Novel carbamates, their preparation, and pharmaceutical formulations containing these compounds

• US 4,335,138 A
• Filed: 09/15/1980
• Issued: 06/15/1982
• Est. Priority Date: 09/29/1979
• Status: Expired due to Term

• Current Assignee: BASF AG (BASF SE)
• Original Assignee: BASF AG (BASF SE)
• Inventors: Weifenbach, Harald, Lenke, Dieter, Geiss, Karl-Heinz, Kretzschmar, Rolf, Wiersdorff, Walter-Wielant, Worstmann, Wolfgang
• Primary Examiner(s): Shippen, Michael L.
• Application Number:
  US06/186,841
• Time in Patent Office: 638 Days
• Field of Search: 260/340.6, 260/340.7, 260/340.9 R, 260/345.8 R, 260/347.4, 260/464, 560/27, 560/29, 560/31, 560/32, 560/115, 560/148, 560/160, 560/161, 560/162, 549/13, 549/14, 549/21, 549/22, 549/28, 549/30, 549/38, 549/39, 549/69, 549/65, 549/20, 549/76, 549/77, 549/63, 424/275, 424/276, 424/277, 424/278, 424/283, 424/285, 424/300, 424/299
• US Class Current: 514/432
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: C07C 45/62 by hydrogenation of carbon-to-carbon double or triple bonds
• CPC Class Codes: C07C 45/69 by addition to carbon-to-carbon double or triple bonds
• CPC Class Codes: C07C 45/75 Reactions with formaldehyde
• CPC Class Codes: C07C 45/79 by solid-liquid treatment; by chemisorption
• CPC Class Codes: C07C 45/81 by change in the physical state, e.g. crystallisation
• CPC Class Codes: C07C 49/21 containing rings other than six-membered aromatic rings
• CPC Class Codes: C07C 49/337 containing hydroxy groups
• CPC Class Codes: C07C 49/345 polycyclic
• CPC Class Codes: C07C 49/543 to a six-membered ring
• CPC Class Codes: C07C 49/573 containing hydroxy groups
• CPC Class Codes: C07C 49/753 containing ether groups, groups, groups, or groups
• CPC Class Codes: C07D 307/14 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 307/52 Radicals substituted by nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 309/04 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 309/14 Nitrogen atoms not forming part of a nitro radical
• CPC Class Codes: C07D 317/28 Radicals substituted by nitrogen atoms nitro radicals C07D317/16
• CPC Class Codes: C07D 319/06 not condensed with other rings
• CPC Class Codes: C07D 333/20 by nitrogen atoms nitro, nitroso radicals C07D333/12

Abstract

Novel carbamates derived from substituted cyclic β-keto-alcohols, their preparation, and pharmaceutical formulations which contain these compounds and which may be used as hypnotics in the treatment of sleep disturbance and as sedatives.

Claims

1. A compound of the formula I ##STR44## where the broken line is a double bond which may or may not be hydrogenated and the radicals A are each hydrogen, or the two radicals A together are a bridge, joining the two carbon atoms, of the formula --(CH₂)_m --, where m is an integer from 1 to 3, and which may or may not be substituted by 1, 2 or 3 lower alkyl, or a bridge of the formula ##STR45## where n is an integer from 2 to 4, and R¹ is hydrogen, or is a saturated straight-chain or branched alkyl radical of 1 to 12 carbon atoms, which is unsubstituted, or is monosubstituted, disubstituted or trisubstituted by halogen, lower alkoxy or lower alkylthio, or is monosubstituted by cyano or by cycloalkyl of 3 to 6 carbon atoms in the ring, which ring is unsubstituted or substituted by 1, 2 or 3 lower alkyl and may, in the case of a 5-membered or 6-membered ring, have 1 or 2 carbon atoms replaced by oxygen or sulfur, or by bicycloalkyl of 5 to 8 carbon atoms in the bicyclic system, which is unsubstituted or substituted by 1, 2 or 3 lower alkyl, or is monosubstituted or disubstituted by phenyl, furyl or thienyl, which are unsubstituted or substituted by halogen, lower alkyl or lower alkoxy, or is alkenyl or alkynyl of 2 to 12 carbon atoms, alkenyl being unsubstituted or substituted by 1, 2 or 3 chlorine atoms, or is cycloalkyl of 3 to 7 carbon atoms in the ring, which ring is unsubstituted or substituted by 1, 2, 3 or 4 lower alkyl or by phenyl and may, in the case of a 5-membered or 6-membered ring, have 1 or 2 carbon atoms replaced by oxygen or sulfur, or is bicycloalkyl of 5 to 8 carbon atoms in the bicyclic system, which is saturated or unsaturated and is unsubstituted or substituted by 1, 2 or 3 lower alkyl, or is phenyl, furyl or thienyl, which is unsubstituted or monosubstituted or disubstituted by halogen, lower alkyl or lower alkoxy, R² is saturated straight-chain or branched alkyl of 1 to 6 carbon atoms and R³ and R⁴ independently of one another are each hydrogen or lower alkyl.

2. A compound of the formula I as claimed in claim 1, where the broken line is a double bond, which may or may not be hydrogenated, the radicals A are hydrogen or together form a bridge of the formula --(CH₂)_m --, where m is 1 or 2, and R¹ is saturated straight-chain or branched alkyl of 1 to 6 carbon atoms, which is unsubstituted, or is monosubstituted, disubstituted or trisubstituted by halogen, or is monosubstituted by lower alkoxy, by cyano, by lower alkylthio, by cycloalkyl of 3 to 6 carbon atoms in the ring, which is unsubstituted or substituted by lower alkyl and, in the case of a 5-membered or 6-membered ring, may contain an oxygen or a sulfur in place of 1 carbon atom or of 2 non-adjacent carbon atoms, or by furyl, or is alkenyl or alkynyl of 2 to 6 carbon atoms, alkenyl being unsubstituted or substituted by 1, 2 or 3 chlorine atoms, or is cycloalkyl of 3 to 6 carbon atoms in the ring, which is unsubstituted or substituted by 1, 2 or 3 lower alkyl, R² is methyl or ethyl and R³ and R⁴ are each hydrogen or methyl.

3. A compound of the formula I as claimed in claim 1, where the broken line is a double bond, which may or may not be hydrogenated, and the radicals A are each hydrogen or together are methylene, and R¹ is saturated, straight-chain or branched unsubstituted alkyl of 1 to 6 carbon atoms, or alkyl of 1 to 3 carbon atoms which is substituted by chlorine, by lower alkoxy of 1 to 3 carbon atoms, or by cycloalkyl of 3 or 4 carbon atoms, or is alkenyl or alkynyl of 2 to 6 carbon atoms or is cycloalkyl of 3 to 5 carbon atoms in the ring, R² is methyl and R³ and R⁴ are each hydrogen.

13. A hypnotic or sedative composition containing a hypnotic or sedative effective amount of a compound of the formula I as claimed in claim 1, as the active compound, together with conventional carriers and diluents.

14. A method of treating sleep disturbance comprising administering to a host in need thereof a hypnotic effective amount of a compound of the formula (I), as claimed in claim 1.

15. A method of treating sleep disturbance comprising administering to a host in need thereof a sedative effective amount of a compound of the formula (I), as claimed in claim 1.

4. Exo-2-(N-Isopropylcarbamyloxymethyl)-norborn-5-en-2-yl methyl ketone.

5. Exo-2-(N-n-Propylcarbamyloxymethyl)-norborn-5-en-2-yl methyl ketone.

6. Exo-2-(N-Cyclopentylcarbamyloxymethyl)-norborn-5-en-2-yl methyl ketone.

7. Exo-2-(N-Isopropylcarbamyloxymethyl)-norborn-2-yl methyl ketone.

8. Exo-2-(N-Cyclopropylcarbamyloxymethyl)-norborn-5-en-2-yl methyl ketone.

9. Exo-2-[N-(2-Methylprop-1-yl)-carbamyloxymethyl]-norborn-5-en-2-yl methyl ketone.

10. Exo-2-(N-But-2-ylcarbamyloxymethyl)-norborn-5-en-2-yl methyl ketone.

11. 1-(N-Propylcarbamyloxymethyl)-cyclohex-3-enyl methyl ketone.

12. Exo-2-[N-(1-Cyclopropylethyl)-carbamyloxymethyl]-norborn-5-en-2-yl methyl ketone.