Substituted 5-vinylphenyl-1-phenyl-pyrazole cannabinoid modulators

Abstract

This invention is directed to a cannabinoid modulator compound of formula (I): or a form thereof, and methods for use in treating, ameliorating or preventing a cannabinoid receptor mediated syndrome, disorder or disease.

1 .- 23 . (canceled) 
     
     
         24 . A method for treating, ameliorating or preventing a cannabinoid receptor mediated syndrome, disorder or disease in a subject in need thereof comprising the step of administering to the subject an effective amount of the compound of Formula 1 
       
         
           
           
               
               
           
         
       
       or a form thereof, wherein
 R 1a  is hydrogen or alkyl; 
 R 1b  is selected from C 3-12 cycloalkyl, heterocyclyl, aryl, heteroaryl or alkyl, wherein alkyl is optionally substituted with carboxy, C 3-12 cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein each instance of C 3-12 cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally substituted with one, two, three or four substituents selected from alkyl, alkoxy, cyano, halogen, hydroxy, amino or alkylamino, and 
 wherein heterocyclyl optionally has one nitrogen ring atom attached to the formula (I) nitrogen atom, wherein said nitrogen ring atom is optionally further substituted with alkyl to form a quaternary ammonium salt; alternatively, R 1a  and R 1b  are taken to ether with the nitro en atom of attachment to form a ring selected from piperidinyl or piperazinyl; and, 
 R 2  and R 3  are each selected from one or two alkyl, alkoxy, cyano or halogen substituents. 
 
     
     
         25 . The method of  claim 24 , wherein the syndrome, disorder or disease is related to appetite, metabolism, diabetes, glaucoma-associated intraocular pressure, social and mood disorders, seizures, substance abuse, learning, cognition or memory, organ contraction or muscle spasm, bowel disorders, respiratory disorders, locomotor activity or movement disorders, immune and inflammation disorders, unregulated cell growth, pain management or neuroprotection. 
     
     
         26 . The method of  claim 24 , wherein the effective amount of the compound is from about 0.001 mg/kg/day to about 300 mg/kg/day. 
     
     
         27 . The method of  claim 24 , further comprising treating, ameliorating or preventing a CB1 receptor inverse-agonist mediated appetite related, obesity related or metabolism related syndrome, disorder or disease in a subject in need thereof comprising the step of administering to the subject an effective amount of the compound, wherein the compound is an inverse-agonist of the receptor. 
     
     
         28 . The method of  claim 24 , wherein the effective amount of the compound is from about 0.001 mg/kg/day to about 300 mg/kg/day. 
     
     
         29 . The method of  claim 24 , further comprising the step of administering to the subject a combination product comprising an effective amount of the compound and a therapeutic agent, wherein the therapeutic agent is an anticonvulsant or a contraceptive agent. 
     
     
         30 . The method of  claim 29 , wherein the anticonvulsant is topiramate, analogs of topiramate, carbamazepine, valproic acid, lamotrigine, gabapentin, phenytoin and the like and mixtures or pharmaceutically acceptable salts thereof. 
     
     
         31 . The method of  claim 29 , wherein the contraceptive agent is a progestin-only contraceptive, a contraceptive having a progestin component and an estrogen component, or an oral contraceptive optionally having a folic acid component. 
     
     
         32 . The method of contraception in a subject comprising the step of administering to the subject a composition, wherein the composition comprises a contraceptive and the compound of  claim 24 , wherein the composition reduces the urge to smoke in the subject or assists the subject in losing weight or both, and wherein the compound of  claim 24  is a CB1 receptor inverse-agonist or antagonist. 
     
     
         33 - 34 . (canceled)