Back to results
US 2011/0218186 A1Published application
Spirocyclic heterocyclic derivatives and methods of their use
AssigneeAdolor Corporation
InventorsRoland E. Dolle, Bertrand Le Bourdonnec, Guo-Hua Chu
Life of this patent
Estimating the term…
Abstract
Spirocyclic heterocyclic derivatives, pharmaceutical compositions containing these compounds, and methods for their pharmaceutical use are disclosed. In certain embodiments, the spirocyclic heterocyclic derivatives are ligands of the δ opioid receptor and may be useful, inter alia, for treating and/or preventing pain, anxiety, gastrointestinal disorders, and other δ opioid receptor-mediated conditions.
Claims56
A pharmaceutical composition, comprising:
- a pharmaceutically acceptable carrier;
- and a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
8 more elements
A method of binding opioid receptors in a patient in need thereof, comprising the step of:
- administering to said patient an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating a condition, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof;
- said condition selected from any one of the group consisting of:
- pain, gastrointestinal dysfunction, a urogenital disorder, an immunomodulatory disorder, an inflammatory disorder, a mood disorder, anxiety, a respiratory function disorder, a stress-related disorder, attention deficit hyperactivity disorder, a sympathetic nervous system disorder, tussis, a motor disorder, stroke, cardiac arrhythmia, glaucoma, sexual dysfunction, and substance addiction.
9 more elements
A method of preventing, inhibiting or treating a condition, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof;
- said condition selected from any one of the group consisting of:
- shock, brain edema, cerebral ischemia, cerebral deficits subsequent to cardiac bypass surgery and grafting, systemic lupus erythematosus, Hodgkin's disease, Sjogren's disease, epilepsy, and rejection in organ transplants and skin grafts.
9 more elements
A method of improving organ and cell survival, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating pain, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating a urogenital disorder, comprising the step of:
- administering to a patient in need thereof an effective amount a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating an inflammatory disorder, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating a mood disorder, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating anxiety, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating a motor dysfunction, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating cardiac arrhythmia, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
A method of preventing, inhibiting or treating sexual dysfunction, comprising the step of:
- administering to a patient in need thereof an effective amount of a compound according to formula XXVIII:
- wherein:
- D is:
- K is carboxy (—COOH), —C(═O)—O-alkyl, —S(═O)2—N(alkyl)(alkyl), heteroaryl, alkylheteroaryl, aminocarbonyl (—C(═O)—NH2), or N-alkylaminocarbonyl (—C(═O)—NH(alkyl));
- R23, R24, and R26 are each independently H or alkyl;
- p is 1;
- A2 and B2 are each H, or together form a double bond;
- and
- X2 is —CH2— or —O—;
- or a stereoisomer, prodrug, pharmaceutically acceptable salt, hydrate, solvate, acid salt hydrate, or N-oxide thereof.
7 more elements
Dependencies are inferred from the claim text.