Back to results
US 2006/0079559 A1Published application
S-isomer of 2-{2[N-(2-indanyl)-N-phenylamino]ethyl}piperidine and other dermal anesthetics
AssigneeBridge Pharma, Inc.
InventorsGunnar Aberg, Jan Chen
Life of this patent
Estimating the term…
Abstract
The present invention relates to the S-isomers of anesthetic compounds, the methods of treatment therewith, the compounds being useful for inducing local anesthesia, analgesia and sleep.
Claims76
A substantially pure S-isomer of a compound having the formula:
- or a pharmaceutically acceptable salt, base, or mixture thereof, wherein n is equal to 0, 1, 2, or 3, Z represents two hydrogen atoms or an oxygen atom, the (CH2)n group having a straight or branched chain, B represents hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
- in which R3 and R4 may independently be selected from the group consisting of methoxy, ethoxy, a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms, whereby R3 may also represent hydrogen, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent in the ortho, meta and/or para position, and R1 represents a hydrogen, or a lower alkyl or hydroxyalkyl containing 1 to 4 carbon atoms and the piperidine nucleus is attached at the 2-, 3-, or 4-position, wherein the compound is useful for inducing anesthesia and analgesia in a patient in need thereof.
A pharmaceutical formulation for providing anesthesia and analgesia in a patient in need thereof, comprising:
- a therapeutically effective amount of substantially pure S-isomer of a compound of formula:
- or pharmaceutically acceptable salt, base, or mixture thereof, wherein n is equal to 0, 1, 2, or 3, Z represents two hydrogen atoms or an oxygen atom, the (CH2)n group having a straight or branched chain, B represents hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
- in which R3 and R4 may independently be selected from the group consisting of methoxy, ethoxy, a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms, whereby R3 may also represent hydrogen, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent in the ortho, meta and/or para position, and R1 represents a hydrogen, or a lower alkyl or hydroxyalkyl containing 1 to 4 carbon atoms and the piperidine nucleus is attached at the 2-, 3-, or 4-position, and a pharmaceutically acceptable excipient.
A method of inducing anesthesia in a patient in need thereof, comprising:
- administering to a discrete site in a patient in need thereof an anesthetic inducing amount of a substantially pure S-isomer of a compound of formula:
- or pharmaceutically acceptable salt, base, or mixture thereof, wherein n is equal to 0, 1, 2, or 3, Z represents two hydrogen atoms or an oxygen atom, the (CH2)n group having a straight or branched chain, B represents hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
- in which R3 and R4 may independently be selected from the group consisting of methoxy, ethoxy, a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms, whereby R3 may also represent hydrogen, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent in the ortho, meta and/or para position, and R1 represents a hydrogen, or a lower alkyl or hydroxyalkyl containing 1 to 4 carbon atoms and the piperidine nucleus is attached at the 2-, 3-, or 4-position,
- wherein administration of the compound to the discrete site provides a duration of action that is longer than that of lidocaine administration to the discrete site.
1 more element
A method of providing analgesia or alleviating pain in a patient in need thereof, comprising:
- administering to a discrete site in a patient in need thereof an anesthetic inducing amount of a substantially pure S-isomer of a compound of formula:
- or pharmaceutically acceptable salt, base, or mixture thereof, wherein n is equal to 0, 1, 2, or 3, Z represents two hydrogen atoms or an oxygen atom, the (CH2)n group having a straight or branched chain, B represents hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
- in which R3 and R4 may independently be selected from the group consisting of methoxy, ethoxy, a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms, whereby R3 may also represent hydrogen, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent in the ortho, meta and/or para position, and R1 represents a hydrogen, or a lower alkyl or hydroxyalkyl containing 1 to 4 carbon atoms and the piperidine nucleus is attached at the 2-, 3-, or 4-position,
- wherein administration of the compound to the discrete site provides a duration of action that is longer than that of lidocaine administration to the discrete site.
1 more element
A method of improving sleep in a patient in need thereof, comprising:
- administering to a discrete site in a patient in need thereof an anesthetic inducing amount of a substantially pure S-isomer of a compound of formula:
- or pharmaceutically acceptable salt, base, or mixture thereof, wherein n is equal to 0, 1, 2, or 3, Z represents two hydrogen atoms or an oxygen atom, the (CH2)n group having a straight or branched chain, B represents hydrogen, an alkoxy radical containing 1 to 3 carbon atoms or a group of the formula
- in which R3 and R4 may independently be selected from the group consisting of methoxy, ethoxy, a lower alkyl or hydroxyalkyl radical containing 1 to 3 carbon atoms, whereby R3 may also represent hydrogen, A is a 2-pyridyl radical, an unsubstituted phenyl radical or a phenyl radical substituted by at least one substituent in the ortho, meta and/or para position, and R1 represents a hydrogen, or a lower alkyl or hydroxyalkyl containing 1 to 4 carbon atoms and the piperidine nucleus is attached at the 2-, 3-, or 4-position,
- wherein administration of the compound to the discrete site provides a duration of action longer than that of lidocaine administration to the discrete site,
- wherein administration of the compound alleviates pain experienced by the patient and provides for improved sleep resulting from the alleviation of pain.
2 more elements
A process for preparing S-2-{2-[N-(2-indanyl)-N-phenylamino]ethyl}piperidine (S-LAC-34) comprising:
- a) sequentially converting:
- i) an N-protected L-pipecolic acid to a corresponding diazomethyl ketone;
- ii) the diazomethyl ketone to a methyl ester;
- iii) the methyl ester to a primary alcohol;
- and
- iv) the primary alcohol to an S-alkyl halide;
- b) reacting the S-alkyl halide with 2-(phenylamino)indane;
- and
- c) removing an N-protecting group to obtain S-2-{2-[N-(2-indanyl)-N-phenylamino]ethyl}piperidine (S-LAC-34).
6 more elements
A method of preparing an S-isomer of a compound of formula 1:
- comprising:
- a) by reacting a compound of formula 2
- with an S-enantiomer of a compound of formula 3,
- wherein R1 represents a lower alkyl or hydroxyalkyl containing 1 to 4 carbon atoms or a substituted or unsubstituted phenyl and X is a halogen (bromo, chloro, fluoro, iodo) or a reactive esterified hydroxyl group, to form a compound of formula 1;
- and
- b) hydrogenating a compound of formula 1 , wherein R1 is a residue removable by means of hydrogenolysis to give a compound of formula 1, wherein R1 is hydrogen;
- and
- c) hydrolyzing a compound of formula 1, wherein R1 is a residue removable by means of hydrolysis, to form a compound of formula 1, wherein R1 is hydrogen;
- and
- d) transforming free bases obtained into their salts or transforming salts into their free bases.
7 more elements
Dependencies are inferred from the claim text.