US3979444A
Expired / Lapsed
US
⏱️ 0.0 years remaining
4-Arylcyclohexylamines
Assignee: Pharmacia and Upjohn Co
•
Filing: 1974-05-28
•
Granted: 1976-09-07
•
Expires: 1994-05-28
Abstract
Abstract The invention relates to novel 4-hydroxymethyl(acyloxymethyl and methyl)-4-arylcyclohexylamines embraced by the formula ##SPC1## Wherein Ar is an aromatic ring selected from the group consisting of phenyl and naphthyl, each of which has from zero through three substituents independently selected from the group consisting of fluorine, chlorine, bromine, lower alkyl of one through three carbon atoms, lower alkoxy of one through three carbon atoms, and lower alkylthio of one through three carbon atoms; Z is selected from the group consisting of hydrogen, hydroxy and lower acyloxy of one through four carbon atoms; ˜ is a generic expression denoting cis and trans stereoconfiguration and mixtures thereof, with the proviso that when the stereoconfiguration of the linkage connecting the cyclohexane ring and CH 2 Z is cis to the amino group, the linkage connecting the cyclohexane and Ar rings is trans, and vice versa; R 1 is selected from the group consisting of hydrogen and lower alkyl of one through three carbon atoms; R 2 is selected from the group consisting of hydrogen, lower alkyl of one through three carbon atoms, ##EQU1## WHEREIN N IS 2 THROUGH 5 AND Ar has the same meaning as above; R 1 and R 2 taken together with --N< is a saturated heterocyclic amino radical selected from the group consisting of unsubstituted and substituted pyrrolidino, piperidino, hexamethylenimino, morpholino and piperazino; and pharmacologically acceptable acid addition salts thereof. It also relates to intermediates and processes for the preparation of the aforesaid novel compounds (I) and novel derivatives thereof. The administration to humans and animals of the novel compounds (I) depresses their central nervous systems and lowers their blood pressures.
Inventors
- 👤 Daniel Lednicer
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 06:02
CPC Classifications
C; C07; C07D; C07D295/00; C07D295/04; C07D295/08; C07D295/096; C07C; C07C255/00; C07C309/00; C07C35/00; C07C35/21; C07C45/00; C07C45/45; C07C45/46; C07C49/00; C07C49/76; C07C49/80; C07C49/84; C07D317/00; C07D317/08; C07D317/72; C07D319/00; C07D319/04; C07D319/06
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
179 words
A compound of the formula ##SPC13## wherein Ar is an aromatic ring selected from the group consisting of phenyl and naphthyl each of which has from zero through three substituents independently selected from the group consisting of fluorine, chlorine, bromine, lower alkyl of one through three carbon atoms, lower alkoxy of one through three carbon atoms, and lower alkylthio of one through three carbon atoms; Z is selected from the group consisting of hydrogen, hydroxy and loweralkanoyloxy of one through four carbon atoms; ˜ is a generic expression denoting cis and trans stereoconfiguration and mixtures thereof, with the proviso that when the stereoconfirguration of the linkage connecting the cyclohexane ring and CH 2 Z is cis to the amino group, the linkage connecting the cyclohexane and Ar rings is always trans, and vice versa; R 1 is selected from the group consisting of hydrogen and lower alkyl of one through three carbon atoms; R 2 is ##EQU2## wherein n is 2 through 5 and Ar has the same meaning as above and a pharmacologically acceptable acid addition salt thereof.
Claim 2
Dependent Claim
179 words
A compound of the formula ##SPC13## wherein Ar is an aromatic ring selected from the group consisting of phenyl and naphthyl each of which has from zero through three substituents independently selected from the group consisting of fluorine, chlorine, bromine, lower alkyl of one through three carbon atoms, lower alkoxy of one through three carbon atoms, and lower alkylthio of one through three carbon atoms; Z is selected from the group consisting of hydrogen, hydroxy and loweralkanoyloxy of one through four carbon atoms; ˜ is a generic expression denoting cis and trans stereoconfiguration and mixtures thereof, with the proviso that when the stereoconfirguration of the linkage connecting the cyclohexane ring and CH 2 Z is cis to the amino group, the linkage connecting the cyclohexane and Ar rings is always trans, and vice versa; R 1 is selected from the group consisting of hydrogen and lower alkyl of one through three carbon atoms; R 2 is ##EQU2## wherein n is 2 through 5 and Ar has the same meaning as above and a pharmacologically acceptable acid addition salt thereof.
Claim 3
Dependent Claim
36 words
A compound of claim 1 wherein Ar is phenyl having trans stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-trans-(hydroxymethyl)-4-cis-phenyl-r-1-cyclohexyl]-amino]butyrophenone hydrochloride.
Claim 4
Dependent Claim
36 words
A compound of claim 1 wherein Ar is phenyl having cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-cis-(hydroxymethyl)-4-trans-phenyl-r-1-cyclohexyl]amino]butyrophenone hydrochloride.
Claim 5
Dependent Claim
36 words
A compound of claim 1 wherein Ar is p-fluorophenyl having trans stereoconfiguration Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-trans-(p-fluorophenyl)-4-cis-(hydroxymethyl)-r-1-cyclohexyl]amino]butyophenone hydrochloride.
Claim 6
Dependent Claim
36 words
A compound of claim 1 wherein Ar is p-fluorophenyl having cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-cis-(p-fluorophenyl)-4-trans-(hydroxymethyl)-r-1-cyclohexyl]-amino]butyrophenone hydrochloride.
Claim 7
Dependent Claim
36 words
A compound of claim 1 wherein Ar is p-methoxyphenyl having trans stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-cis-(hydroxymethyl)-4-trans-(p-methoxyphenyl)-r-1-cyclohexyl]amino]butyrophenone hydrochloride.
Claim 8
Dependent Claim
36 words
A compound of claim 1 wherein Ar is p-methoxyphenyl having cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-trans-(hydroxymethyl)-4-cis-(p-methoxyphenyl)-r-1-cyclohexyl]amino]butyrophenone hydrochloride.
Claim 9
Dependent Claim
36 words
A compound of claim 1 wherein Ar is p-chlorophenyl having trans stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4-[[4-trans-(p-chlorophenyl)-4-cis(-hydroxymethyl)-r-1-cyclohexyl]amino]-4'-fluorobutyrophenone hydrochloride.
Claim 10
Dependent Claim
36 words
A compound of claim 1 wherein Ar is p-chlorophenyl having cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4-[[4-cis-(-p-chlorophenyl)-4-trans-(hydroxymethyl)-r-1-cyclohexyl]-amino]-4'-fluorobutyrophenone hydrochloride.
Claim 11
Dependent Claim
36 words
A compound of claim 1 wherein Ar is 1-naphthyl having trans stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-cis-(hydroxymethyl)-4-trans-(1-naphthyl)-r-1-cyclohexyl]amino]-butyrophenone hydrochloride.
Claim 12
Dependent Claim
36 words
A compound of claim 1 wherein Ar is 1-naphthyl having cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-trans-(hydroxymethyl)-4-cis-(1-naphthyl)-r-1-cyclohexyl]amino]butyrophenone hydrochloride.
Claim 13
Dependent Claim
38 words
A compound of claim 1 wherein Ar is phenyl having trans stereoconfiguration, Z is acetoxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-cis-(hydroxymethyl)-4-trans-phenyl-r-1-cyclohexyl]amino]butyrophenone, acetate (ester) hydrochloride.
Claim 14
Dependent Claim
38 words
A compound of claim 1 wherein Ar is phenyl having cis stereoconfiguration, Z is acetoxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-trans-(hydroxymethyl)-4-cis-phenyl-r-1-cyclohexyl[amino]-butyrophenone, acetate (ester) hydrochloride.
Claim 15
Dependent Claim
38 words
A compound of claim 1 wherein Ar is p-methoxyphenyl having trans stereoconfiguration, Z is acetoxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-cis-(hydroxymethyl)-4-trans-(p-methoxyphenyl)-r-1-cyclohexyl]amino]butyrophenone, acetate (ester) hydrochloride.
Claim 16
Dependent Claim
38 words
A compound of claim 1 wherein Ar is p-methoxyphenyl- having cis stereoconfiguration, Z is acetoxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[[4-trans-(hydroxymethyl)-4-cis-(p-methoxyphenyl)-r-1-cyclohexyl]amino]butyrophenone, acetate (ester) hydrochloride.
Claim 17
Dependent Claim
35 words
A compound of claim 1 wherein AR is phenyl having trans stereoconfiguration, Z and R 1 are hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[(4-cis-methyl-4-trans-phenyl-r-1-cyclohexyl)amino]butyrophenone hydrochloride.
Claim 18
Dependent Claim
36 words
A compound of claim 1 wherein in Ar is phenyl having cis stereoconfiguration, Z and R 1 are hydrogen, R 2 is 4-oxo-4-(p-fluorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4'-fluoro-4-[(4-trans-methyl-4-cis-phenyl-r-1-cyclohexyl)amino]butyrophenone hydrochloride.
Claim 19
Dependent Claim
26 words
A compound of claim 18 wherein Ar is phenyl having trans stereoconfiguration, Z is hydroxy, R 1 is hydrogen and R 2 is 4-oxo-4-phenylbutyl, namely, 4-[[4-cis-(hydroxymethyl)-4-trans-phenyl-r-1-cyclohexyl]amino]butyrophenone.
Claim 20
Dependent Claim
26 words
A compound of claim 1 wherein Ar is phenyl having cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen and R 2 is 4-oxo-4-phenylbutyl, namely, 4-[[4-trans-(hydroxymethyl)-4-cis-phenyl-r-1-cyclohexyl]amino]butyrophenone.
Claim 21
Dependent Claim
26 words
A compound of claim 1 wherein Ar is phenyl having trans stereoconfiguration, Z is hydroxy, R 1 is hydrogen and R 2 is 4-oxo-4-(p-methylphenyl)butyl, namely, 4-[[4-cis-(hydroxymethyl)-4-trans-phenyl-r-1-cyclohexyl]amino]-4'-methylbutyrophenone.
Claim 22
Dependent Claim
25 words
A compound of claim 1 wherein Ar is phenyl cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen, and R 2 is 4-oxo-4-(p-methylphenyl)butyl, namely, 4-[[4-trans-(hydroxymethyl)-4-cis-phenyl-r-1-cyclohexyl]amino]-4'-methylbutyrophenone.
Claim 23
Dependent Claim
26 words
A compound of claim 1 wherein Ar is phenyl having trans stereoconfiguration, Z is hydroxy, R 1 is hydrogen and R 2 is 4-oxo-4-(p-methoxyphenyl)butyl, namely, 4-[[4-cis-(hydroxymethyl)-4-trans-phenyl-r-1-cyclohexyl]amino]-4'-methoxybutyrophenone.
Claim 24
Dependent Claim
26 words
A compound of claim 1 wherein Ar is phenyl having cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen and R 2 is 4-oxo-(p-methoxyphenyl)butyl, namely, 4-[[4-trans(hydroxymethyl)-4-cis-phenyl-r1-cyclohexyl]amino]-4'-methoxybutyrophenone.
Claim 25
Dependent Claim
36 words
A compound of claim 1 wherein Ar is phenyl having trans stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-chlorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4-[[4-cis-(hydroxymethyl)-4-trans-phenyl-r-1-cyclohexyl]amino]-4'-chlorobutyrophenone hydrochloride.
Claim 26
Dependent Claim
36 words
A compound of claim 1 wherein Ar is phenyl having cis stereoconfiguration, Z is hydroxy, R 1 is hydrogen, R 2 is 4-oxo-4-(p-chlorophenyl)butyl and the acid addition salt is that of hydrochloric acid, namely, 4-[[4-trans-(hydroxymethyl)-4-cis-phenyl-r-1-cyclohexyl]amino]-4'-chlorobutyrophenone hydrochloride.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1979-09-07 | 1980-03-08 | 1980-09-07 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1983-09-07 | 1984-03-08 | 1984-09-07 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1987-09-07 | 1988-03-08 | 1988-09-07 | $7700.00 | Window Closed / Lapsed |