# US 4,396,626 A · Cyclic compounds and their use

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- Number: US 4,396,626 A
- Document ID: US4396626A
- Status: Granted
- Kind: A
- Application number: 06/306,534
- Filed: 1981-09-28
- Granted: 1983-08-02
- Earliest claimed: 1980-10-09
- Assignees: Beecham Group Limited
- Inventors: Robert W. Ward; Alexander C. Goudie
- Web page: https://patentgrep.com/patent/US4396626A

## CPC

- C07D 207/333: Radicals substituted by oxygen or sulfur atoms
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07D 207/337: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 207/34: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Compounds of the formula (I): ##STR1## and pharmaceutically acceptable salts and pro-drugs thereof, wherein: Ar is a phenyl group optionally substituted by one or two moieties selected from halogen, C.sub.1-4 alkyl, methoxy, methylthio or trifluoromethyl, or a 2-thienyl group or N-methyl-2-pyrryl group optionally substituted by one or two C.sub.1-4 alkyl groups; R is hydrogen or methyl; and n is 0 or 1 having useful anti-inflammatory and/or analgesic activity, pharmaceutical compositions containing them, and processes for their preparation.

## Claims

### Claim 1

A compound of the formula (I): ##STR27## or a pharmaceutically acceptable salt or a pro-drug thereof, wherein: Ar is phenyl unsubstituted or substituted by one or two moieties selected from halogen, C.sub.1-4 alkyl, methoxy, methylthio or trifluoromethyl;
R is hydrogen or methyl; and
n is 0 or 1.

### Claim 2 (depends on 1)

A compound according to claim 1 of the formula (VI): ##STR28## wherein the R.sub.1 and R.sub.2 are independently hydrogen, halogen, C.sub.1-4 alkyl, methylthio or trifluoromethyl, or a pharmaceutically acceptable salt thereof or a pro-drug thereof of the formula (VII), (VIII), (IX) or (X) ##STR29## wherein the variables are as defined in claim 1.

### Claim 3

5-p-Chlorobenzoyl-1-methyl-4-trifluoromethylpyrrole-2-acetic acid,
5-(3'-chlorobenzoyl)-1-methyl-4-trifluoromethylpyrrole-2-acetic acid,
5-(4'-methylbenzoyl)-1-methyl-4-trifluoromethylpyrrole acetic acid,
5-(4'-methoxybenzoyl)-1-methyl-4-trifluoromethylpyrrole acetic acid,
5-(3'-trifluoromethylbenzoyl)-1-methyl-4-trifluoromethylpyrrole acetic acid,
4-[5'-(4"-chlorobenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyrryl]but-1-ene,
4-[5'-(3"-chlorobenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyrryl]but-1-ene,
4-[5'-(4"-methylbenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyrryl]but-1-ene,
4-[5'-(4"-methoxybenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyrryl]but-1-ene,
4-[5'-(3"-trifluoromethylbenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyrryl]bu t-1-ene,
4-[5'-(4"-chlorobenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyroyl]butan-2-one
4-[5'-(3"-chlorobenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyroyl]butan-2-one
4-[5'-(4"-methylbenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyroyl]butan-2-one
4-[5'-(4"-methoxybenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyroyl]butan-2-on e,
4-[5'-(3"-trifluoromethylbenzoyl)-1'-methyl-4'-trifluoromethyl-2'-pyroyl]bu tan-2-one,
ethyl 5-(4'-methylbenzoyl)-1-methyl-4-trifluoromethylpyrrole-2-acetate,
ethyl 5-(4'-methoxybenzoyl)-1-methyl-4-trifluoromethylpyrrole-2-acetate or
ethyl 5-(3'-trifluoromethylbenzoyl)-1-methyl-4-trifluoromethylpyrrole-2-acetate

### Claim 4 (depends on 1)

A prodrug of a compound of the formula (I) according to claim 1, wherein the CO.sub.2 H group of the compound of the formula (I) is replaced by an in vivo hydrolysable ester or amide group, a CHO or CH.sub.2 OH group or by a group selected from those of sub-formulae (a)-(k):
--CH.sub.2 --CO--CH.sub.3 (a)
--CH.sub.2 --CHOH--CH.sub.3 (b)
--CHOH--CHOH--CH.sub.3 (c)
--CHOH--CO--CH.sub.3 (d)
--CH.sub.2 --CH(OCOR.sub.6)--CH.sub.3 (e)
--CH.dbd.C(OR.sub.7)--CH.sub.3 (f)
--CH--C(OR.sub.7).dbd.CH.sub.2 (g)
--CH.sub.2 --C(OR.sub.8)OR.sub.9 --CH.sub.3 (h)
--CH.sub.2 --C(OCOR.sub.10).dbd.CH.sub.2 (i)
--CH.dbd.C(OCOR.sub.10)--CH.sub.3 (j)
--CH.sub.2 --CH.dbd.CH.sub.2 (k)
wherein R.sub.6 is phenyl, substituted phenyl or C.sub.1-4 alkyl optionally substituted by optionally substituted phenyl or amino; R.sub.7 is a C.sub.1-4 alkyl group; R.sub.8 and R.sub.9 are each C.sub.1-4 alkyl groups or are joined to represent a CH.sub.2 CH.sub.2 or CH.sub.2 CH.sub.2 CH.sub.2 group; and R.sub.10 is a C.sub.1-4 alkyl group.

### Claim 5 (depends on 1)

An anti-inflammatory pharmaceutical composition comprising an anti-inflammatory effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt or a prodrug thereof and a pharmaceutically acceptable carrier.

### Claim 6 (depends on 1)

A method of treating inflammatory and/or painful conditions in mammals which comprises administering to the sufferer a therapeutically effective dose of a compound according to claim 1 or a pharmaceutically acceptable salt or a prodrug thereof.