Substituted piperidine spiro pyrrolidinone and piperidinone, preparation and therapeutic use thereof
AssigneeSanofi
InventorsZhongli GAO, Daniel HALL, Ryan HARTUNG
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Abstract
The present disclosure relates to a series of substituted N-phenyl-bipyrrolidine carboxamides of formula (I). wherein R1, R2, R3, m, n and p are as described herein. More specifically, the compounds of this invention are modulators of H3 receptors and are, therefore, useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of diseases modulated by H3 receptors including diseases associated with the central nervous system. Additionally, methods of preparation of substituted N-phenyl-bipyrrolidine carboxamides and intermediates therefor are disclosed.
Claims16
A method of treating a disease in a patient, said disease selected from the group consisting of a sleep disorder, dementia, Alzheimer's disease, multiple sclerosis, cognitive disorder, attention deficit hyperactivity disorder and depression, comprising administering to said patient a therapeutically effective amount of a compound of formula (I):
- wherein
- m is 1 or 2;
- n is 1 or 2;
- p is 1 or 2;
- R1 is hydrogen, (C1-C4)alkyl, CF3, or (C1-C4)alkoxy-(C1-C4)alkyl;
- R2 is hydrogen, halogen, (C1-C4)alkyl or CF3;
- and
- R3 is hydrogen, (C1-C4)alkyl, (C1-C6)alkyloxycarbonyl, (C3-C7)cycloalkyl(C1-C6)alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted heterocycloalkyl(C1-C6)alkyl, substituted or unsubstituted 5- or 6-membered ring heteroaryl(C1-C6)alkyl, substituted or unsubstituted benzyl, (C1-C4)alkoxymethylcarbonyl, substituted or unsubstituted (C3-C7)cycloalkanecarbonyl, substituted or unsubstituted benzylcarbonyl, substituted or unsubstituted (C6-C10)arylcarbonyl, substituted or unsubstituted 5 or 6-membered ring heteroarylcarbonyl, substituted or unsubstituted heterocyclecarbonyl, substituted or unsubstituted benzenesulfonyl, wherein the substituents are selected from halogen, trifluoromethoxy, (C1-C4)alkoxy, (C1-C4)alkyl and CF3;
- or a salt, enantiomer or diastereomer thereof.
A method for treating a disease in a patient, said disease selected from the group consisting of cognitive impairment associated with schizophrenia (CIAS), an anxiety disorder, panic disorder and post-traumatic stress disorder, major depressive disorder, dementia of Alzheimer type (DAT), cognitive deficits related to neurological diseases chosen from Alzheimer, Parkinson or Huntington, age related cognitive impairment, mild cognitive impairment, vascular dementia, Lewis Body dementia, cognition associated with cognitive deficits, and obesity, comprising administering to said patient a therapeutically effective amount of a compound of formula (I):
- wherein
- m is 1 or 2;
- n is 1 or 2;
- p is 1 or 2;
- R1 is hydrogen, (C1-C4)alkyl, CF3, or (C1-C4)alkoxy-(C1-C4)alkyl;
- R2 is hydrogen, halogen, (C1-C4)alkyl or CF3;
- and
- R3 is hydrogen, (C1-C4)alkyl, (C1-C6)alkyloxycarbonyl, (C3-C7)cycloalkyl(C1-C6)alkyl, substituted or unsubstituted heterocycle, substituted or unsubstituted heterocycloalkyl(C1-C6)alkyl, substituted or unsubstituted 5- or 6-membered ring heteroaryl(C1-C6)alkyl, substituted or unsubstituted benzyl, (C1-C4)alkoxymethylcarbonyl, substituted or unsubstituted (C3-C7)cycloalkanecarbonyl, substituted or unsubstituted benzylcarbonyl, substituted or unsubstituted (C6-C10)arylcarbonyl, substituted or unsubstituted 5 or 6-membered ring heteroarylcarbonyl, substituted or unsubstituted heterocyclecarbonyl, substituted or unsubstituted benzenesulfonyl, wherein the substituents are selected from halogen, trifluoromethoxy, (C1-C4)alkoxy, (C1-C4)alkyl and CF3;
- or a salt, enantiomer or diastereomer thereof.
Dependencies are inferred from the claim text.