CR.sup.F or N;
- R.sup.A is hydrogen or (1-3C)alkyl;
- R.sup.B, R.sup.C, R.sup.D, and R.sup.E are each hydrogen, or one or more of R.sup.B, R.sup.C, R.sup.D, and R.sup.E is a substituent independently selected from halo, trifluoromethyl, hydroxy, (1-3C)alkoxy, (1-3C)alkyl, (1-3C)alkylthio, (1-3C)alkylsulfinyl and (1-3C)alkylsulfonyl, and the others of R.sup.B, R.sup.C, R.sup.D, and R.sup.E are each hydrogen;
- or two adjacent R.sup.B, R.sup.C, R.sup.D, and R.sup.E form a methylenedioxy substituent and the others of R.sup.B, R.sup.C, R.sup.D, and R.sup.E are hydrogen;
- R.sup.F is hydrogen, hydroxy, (1-3C)alkoxy or (1-3C)alkyl;
- Q.sup.3 is hydrogen or (1-3C)alkyl;
- and
- Q.sup.4 is phenyl which may bear one or two substituents independently selected from halo, trifluoromethyl, hydroxy, (1-3C)alkoxy, (1-3C)alkyl, methylenedioxy, (1-3C)alkoxycarbonyl and (1-3C)alkylthio;
- or Q.sup.4 is thienyl, imidazolyl, benzo[b]thiophenyl or naphthyl any of which may bear a halo substituent;
- or Q.sup.4 is biphenylyl;
- or Q.sup.4 is carbon-linked indolyl which may bear a benzyl substituent at the 1-position;
- or the N-oxide of a piperidino nitrogen indicated by .DELTA.;
- or a pharmaceutically acceptable salt thereof;
- or a quaternary ammonium salt thereof in which the piperidino nitrogen indicated by .DELTA. is a quadricovalent ammonium nitrogen wherein the fourth radical on the nitrogen R.sup.1 is (1-4C)alkyl or benzyl and the associated counterion A is a pharmaceutically acceptable anion.
23 more elements
Dependencies are inferred from the claim text.