Tricyclic dihydropyrazolone and tricyclic dihydroisoxazolone potassium channel openers
AssigneeAbbott Laboratories
InventorsIrene Drizin, Robert J. Altenbach, William A. Carroll
Life of this patent
Estimating the term…
Abstract
Compounds of formula I 1 are useful in treating diseases prevented by or ameliorated with potassium channel openers. Also disclosed are potassium channel opening compositions and a method of opening potassium channels in a mammal.
Claims51
A compound having formula I:
- 35
- or a pharmaceutically acceptable salt thereof wherein,
- m is an integer 1-2;
- n is an integer 0-1;
- provided that when m is 2, n is 0;
- R1 is selected from the group consisting of aryl and heterocycle;
- Q is selected from the group consisting of C(O), S(O), and S(O)2;
- V is selected from the group consisting of C(R2)(R3), O, S, and NR4;
- R2 and R3 are independently absent or selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkyl, alkylthio, alkynyl, aryl, arylalkoxy, arylalkenyl, arylalkyl, carboxy, cyano, cycloalkyl, cycloalkylalkyl, haloalkoxy, haloalkyl, halogen, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, oxo, NR5R6, and (NR5R6)alkyl;
- R4 is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkyl, alkynyl, aryl, arylalkoxy, arylalkenyl, arylalkyl, cyano, cycloalkyl, cycloalkylalkyl, haloalkoxy, haloalkyl, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, —NR5R6, and (NR5R6)alkyl;
- R5 and R6 are independently selected from the group consisting of hydrogen and lower alkyl;
- X is selected from the group consisting of O and N;
- A is absent or selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, alkynyl, aryl, arylalkoxy, arylalkenyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkoxy, haloalkyl, halogen, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, —NR5R6, and (NR5R6)alkyl;
- B is selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkoxycarbonyl, alkyl, alkylcarbonyl, alkynyl, aryl, arylalkoxy, arylalkenyl, arylalkyl, cycloalkyl, cycloalkylalkyl, haloalkoxy, haloalkyl, haloalkylcarbonyl, halogen, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, —NR5R6, and (NR5R6)alkyl;
- or X is N and A and B together with the nitrogen atoms to which they are attached form a 5 or 6 membered ring;
- and
- D and E are independently selected from the group consisting of hydrogen, alkenyl, alkoxy, alkoxyalkoxy, alkoxyalkyl, alkyl, alkylthio, alkynyl, aryl, arylalkoxy, arylalkenyl, arylalkyl, carboxy, cyano, cycloalkyl, cycloalkylalkyl, haloalkoxy, haloalkyl, halogen, heterocycle, heterocyclealkyl, hydroxy, hydroxyalkyl, oxo, —NR5R6, and (NR5R6)alkyl;
- provided that when Q is S(O) or S(O)2 and n is 0, then V is C(R2)(R3).
The method of claim 48 wherein the disorder is selected from the group consisting of asthma, epilepsy, Raynaud's syndrome, intermittent claudication, migraine, pain, pollakiuria, bladder instability, nocturia, bladder hyperreflexia, enuresis, alopecia, cardioprotection, ischemia, eating disorders, functional bowel disorders, and neurodegeneration.
The method of claim 48 wherein the disorder is bladder overactivity.
The method of claim 48 wherein the disorder is benign prostatic hyperplasia.
The method of claim 48 wherein the disorder is dysmenorrhea.
The method of claim 48 wherein the disorder is premature labor.
The method of claim 48 wherein the disorder is urinary incontinence.
The method of claim 48 wherein the disorder is selected from the group consisting of male erectile dysfunction and premature ejaculation.
The method of claim 48 wherein the disorder is female sexual dysfunction.
Dependencies are inferred from the claim text.