Pharmaceutical compounds

Abstract

Tricyclic pyrazole derivatives of the following formula (I) having affinity for the cannabinoidergic CB1 and/or CB2 receptors: wherein: A represents a group selected from one of the following: (CH 2 ) t —, —(CH 2 )—S(O) z —, or —S(O) z —(CH 2 )—, B is a heteroaryl, optionally substituted; R is a group selected from the following: alkyl, aryl, arylalkyl or arylalkenyl, not substituted or having from one to four substituents, equal to or different from each other; R′ is a group selected from the following: an ether group of formula —(CH 2 )—O—(CH 2 ) v —R″, a ketonic group of formula —C(O)—Z′, wherein Z′ is as defined below; a substituent having an hydroxyl function of formula —CH(OH)—Z′; an amide substituent of formula —C(O)—NH-T′.

1 - 18 . (canceled) 
     
     
         19 . A method of treating or preventing a disease or condition involving the CB1 or CB2 receptors of a mammal comprising administering to the mammal a compound having the following chemical structure: 
       
         
           
           
               
               
           
         
         wherein:
 A represents
 (CH 2 ) t− , wherein: 
 t is equal to 1, 2 or 3; 
 z is equal to 0, 1 or 2; 
 
 B is a heteroaryl with a ring having 5 or 6 atoms selected from the following: thiophene, furan, oxazole, thiazole, imidazole, isoxazole, isothiazole, triazole, pyridazine, pyrazine, triazine, or pyrrole, optionally substituted with a number of substituents from 1 to 4, said substituents being equal to or different from each other and selected from the following: halogen, C 1 -C 7  alkyl, C 1 -C 7  alkylthio, C 1 -C 7  alkoxy, C 1 -C 7  haloalkyl, C 1 -C 7  haloalkoxy, cyano, nitro, amino, N-alkylamino, N,N-dialkylamino, isothiocyanate, phenyl, cycloalkyl, saturated or unsaturated heterocycle, heteroaryl; 
 R is
 linear or branched C 1 -C 10  alkyl, wherein the end of the main chain not linked to the nitrogen atom has —CH 2 —W termination, W being a group selected from hydrogen, halogen, isothiocyanate, CN, OH, OCH 3 , NH 2 , —CH═CH 2 ; 
 or aryl, arylalkyl or arylalkenyl, not substituted or having from one to five substituents, equal to or different from each other, selected from halogen, C 1 -C 7  alkyl, C 1 -C 7  alkylthio, C 1 -C 7  alkoxy, C 1 -C 7  haloalkyl, C 1 -C 7  haloalkoxy, cyano, nitro, amino, N-alkylamino, N,N-dialkylamino, saturated or unsaturated heterocycle, or phenyl; 
 
 R′ is
 a ketonic group of formula —C(O)—Z′, wherein Z′ is a C 1 -C 8  alkyl or a C 3 -C 15  cycloalkyl, a saturated or unsaturated heterocycle, or an aryl, or a heteroaryl; 
 or an amidic substituent of formula —C(O)—NH-T′, T′ being selected from:
 C 1 -C 8  alkyl; 
 C 1 -C 7  haloalkyl; 
 aryl, arylalkyl or arylalkenyl, optionally containing one heteroatom selected from S, N, O, not substituted or optionally having from one to four substituents, equal to or different from each other, said substituents selected from halogen, C 1 -C 7  alkyl, C 1 -C 7  haloalkyl, C 1 -C 7  haloalkoxy, C 1 -C 7  alkylthio, or C 1 -C 7  alkoxy; 
 a C 3 -C 15  cycloalkyl not substituted or substituted with one or more C 1 -C 7  alkyl chains, said chains being from one to four chains for C 5 -C 15  cycloalkyls, one to three chains for the C 4  cycloalkyl, being from one to two for the C 3  cycloalkyl, said alkyl groups being equal to or different from each other; 
 
 a group of formula (IA): 
 
 
       
       
         
           
           
               
               
           
         
       
       wherein R 3  and R 4  equal to or different from each other represent hydrogen or C 1 -C 3  alkyl, with the proviso that R 3  and R 4  are not both hydrogen;
     a group of formula (IB):     
 
       
         
           
           
               
               
           
         
       
       wherein R 5  represents a C 1 -C 3  alkyl and k is an integer between 1 and 3;
     or a group NR 1 R 2 , wherein R 1  and R 2 , equal or different and are
 hydrogen; 
 C 1 -C 7  alkyl; 
 aryl, arylalkyl or arylalkenyl not substituted or optionally having on the aromatic rings from one to five substituents, equal to or different from each other, selected from halogen, C 1 -C 7  alkyl, C 1 -C 7  haloalkyl, C 1 -C 7  haloalkoxy, C 1 -C 7  alkylthio, C 1 -C 7  alkoxy; 
     
 or R 1  and R 2  together with the nitrogen atom to which they are linked form a saturated or unsaturated, heterocycle from 5 to 10 carbon atoms, not substituted or optionally having from one to four substituents, equal to or different from each other, selected from the group consisting of: C 1 -C 7  alkyl, phenyl, and benzyl, said phenyl or benzyl optionally substituted with one or more groups, equal to or different from each other, selected from: halogen, C 1 -C 7  alkyl, C 1 -C 7  haloalkyl, C 1 -C 7  haloalkoxy, C 1 -C 7  alkylthio, C 1 -C 7  alkoxy or pharmaceutically acceptable salts or reactive derivatives, wherein the selective derivatives are selected from the group consisting of acyl halides, anhydrides, mixed anhydrides, imidazolides, ester-amide adducts, or linear or branched C 1 -C 4  alkyl esters thereof. 
 
     
     
         20 . The method of  claim 19 , wherein the compound has affinity for the CB2 receptors of the mammal. 
     
     
         21 . The method of  claim 19 , wherein the disease or condition involves immune system cells or immune disorders. 
     
     
         22 . The method of  claim 19 , wherein the disease or condition is selected from the group consisting of: osteoporosis, renal ischemia, inflammation, organ transplant rejection, allogenic transplant rejection, GVHD (Graft Versus Host Disease), erythematosus systemic lupus, ankylosing spondylitis, rheumatoid polyarthritis, autoimmune hemolytic anemia, Behcet disease, Sjogren syndrome, undifferentiated spondylarthritis, reactive arthritis, dermatomyositis. 
     
     
         23 . The method of  claim 19 , wherein the compound has affinity for the CB1 receptors of the mammal. 
     
     
         24 . The method of  claim 19 , wherein the disease or condition is selected from the group consisting of ocular diseases, lung diseases, allergies and allergic reactions. 
     
     
         25 . The method of  claim 19 , wherein the disease or condition is selected from the group consisting of schizophrenia, depression, substance abuse, pain, vomit, nausea, vertigo, neuropathy, hemicranias, stress, psychosomatic diseases and conditions, epilepsy, Tourette syndrome, Parkinson's disease, Huntington's disease, Alzheimer's disease, senile dementia, cognitive disease and memory loss, anoxia, low-appetite, gastrointestinal tract disease, bladder disease, cardiovascular disease, urinary system disease, and neuroinflammatory disease. 
     
     
         26 . The method of  claim 19 , wherein A=(CH 2 ) t  and wherein t=2 or 3. 
     
     
         27 . The method of  claim 19 , wherein A=(CH 2 ) t  and wherein t=1. 
     
     
         28 - 29 . (canceled)