Back to results
US 5,182,289 AGranted
Heterobicyclic compounds having antiinflammatory activity
AssigneeSchering Corporation
InventorsPauline C. Ting, Margaret H. Sherlock, Wing C. Tom, James J. Kaminski
Life of this patent
Estimating the term…
Abstract
Heterobicyclic and heterocyclic intermediate compounds and their use in treating inflammation, hyperproliferative skin conditions such as psoriasis and allergy are disclosed.
Claims20
A compound of formula ##STR94## or a pharmaceutically acceptable salt or solvate thereof, wherein A is selected from ##STR95## the dotted lines represent optional double bonds, such that when the bond to X is a double bond, X is O or S;
- and
- when the bond to X is a single bond, X is --OR.sup.10 wherein R.sup.10 is alkyl or aralkyl wherein one and only one of the pair of dotted lines must be a double bond;
- T.sup.2 and T.sup.3 independently represent S, SO or SO.sub.2 ;
- m and n independently represent 0 or 1;
- R.sup.1 represents hydrogen, alkyl, aryl, aralkyl, or a 5- or 6-membered heterocyclic aromatic ring having from 1 to 3 heteroatoms in the ring, each heteroatom independently selected from NR.sup.6, O, S or N atoms wherein R.sup.6 is hydrogen or C.sub.1 to C.sub.4 alkyl;
- R.sup.2 and R.sup.3 independently represent
- hydrogen with the proviso at least one of R.sup.2 and R.sup.3 is not hydrogen;
- alkyl;
- cycloalkyl;
- halogen;
- haloalkyl;
- hydroxyalkyl;
- alkoxyalkyl;
- aryl;
- aralkyl;
- --COR.sup.7 wherein R.sup.7 is alkyl, aryl or aralkyl;
- and with the further proviso that when T.sup.2.sub.m or T.sup.3.sub.n is S, SO or SO.sub.2 that R.sup.2 or R.sup.3 is not hydrogen or halogen;
- --D--OCO--R.sup.4 wherein D represents an alkylene group having from 1 to 4 carbon atoms and R.sup.4 is alkyl, aryl or aralkyl;
- a C.sub.3 to C.sub.7 spirocarbocyclic ring whereby R.sup.2 and R.sup.3 are joined together;
- the rings represented by A, R.sup.1, aryl or aralkyl may each be optionally substituted by up to three Y substituents;
- wherein each Y substituent independently represents --OH, hydroxyalkyl, alkyl, halogen, --NO.sub.2, alkoxy, alkoxyalkyl, --CF.sub.3, --CN, cycloalkyl, alkynyloxy, alkenyloxy, --S(O).sub.p --R.sup.4 (wherein R.sup.4 is defined above and p is an integer from 0 to 2), --CO--R.sup.5 (wherein R.sup.5 represents --OH, --NH.sub.2, --NHR.sup.4, N(R.sup.4).sub.2 or --OR.sup.4 in which R.sup.4 is as defined above), --O--D--COR.sup.5 (wherein D is defined above and R.sup.5 is as defined above), --NH.sub.2, --NHR.sup.4, --N(R.sup.4).sub.2 (wherein R.sup.4 is as defined above) or --NHC(O)H
- with the proviso in formula I that if:
- X is oxygen;
- A is ##STR96## Y, if present is alkyl;
- at least one of R.sup.2 and R.sup.3 is alkyl or halogen;
- then
- R.sup.1 cannot be hydrogen.
24 more elements
A compound of the formula ##STR100## wherein ring A represents ##STR101## each Y.sup.1 independently represents hydrogen, chloro, fluoro, methoxy, methylthio, methylsulfinyl and methylsulfonyl;
- R.sup.2 and R.sup.3 are independently selected from methyl, ethyl and fluoro;
- and
- X is O or S.
A compound which is
- 1-(4-chlorophenyl)-1,3-dihydro-3,3-dimethyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3,3-dimethyl-1-[4-(methylsulfinyl)phenyl]-2H-pyrrolo[2,3-b]pyri din-2-one,
- 1,3-dihydro-3,3-dimethyl-1-[4-(methylsulfonyl)phenyl-2H-pyrrolo[2,3-b]pyrid in-2-one,
- 1,3-dihydro-3,3-dimethyl-1-phenyl-2H-pyrrolo[2,3-b]-pyridine-2-thione,
- 1,3-dihydro-1,3,3-trimethyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 5-bromo-1,3-dihydro-3,3-dimethyl-1-(4-chlorophenyl)-2H-pyrrolo[2,3-b]pyridi n-2-one,
- 1,3-dihydro-3-fluoro-3-methyl-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3,3-dimethyl-1-(1-methylethyl)-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3,3-dimethyl-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3,3-dimethyl-1[4-(1-methylethyl)phenyl]-2H-pyrrolo[2,3-b]pyridi n-2-one,
- 1-(3-chlorophenyl)-1,3-dihydro-3,3-dimethyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1-(3,4-dichlorophenyl)-1,3-dihydro-3,3-dimethyl-2H-pyrrolo[2,3-b]pyridin-2- one,
- 1,3-dihydro-3,3-dimethyl-1-(4-fluorophenyl)-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3,3-dimethyl-1-[4-(methylthio)phenyl]-2H-pyrrolo[2,3-b]pyridin- 2-one,
- 1,3-dihydro-3,3-dimethyl-1-[3-(trifluoromethyl)phenyl]-2H-pyrrolo[2,3-b]pyr idin-2-one,
- 1-(4-bromophenyl)-1,3-dihydro-3,3-dimethyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1-(2,4-dichlorophenyl)-1,3-dihydro-3,3-dimethyl-2H-pyrrolo[2,3-b]pyridin-2- one,
- 1. 3-dihydro-3,3-diethyl-1-phenyl-2H-pyrrolo[2,3-b]-pyridin-2-one,
- 1,3-dihydro-3,3-dimethyl-1-(2-methyl-3-chlorophenyl)-2H-pyrrolo[2,3-b]pyrid in-2-one,
- 1,3-dihydro-3,3-dimethyl-1-(4-methoxyphenyl)-2H-pyrrolo[2,3-b]pyridin-2-one
- 1-(2,4-difluorophenyl)-1,3-dihydro-3,3-dimethyl-2H-pyrrolo[2,3-b]pyridin-2- one,
- 1-(3,5-dichlorophenyl)-1,3-dihydro-3,3-dimethyl-2H-pyrrolo[2,3-b]pyridin-2- one,
- 1,3-dihydro-1-phenyl-3-(phenylthio)-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3-(phenylthio)-1-(3-trifluoromethylphenyl)-2H-pyrrolo[2,3-b]pyr idin-2-one,
- 1,3-dihydro-3-(phenylsulfinyl)-1-(3-trifluoromethylphenyl)-2H-pyrrolo[2,3-b ]pyridin-2-one,
- 1,3-dihydro-1-(methylethyl)-3-(phenylthio)-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-1-(4-(1-methylethyl)-phenyl)-3-(phenylthio)-2H-pyrrolo[2,3-b]py ridin-2-one,
- 2-methoxy-1-phenyl-3-(phenylthio)-1H-pyrrolo[2,3-b]pyridine,
- 1,3-dihydro-3-methyl-1-phenyl-3-(phenylthio)-2H-pyrrolo[2,3-b]pyridin-2-one
- 1. 3-dihydro-1-methyl-3-(phenylthio)-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-1-(3-chloro-2-methylphenyl)-3-(phenylthio)-2H-pyrrolo[2,3-b]pyr idin-2-one,
- 1,3-dihydro-3-(4-chlorophenylthio)-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3-(2-chlorophenylthio)-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3-(4-methoxyphenylthio)-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one
- 1,3-dihydro-3-(2-methoxyphenylthio)-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one
- 1,3-dihydro-3-(2-methylphenylthio)-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-1-methyl-3-(phenylsulfinyl)-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3-(2-hydroxyethylthio)-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3,3-(diphenylthio)-1-(phenylmethyl)-2H-pyrrolo[2,3-b]pyridin-2- one,
- 1,3-dihydro-1-(phenylmethyl)-3-(phenylthio)-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3-[2-(acetoxy)-ethylthio)-3-(1-oxoethyl)-1-phenyl-2H-pyrrolo[2, 3-b]pyridin-2-one,
- 1. 3-dihydro-3-[2-hydroxyethylthio]-3-(1-oxoethyl)-1-phenyl-2H-pyrrolo[2,3- b]pyridin-2-one,
- 1,3-dihydro-3-[2-(acetoxy)-ethylthio]-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-o ne,
- 1,3-dihydro-1-methyl-3-(phenylsulfonyl)-2H-pyrrolo[2,3-b]pyridin-2-one,
- 1,3-dihydro-3-methyl-3-(methylthio)-1-phenyl-2H-pyrrolo[2,3-b]pyridin-2-one
- 1,3-dihydro-1-(3-chlorophenyl)-3-(phenylthio)-2H-pyrrolo[2,3-b]pyridin-2-on e or
- 1,3-dihydro-1-(3,4-dichlorophenyl)-3-(phenylthio)2H-pyrrolo[2,3-b]pyridin-2 -one.
44 more elements
1 -(4-chlorophenyl)-1,3-dihydro-3,3-dimethyl-2H-pyrrolo[2,3-b]pyridin-2-one.
1,3-dihydro-3,3-dimethyl-1-(4-fluorophenyl)-2H-pyrrolo[2,3-b]pyridin-2- one.
1,3-dihydro-3,3-dimethyl-1-(4-methoxyphenyl)-2H-pyrrolo[2,3-b]pyridin-2-one
Dependencies are inferred from the claim text.