Claims
- 1. A compound of the formula: ##STR30## or a pharmaceutically acceptable salt thereof, wherein X is O, S or NH;
- R and R.sup.1 are each independently selected from H and C.sub.1 -C.sub.4 alkyl or taken together represent C.sub.2 -C.sub.6 alkylene;
- R.sup.2 is H or C.sub.1 -C.sub.4 alkyl;
- R.sup.3 is
- (a) a 6-membered heterocyclic ring containing 1 N-hetero atom, said ring being linked to X by a ring carbon atom, optionally benzo-fused and optionally substituted, including in the benzo-fused portion, C.sub.1 -C.sub.6 alkyl, hydroxy, --OR.sup.5, halo, --S(O).sub.m R.sup.5, oxo, amino, --NHR.sup.5, --N(R.sup.5).sub.2, cyano, --CO.sub.2 R.sup.5, --CONH.sub.2, --CONHR.sup.5 or --CON(R.sup.5).sub.2, with the proviso that R.sup.3 is not an N-(C.sub.1 -C.sub.6 alkyl)pyridonyl group;
- (b), when X is NH, a group of the formula: ##STR31## (c), when X is NH, a group of the formula: ##STR32## R.sup.4 is phenyl substituted by a hydroxy group and optionally further substituted by 1 or 2 substitutents each independently selected from hydroxy, C.sub.1 -C.sub.6 alkyl, --OR.sup.5, halo, cyano and nitro;
- R.sup.5 is C.sub.1 -C.sub.6 alkyl;
- R.sup.6 is --OR.sup.5, --NHR.sup.5, --N(R.sup.5).sub.2, --SR.sup.5 or --NHR.sup.9 ;
- R.sup.7 is cyano;
- R.sup.8 is --OR.sup.5, --NHR.sup.5, --N(R.sup.5).sub.2, or --NHR.sup.9 ;
- R.sup.9 is phenyl optionally substituted by C.sub.1 -C.sub.6 alkyl, hydroxy, --OR.sup.5, halo, cyano or nitro; and
- m is 0, 1 or 2.
- 2. A compound as claimed in claim 1 wherein
- X is O or NH;
- R, R.sup.1 and R.sup.2 are each C.sub.1 -C.sub.4 alkyl;
- R.sup.3 is (a) a 6-membered heterocyclic ring containing 1 N hetero-atom, said ring being optionally benzo-fused and optionally substituted, including in the benzo-fused portion, by C.sub.1 -C.sub.4 alkyl, hydroxy, halo or oxo,
- (b) is a group of the formula: ##STR33## or (c) is a group of the formula: ##STR34## R.sup.4 is phenyl substituted by 1 or 2 hydroxy groups; R.sup.6 is --SR.sup.5 ; R.sup.8 is --OR.sup.5 ; and R.sup.5 and R.sup.7 are as defined in claim 1.
- 3. A compound as claimed in claim 2 wherein
- X is O;
- R, R.sup.1 and R.sup.2 are each methyl;
- R.sup.3 is 1,2-dihydro-2-oxo-1H-pyridin-4-yl, 1,2-dihydro-5,6-dimethyl-2-oxo-1H-pyridin-4-yl, 3,4-dioxo-2-ethoxycyclobut-1-en-1-yl or -cyano-2-methylisothioureido;
- and R.sup.4 is 2-hydroxyphenyl, 3-hydroxyphenyl, 4-hydroxyphenyl or 3,4-dihydroxyphenyl.
- 4. A compound as claimed in claim 3 wherein R.sup.3 is 1,2-dihydro-2-oxo-1H-pyridin-4-yl; and R.sup.4 is 3-hydroxyphenyl or 4-hydroxyphenyl.
- 5. A compound as claimed in claim 1 of the formula: ##STR35## where X, R, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as defined in claim 1.
- 6. A pharmaceutical composition comprising a compound of the formula (I), or a pharmaceutically acceptable salt thereof, as claimed in claim 1, together with a pharmaceutically acceptable diluent or carrier.
- 7. A method of treating a disease associated with the altered tone and/or motility of smooth muscle, comprising administering to a person in need of such treatment an effective amount of a compound of formula (I) as defined in claim 1, or a pharmaceutically acceptable salt or composition thereof.
- 8. A method as claimed in claim 7 where the disease is chronic obstructive airways disease, asthma, urinary incontinence, irritable bowel syndrome, diverticular disease, oesophageal achalasia or hypertension.
- 9. A compound of the formula: ##STR36## wherein X is O, S or NH;
- R and R.sup.1 are each independently selected from H and C.sub.1 -C.sub.4 alkyl or taken together represent C.sub.2 -C.sub.6 alkylene;
- R.sup.2 is H or C.sub.1 -C.sub.4 alkyl;
- R.sup.3 is
- (a) a 6-membered heterocyclic ring containing 1 N-hetero atom, said ring being linked to X by a ring carbon atom, optionally benzo-fused and optionally substituted, including in the benzo-fused portion, C.sub.1 -C.sub.6 alkyl, hydroxy, --OR.sup.5, halo, --S(O).sub.m R.sup.5, oxo, amino, --NHR.sup.5, --N(R.sup.5).sub.2, cyano, --CO.sub.2 R.sup.5, --CONH.sub.2, --CONHR.sup.5 or --CON(R.sup.5).sub.2, with the proviso that R.sup.3 is not an N-(C.sub.1 -C.sub.6 alkyl)pyridonyl group;
- (b), when X is NH, a group of the formula: ##STR37## (c), when X is NH, a group of the formula: ##STR38## R.sup.5 is C.sub.1 -C.sub.6 alkyl; R.sup.5 is --OR.sup.5, --NHR.sup.5, --N(R.sup.5).sub.2, --SR.sup.5 or --NHR.sup.9 ;
- R.sup.7 is cyano;
- R.sup.8 is --OR.sup.5, --NHR.sup.5, --N(R.sup.5).sub.2, or --NHR.sup.9 ;
- R.sup.9 is phenyl optionally substituted by C.sub.1 -C.sub.6 alkyl, hydroxy, --OR.sup.5, halo, cyano or nitro;
- R.sup.10 is phenyl substituted by a protected hydroxy group and optionally further substituted by 1 or 2 substituents each independently selected from a protected hydroxy group, hydroxy, C.sub.1 -C.sub.6 alkyl, --OR.sup.5, halo, cyano and nitro;
- R.sup.10b is phenyl substituted by a tri(C.sub.1 -C.sub.4 alkyl)silyloxy group and optionally further substituted by 1 or 2 substituents each independently selected form tri(C.sub.1 -C.sub.4 alkyl)silyloxy, hydroxy, C.sub.1 -C.sub.6 alkyl, --OR.sup.5, halo, cyano and nitro; and X, R, R.sup.1, R.sup.2, R.sup.3, and R.sup.5 are as defined in claim 1; and m is 0, 1 or 2.
- 10. A compound of the formula (VIA) as claimed in claim 9 wherein the tri(C.sub.1 -C.sub.4 alkyl)silyloxy group in the definition of R.sup.10b is tert-butyldimethylsilyloxy, or a compound of the formula (II) as claimed in claim 9 wherein the protected hydroxy group in the definition of R.sup.10 is C.sub.1 -C.sub.4 alkoxy or tri(C.sub.1 -C.sub.4 alkyl)silyloxy.
- 11. A compound of the formula (II) as claimed in claim 10 wherein the protected hydroxy group in the definition of R.sup.10 is methoxy or tert-butyldimethylsilyloxy.
Priority Claims (1)
Number |
Date |
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9316111 |
Aug 1993 |
GBX |
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Parent Case Info
This is a divisional of application Ser. No. 08/591,500, filed Jul. 8, 1996, now U.S. Pat. No. 5,912,244 which is a National Stage Filing under 35 U.S.C. .sctn.371 based on PCT/EP94/02387 which was filed internationally on Jul. 18, 1994.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
4999371 |
Englert et al. |
Mar 1991 |
|
5112972 |
Gericke et al. |
May 1992 |
|
Foreign Referenced Citations (14)
Number |
Date |
Country |
0277611 |
Aug 1988 |
EPX |
0277612 |
Aug 1989 |
EPX |
0337179 |
Oct 1989 |
EPX |
0340718 |
Nov 1989 |
EPX |
0346724 |
Dec 1989 |
EPX |
0351720 |
Jan 1990 |
EPX |
0355565 |
Feb 1990 |
EPX |
0363883 |
Apr 1990 |
EPX |
0400430 |
Dec 1990 |
EPX |
0450415 |
Oct 1991 |
EPX |
0547523 |
Jun 1993 |
EPX |
0552679 |
Jul 1993 |
EPX |
0331189 |
Jan 1989 |
IEX |
2242628 |
Oct 1991 |
GBX |
Divisions (1)
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Number |
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Parent |
591500 |
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