US4098904A
Expired / Lapsed
US
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Analgesic n-(2-aminocycloaliphatic)benzamides
Assignee: Pharmacia and Upjohn Co
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Filing: 1976-11-12
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Granted: 1978-07-04
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Expires: 1996-11-12
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 21:34
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.
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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 |