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Analgesic n-(2-aminocycloaliphatic)benzamides

Assignee: Pharmacia and Upjohn Co
•
Filing: 1976-11-12
•
Granted: 1978-07-04
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Expires: 1996-11-12
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Abstract

Abstract Cis- and trans-N-(2-aminocycloaliphatic)benzamide compounds of the formula ##STR1## E.G., N-methyl-N[2-(N-pyrrolidinyl)cyclohexyl[3,4-dichlorobenzamide, and their pharmaceutically acceptable salts, have been found to have potent analgesic activity, and compositions containing these compounds useful in pharmaceutical dosage unit form for alleviating pain in warm blooded animals, as well as methods for alleviating pain in animals with these compositions. Processes for preparing the compounds are also disclosed.

Inventors

  • 👤 Jacob Szmuszkovicz

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-08 21:52
CPC Classifications
C; C07; C07D; C07D295/00; C07D295/04; C07D295/12; C07D295/135; A; A61; A61P; A61P25/00

Claims Analysis

Total Claims: 23
Claim 1
Independent Claim 266 words
A compound of the formula ##STR64## wherein the wavy line (˜) at the 1-position of the cycloaliphatic ring denotes trans-stereoconfiguration of the 1-position substituent with respect to the substituent in position 2 of the same cycloaliphatic ring; n is 1 to 8; R is hydrogen or C 1 to C 3 -alkyl; R 1 and R 2 , taken separately, are hydrogen, C 1 to C 3 -alkyl or when R 1 is hydrogen or C 1 to C 3 -alkyl, R 2 is C 1 to C 6 -alkyl, CH 2 CF 3 , C 2 to C 5 -hydroxyalkyl, phenyl-C 2 to C 3 -alkyl, C 3 to C 6 -cycloalkyl, C 3 to C 4 -cycloalkylmethyl, and Q is 1-naphthyl, 2-naphthyl or the radical ##STR65## wherein each of X, Y and Z is hydrogen, a halogen having an atomic number of from 9 to 35, nitro, methanesulfonyl, C 1 to C 3 -alkanoyl, trifluoromethyl, C 1 to C 3 -alkyl, benzoyl or phenyl, and at least one of X, Y and Z is a substituent other than hydrogen, and when one of X, Y and Z is phenyl, the remaining X, Y or Z moieties are hydrogen, and when R is hydrogen, and n is 2 and Q is ##STR66## which is monosubstituted X and Y are hydrogen and Z cannot be methanesulfonyl, or 3-chloro; and R must be C 1 to C 3 -alkyl when n is 1, and when one of X, Y and Z is methanesulfonyl, R is C 1 to C 3 -alkyl and the pharmaceutically acceptable salts thereof.
Claim 2
Dependent Claim 266 words
A compound of the formula ##STR64## wherein the wavy line (˜) at the 1-position of the cycloaliphatic ring denotes trans-stereoconfiguration of the 1-position substituent with respect to the substituent in position 2 of the same cycloaliphatic ring; n is 1 to 8; R is hydrogen or C 1 to C 3 -alkyl; R 1 and R 2 , taken separately, are hydrogen, C 1 to C 3 -alkyl or when R 1 is hydrogen or C 1 to C 3 -alkyl, R 2 is C 1 to C 6 -alkyl, CH 2 CF 3 , C 2 to C 5 -hydroxyalkyl, phenyl-C 2 to C 3 -alkyl, C 3 to C 6 -cycloalkyl, C 3 to C 4 -cycloalkylmethyl, and Q is 1-naphthyl, 2-naphthyl or the radical ##STR65## wherein each of X, Y and Z is hydrogen, a halogen having an atomic number of from 9 to 35, nitro, methanesulfonyl, C 1 to C 3 -alkanoyl, trifluoromethyl, C 1 to C 3 -alkyl, benzoyl or phenyl, and at least one of X, Y and Z is a substituent other than hydrogen, and when one of X, Y and Z is phenyl, the remaining X, Y or Z moieties are hydrogen, and when R is hydrogen, and n is 2 and Q is ##STR66## which is monosubstituted X and Y are hydrogen and Z cannot be methanesulfonyl, or 3-chloro; and R must be C 1 to C 3 -alkyl when n is 1, and when one of X, Y and Z is methanesulfonyl, R is C 1 to C 3 -alkyl and the pharmaceutically acceptable salts thereof.
Claim 3
Dependent Claim 62 words
A compound according to claim 1 wherein n is 1 to 4; R is C 1 to C 3 -alkyl; R 1 and R 2 are each C 1 to C 3 -alkyl; and Q is ##STR67## wherein X and Y are halogens having an atomic number of from 9 to 35 and Z is hydrogen, and the pharmaceutically acceptable salts thereof.
Claim 4
Dependent Claim 17 words
A compound according to claim 2 wherein the compound is trans-N-methyl-N-[2-(N',N'-dimethylamino)cyclopentyl]-3,4-dichlorobenzamide, and the pharmaceutically acceptable salts thereof.
Claim 5
Dependent Claim 40 words
A compound according to claim 1 wherein n is 2; R is C 1 to C 3 -alkyl, R 1 and R 2 are each C 1 to C 3 -alkyl, Q is 2-naphthyl, and the pharmaceutically acceptable salts thereof.
Claim 6
Dependent Claim 16 words
A compound according to claim 4 wherein the compound is trans-N-[2-(N',N'-dimethylamino)cyclohexyl]-N-methyl-2-naphthamide, and its pharmaceutically acceptable salts.
Claim 7
Dependent Claim 47 words
A compound according to claim 1 wherein n is 1 to 4; R is C 1 to C 3 -alkyl; R 1 and R 2 are each C 1 to C 3 -alkyl; and Q is ##STR68## wherein X is trifluoromethyl, and the pharmaceutically acceptable salts thereof.
Claim 8
Dependent Claim 18 words
A compound according to claim 6 wherein the compound is trans-N-methyl-N-[2-(N',N'-dimethylamino)cyclohexyl]-4-α,α,.alpha.-trifluoro p-toluamide and the pharmaceutically acceptable salts thereof.
Claim 9
Dependent Claim 17 words
A compound according to claim 6 wherein the compound is trans-N-methyl-N-[2-(N',N'-dimethylamino)cyclooctyl]-4-trifluoromethylbenzamide, and the pharmaceutically acceptable salts thereof.
Claim 10
Dependent Claim 46 words
A compound according to claim 1 wherein n is 2; R is hydrogen; R 1 and R 2 are each C 1 to C 3 -alkyl; and Q is ##STR69## wherein X is nitro and Y and Z are hydrogen, and the pharmaceutically acceptable salts thereof.
Claim 11
Dependent Claim 17 words
A compound according to claim 9 wherein the compound is trans-N-[2-(N',N'-dimethylamino)cyclohexyl]-4-nitrobenzamide, and the pharmaceutically acceptable salts thereof.
Claim 12
Dependent Claim 56 words
A compound according to claim 1 wherein n is 2; R is C 1 to C 3 -alkyl; R 1 is C 1 to C 3 -alkyl; R 2 is C 3 to C 4 -cycloalkylmethyl; and Q is ##STR70## wherein X is trifluoromethyl and Y and Z are hydrogen, and the pharmaceutically acceptable salts thereof.
Claim 13
Dependent Claim 17 words
A compound according to claim 11 wherein the compound is trans-N-methyl-N-[2-(N'-methyl-N'-cyclobutylmethylamino)cyclohexyl]-4-trifluoromethylbenzamide, and the pharmaceutically acceptable salts thereof.
Claim 14
Dependent Claim 55 words
A compound of claim 1 wherein n is 2; R is C 1 to C 3 -alkyl; R 1 is C 1 to C 3 -alkyl; R 2 is C 3 to C 6 -(allylic)alkenyl; and Q is ##STR71## wherein X is trifluoromethyl and Y and Z are hydrogen, and the pharmaceutically acceptable salts thereof.
Claim 15
Dependent Claim 11 words
A compound according to claim 1 wherein the compound is trans-N-[2-(dimethylamino)cyclohexyl]-4-bromobenzamide.
Claim 16
Dependent Claim 7 words
N-methyl-N-[2-(N,N-dimethylamino)cyclohexyl]-3,4-dichlorobenzamide, and the pharmacologically acceptable salts thereof.
Claim 17
Dependent Claim 7 words
N-methyl-N-[2-(N,N-dimethylamino)cyclohexyl]-3,4-dichlorobenzamide, and the pharmacologically acceptable salts thereof.
Claim 18
Dependent Claim 50 words
A composition useful in pharmaceutical dosage unit form in an amount effective for alleviating pain in warm blooded animals which comprises a compound of Formula I in claim 1 in an amount ranging from about 0.5 to about 350 mg. per dosage unit in combination with a pharmaceutical acceptable carrier.
Claim 19
Dependent Claim 18 words
A composition according to claim 16 wherein the compound of formula I is a compound of claim 2.
Claim 20
Dependent Claim 18 words
A composition according to claim 17 wherein the compound of formula I is a compound of claim 3.
Claim 21
Dependent Claim 36 words
A method for alleviating pain in a warm blooded animal which comprises administering to the warm blooded animal suffering pain a compound of formula I in claim 1 in an amount effective to relieve the pain.
Claim 22
Dependent Claim 32 words
A method according to claim 19 wherein the compound of formula I in claim 1 is administered in an amount between about 0.5 to 350 mg. per dose in a pharmaceutical carrier.
Claim 23
Dependent Claim 63 words
A process which comprises reacting a 1,2-cycloaliphatic diamine of the formula ##STR72## wherein the ˜ symbol, n R, R 1 and R 2 are as defined in claim 1 with an aracyl imidazole of the formula ##STR73## wherein Q is as defined in claim 1 in an organic solvent for a time sufficient to form a compound of formula I in claim 1.

References Cited (Backward Citations)

US3499033A Cited
US3373195A Cited
US3510492A Cited
US3647804A Cited
US3847982A Cited
US3825595A Cited
US3975443A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1981-07-03 1982-01-02 1982-07-04 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1985-07-03 1986-01-02 1986-07-04 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1989-07-03 1990-01-02 1990-07-04 $7700.00 Window Closed / Lapsed

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