Novel inhibitor compounds of phosphodiesterase type 10a

Abstract

The present invention relates to compounds of the formula I and their salts etc. which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders. wherein Y 1 and Y 2 are adjacent atoms in Het 1 , which are independently selected from the group consisting of carbon and nitrogen; k is 0, 1, 2 or 3; Het 1 is a bivalent monocyclic 5- or 6-membered heteroaromatic radical, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—R a as ring members, or a bivalent fused bicyclic 8-, 9- or 10-membered heteroaromatic radical, having 1, 2, 3 or 4 heteroatoms or heteroatom moieties selected from O, S, N and N—R a as ring members; Het 2 is inter alia monocyclic 5- or 6-membered hetaryl, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—R 1a as ring members, Cyc is inter alia optionally substituted monocyclic 5- or 6-membered hetaryl or optionally substituted fused 8-, 9- or 10-membered bicyclic hetaryl; Ar is optionally substituted phenylene or optionally substituted bivalent 6-membered hetaryl; R is attached to a carbon atom of Het 1 and inter alia—halogen, C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, C 1 -C 6 -alkoxy, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 3 -C 6 -cycloalkyl etc.

We claim: 
     
         1 . Compound of formula I 
       
         
           
           
               
               
           
         
         wherein 
         Y 1  and Y 2  are adjacent atoms in Het 1 , which are independently selected from the group consisting of carbon and nitrogen; 
         k is 0, 1, 2 or 3; 
         Het 1  is a bivalent monocyclic 5- or 6-membered heteroaromatic radical, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—R a  as ring members, or a bivalent fused bicyclic 8-, 9- or 10-membered heteroaromatic radical, having 1, 2, 3 or 4 heteroatoms or heteroatom moieties selected from O, S, N and N—R a  as ring members; 
         Het 2  is selected from the group consisting of
 i. saturated or partially unsaturated, 5- to 10-membered mono- or heterobicyclic radical, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, S═O, S(═O)2, N and N-R1a as ring members, 
 ii. monocyclic 5- or 6-membered hetaryl, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—R 1a  as ring members, 
 iii. bicyclic 8-, 9- or 10-membered hetaryl, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, N and N—R 1a  as ring members, 
 iv. phenyl, 
 where Het 2  may carry 1, 2 or 3 radicals R 1 ; 
 
         Cyc is selected from
 i. monocyclic 5- or 6-membered hetaryl having 1 or 2 nitrogen atoms and optionally a further heteroatom selected from O, S and N as ring members, which is unsubstituted or may carry 1, 2, 3 or 4 identical or different substituents R 2 , 
 ii. fused 8-, 9- or 10-membered bicyclic hetaryl having one heteroatom selected from O, S and N and optionally 1, 2 or 3 nitrogen atoms as ring members, where the fused bicyclic hetaryl is unsubstituted or may carry 1, 2, 3 or 4 identical or different substituents R 2 , 
 iii. phenyl, which carries a monocyclic hetaryl radical having 1 or 2 nitrogen atoms and optionally a further heteroatom selected from O, S and N as ring members, which in addition to monocyclic hetaryl, may carry 1, 2 or 3 identical or different substituents R 2a , and 
 iv. C 5 -C 8 -cycloalkyl or saturated or partially unsaturated, 5- to 10-membered heteromonocyclic or heterobicyclic radical, having 1, 2 or 3 heteroatoms or heteroatom moieties selected from O, S, S═O, S(═O) 2 , N and N—R 1a  as ring members, and which may carry 1, 2 or 3 identical or different substituents R 2b ; 
 
         Ar phenylene or bivalent 6-membered hetaryl having 1, 2 or 3 nitrogen atoms as ring members, where phenylene and bivalent 6-membered hetaryl are unsubstituted or carry 1, 2, 3 or 4 identical or different substituents R 3 , 
         R is attached to a carbon atom of Het 1  and selected from the group consisting of halogen, CN, NR 13 R 14 , C(O)NR 13 R 14 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, trimethylsilyl, C 1 -C 6 -alkylsulfanyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfanyl, fluorinated C 1 -C 6 -alkylsulfonyl, C 1 -C 4 -alkyl-OR 11 , C 1 -C 4 -alkyl-SR 12 , C 1 -C 4 -alkyl-NR 13 R 14 , C 1 -C 6 -alkoxy, OC 1 -C 4 -alkyl-OR 11 , OC 1 -C 4 -alkyl-SR 12 , OC 1 -C 4 -alkyl-NR 13 R 14 , C 2 -C 6 -alkenyloxy, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups; 
         R a  is selected from the group consisting of hydrogen, C(O)NR 13 R 14 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, trimethylsilyl, C 1 -C 4 -alkyl-OR 11 , C 1 -C 4 -alkyl-SR 12 , C 1 -C 4 -alkyl-NR 13 R 14 , C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups; 
         two radicals R or the radical R together with the radical R a , if attached to adjacent ring atoms, may also form linear C 3 -C 5 -alkanediyl, wherein 1 or 2 CH 2  moieties can be replaced by C═O, O, S, S(═O), S(═O) 2  or NR′, and where alkanediyl is unsubstituted or may carry 1 or 2 radicals selected from halogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -fluoroalkoxy; 
         R 1  is attached to a carbon atom of Het 2  and selected from the group consisting of halogen, CN, NR 13 R 14 , C(O)NR 13 R 14 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, trimethylsilyl, C 1 -C 6 -alkylsulfanyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfanyl, fluorinated C 1 -C 6 -alkylsulfonyl, C 1 -C 4 -alkyl-OR 11 , C 1 -C 4 -alkyl-SR 12 , C 1 -C 4 -alkyl-NR 13 R 14 , C 1 -C 6 -alkoxy, OC 1 -C 4 -alkyl-OR 11 , OC 1 -C 4 -alkyl-SR 12 , OC 1 -C 4 -alkyl-NR 13 R 14 , C 2 -C 6 -alkenyloxy, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups; 
         R 1a  is selected from the group consisting of hydrogen, C(O)NR 13 R 14 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, trimethylsilyl, C 1 -C 4 -alkyl-OR 11 , C 1 -C 4 -alkyl-SR 12 , C 1 -C 4 -alkyl-NR 13 R 14 , C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups; 
         R 2  is selected from the group consisting of halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -fluoroalkyl, C 1 -C 4 -fluoroalkoxy, C 1 -C 4 -alkoxy-C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, OH, hydroxy-C 1 -C 4 -alkyl, O—C 3 -C 6 -cycloalkyl, benzyloxy, C(O)O—(C 1 -C 4 -alkyl), O—(C 1 -C 4 -alkyl)-CO 2 H, NR 23 R 24 , C(O)NR 23 R 24 , C 1 -C 4 -alkyl-NR 23 R 24 , —NR 25 —C(O)—NR 23 R 24 , NR 25 —C(O)O—(C 1 -C 4 -alkyl), —NR 25 —SO 2 —R 22 , phenyl, CN, —SF 5 , —OSF 5 , —SO 2 R 22 , —SR 22 , trimethylsilyl and C 3 -C 6 -cycloalkyl, where the cycloalkyl moiety in the last radical is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups, or
 two radicals R 2 , which are bound to adjacent ring atoms may also form linear C 3 -C 5 -alkanediyl, wherein 1 or 2 CH 2  moieties can be replaced by C═O, O, S, S(═O), S(═O) 2  or NR′, and where alkanediyl is unsubstituted or may carry 1 or 2 radicals selected from halogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -fluoroalkoxy; 
 
         R 2a  has one of the meanings given for R 2  or one radical R 2a  may also be a 5- or 6-membered hetaryl having 1 or 2 nitrogen atoms and optionally a further heteroatom selected from O, S and N as ring members, where hetaryl is unsubstituted or may carry 1, 2 or 3 radicals selected from halogen, OH, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -haloalkoxy; 
         R 2b  is selected from the group consisting of halogen, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -fluoroalkyl, C 1 -C 4 -fluoroalkoxy, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy-C 1 -C 4 -alkoxy, C 1 -C 4 -alkoxy-C 1 -C 4 -alkyl, OH, hydroxy-C 1 -C 4 -alkyl, O—C 3 -C 6 -cycloalkyl, benzyloxy, C(O)O—(C 1 -C 4 -alkyl), O—(C 1 -C 4 -alkyl)-CO 2 H, NR 23 R 24 , C(O)NR 23 R 24 , C 1 -C 4 -alkyl-NR 23 R 24 , —NR 25 —C(O)—NR 23 R 24 , NR 25 —C(O)O—(C 1 -C 4 -alkyl), —NR 25 —SO 2 —R 22 , phenyl, CN, —SF 5 , —OSF 5 , —SO 2 R 22 , —SR 22  and trimethylsilyl, or
 two radicals R 2a , which are bound to adjacent ring atoms may also form a fused benzene ring or a fused 5- or 6-membered heteroaromatic ring, having 1 ring member selected from the group consisting of O, S, N or NR′ and optionally 1 or 2 further N-atoms as ring members, where the fused benzene or heteroaromatic ring is unsubstituted or may carry 1, 2, 3 or 4 radicals selected from halogen, OH, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -fluoroalkoxy; 
 
         R 3  independently of each other, are selected from the group consisting of halogen, CN, NR 33 R 34 , C(O)NR 33 R 34 , C 1 -C 6 -alkyl, C 2 -C 6 -alkenyl, C 2 -C 6 -alkynyl, trimethylsilyl, C 1 -C 6 -alkylsulfanyl, C 1 -C 6 -alkylsulfonyl, fluorinated C 1 -C 6 -alkylsulfanyl, fluorinated C 1 -C 6 -alkylsulfonyl, C 1 -C 4 -alkyl-OR 31 , C 1 -C 4 -alkyl-SR 32 , C 1 -C 4 -alkyl-NR 33 R 34 , C 1 -C 6 -alkoxy, OC 1 -C 4 -alkyl-OR 31 , OC 1 -C 4 -alkyl-SR 32 , OC 1 -C 4 -alkyl-NR 33 R 34 , C 2 -C 6 -alkenyloxy, C 1 -C 6 -fluoroalkyl, C 1 -C 6 -fluoroalkoxy, C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, where the cycloalkyl moiety in the last two radicals is unsubstituted, partially or completely fluorinated, or substituted by 1, 2 or 3 methyl groups; 
         R 11 , R 12  independently of each other are selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, where R 11  may also be C 1 -C 4 -alkylsulfonyl and C 1 -C 4 -fluoroalkylsulfonyl; 
         R 13 , R 14  independently of each other are selected from the group consisting of hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl, or
 R 13  and R 14  together with the N atom to which they are attached form a 3- to 7-membered, nitrogen heterocycle which may have 1, 2 or 3 further different or identical heteroatoms or heteroatom containing groups selected from the group of O, N, S, SO and SO 2  as ring members and which may carry 1, 2, 3, 4, 5 or 6 substituents selected from C 1 -C 4 -alkyl and fluorine; 
 
         R 21 , R 22 , R 31  and R 32  have one of the meanings given for R 11 , R 12 ; 
         R 23 , R 24 , R 33  and R 34  have one of the meanings given for R 13 , R 14 ; 
         R 25  is selected from the group consisting hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl; and 
         R′ is hydrogen, hydrogen, C 1 -C 4 -alkyl, C 1 -C 4 -fluoroalkyl, C 3 -C 6 -cycloalkyl and C 3 -C 6 -cycloalkyl-C 1 -C 4 -alkyl. 
         and the N-oxides, the prodrugs, the tautomers and the hydrates thereof, and the pharmaceutically acceptable salts thereof. 
       
     
     
         2 . The compound of  claim 1 , where both Y 1  and Y 2  in Het 1  are carbon atoms. 
     
     
         3 . The compound of  claim 1 , where Het 1  is a bivalent monocyclic 5-membered heteroaromatic radical, having 1 heteroatom or heteroatom moiety selected from O, S and N—R a  as ring member, and 0, 1 or 2 further nitrogen atoms as ring members. 
     
     
         4 . The compound of  claim 3 , where Het 1  is selected from the group consisting of 1-(R a )-1H-pyrazole-3,4-diyl, 1-(R a )-1H-pyrazole-4,5-diyl, 1H-pyrazole-1,5-diyl, 1-(R a )-1H-imidazol-4,5-diyl, isoxazol-4,5-diyl, isoxazol-3,4-diyl, 1-(R a )-1H-1,2,3-triazol-4,5-diyl, 1H-oxazol-4,5-diyl, 1H-imidazol-1,2-diyl, 1H-imidazol-1,5-diyl and 1H-1,3,4-triazol-1,2-diyl and where k is 0 or 1. 
     
     
         5 . The compound of  claim 1 , where k in formula I is 0. 
     
     
         6 . The compound of  claim 1 , where in formula I the moiety of the formula Het1/2 
       
         
           
           
               
               
           
         
         is selected from the following radicals Het1/2a to Het1/2q: 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       where R a  is as defined in  claim 1  and where R b  is hydrogen or has one of the meanings given for R. 
     
     
         7 . The compound of  claim 6 , where Het1/2 is a radical Het1/2a. 
     
     
         8 . The compound of  claim 6 , where R b  in radicals Het1/2a to Het1/2q is hydrogen. 
     
     
         9 . The compound of  claim 1 , where Ar is a radical of the following formula, 
       
         
           
           
               
               
           
         
         X 1  is N or C—R x1 ; 
         X is N or C—R x2 ; 
         X is N or C—R x3 ; 
         X 4  is N or C—R x4 ; 
         provided that 0, 1 or 2 of X 1 , X 2 , X 3  and X 4  are N; 
         and where R x1 , R x2 , R x3 , R x4 , independently of each other, are hydrogen or have one of the meanings given for R 3 . 
       
     
     
         10 . The compound of  claim 9 , where X 1  is C—R x1 , X 2  is C—R x2 , X 3  is C—R x3  and X 4  is C—R x4 , where R x1 , R x2 , R x3 , R x4 , independently of each other, are hydrogen or have one of the meanings given for R 3 , and where in particular at least 3 of R x1 , R x2 , R x3  and R x4  are hydrogen and at most one of R x1 , R x2 , R x3  and R x4  is a radical R 3 . 
     
     
         11 . The compound of  claim 9 , where each X 1 , X 2 , X 3  and X 4  is CH. 
     
     
         12 . The compound of  claim 1 , which is of formula I-A: 
       
         
           
           
               
               
           
         
         the N-oxides, the prodrugs, the tautomers and the hydrates thereof, and the pharmaceutically acceptable salts thereof, 
         where Cyc, X 1 , X 2 , X 3 , X 4 , Het 2  and R a  are as defined in any one of the preceding claims. 
       
     
     
         13 . The compound of  claim 1 , which is of formula I-A.a: 
       
         
           
           
               
               
           
         
         the N-oxides, the prodrugs, the tautomers and the hydrates thereof, and the pharmaceutically acceptable salts thereof, 
         where Cyc, Het 2  and R a  are as defined in any one of the preceding claims. 
       
     
     
         14 . The compound of  claim 1 , where R a , if present, is selected from the group consisting of C 1 -C 4 -alkyl and C 1 -C 4 -fluoroalkyl. 
     
     
         15 . The compound of  claim 1 , where Het 2  is phenyl or a 5- or 6-membered monocyclic hetaryl, which has one heteroatom, selected from O, S and N as ring member and optionally one or two further heteroatoms or heteroatom moieties selected from O, S, N and N—R 1a  as ring members, where phenyl and the 5- or 6 membered hetaryl are unsubstituted or carry, independently of each other, 1, 2 or 3, radicals R 1 . 
     
     
         16 . The compound of  claim 1 , where Het 2  is selected from the group consisting of phenyl, oxazolyl, isoxazolyl, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl and pyridazinyl, where the aforementioned radicals are unsubstituted or may carry 1, 2 or 3 radicals R 1  and where R 1  is in particular selected from the group consisting of fluorine, chlorine, CN, methyl, difluoromethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy and NH 2 . 
     
     
         17 . The compound of  claim 1 , where Het 2  is 4-pyridyl. 
     
     
         18 . The compound of  claim 1 , which is of formula I-A.a′: 
       
         
           
           
               
               
           
         
         the N-oxides, the prodrugs, the tautomers and the hydrates thereof, and the pharmaceutically acceptable salts thereof, 
         where Cyc and R a  are as defined in any one of the preceding claims. 
       
     
     
         19 . The compound of  claim 1 , where Cyc is selected from the group consisting of C-bound 5- or 6-membered monocyclic hetaryl, which has 1 or 2 nitrogen atoms as ring members, benzofuryl and C-bound, 9- or 10-membered fused bicyclic hetaryl, which has 1 or 2 nitrogen atoms as ring members and optionally a further heteroatom selected from O, S and N as ring member;
 where monocyclic hetaryl, benzofuryl and bicyclic hetaryl may be unsubstituted or may carry 1, 2, 3 or 4 substituents R 2 .   
     
     
         20 . The compound of  claim 17 , where Cyc has at least one imino-nitrogen as ring member, which is located in the position adjacent to the carbon atom which is bound to the triple bond. 
     
     
         21 . The compound of  claim 18 , where Cyc is selected from the group consisting of 2-pyridyl, 2-pyrimidinyl, 4-pyrimidinyl, 2-pyrazinyl, 3-pyridazinyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 2-thiazolyl, 4-thiazolyl, 2-quinolinyl, 3-isoquinolinyl, 2-quinazolinyl, 2-quinoxalinyl, 1,5-naphthyridin-2-yl, 1,8-naphthyridin-2-yl, benzothiazol-1-yl, benzoxazol-1-yl, benzimidazol-2-yl, 1-methylbenzimidazol-2-yl, imidazo[1,2-a]pyridine-2-yl, pyrrolo[2,3-b]pyridine-6-yl, thieno[3,2-b]pyridine-5-yl, imidazo-[2,1-b]-thiazol-6-yl and 1,2,4-triazolo[1,5-a]pyridine-2-yl, where the aforementioned radicals may carry 1, 2 or 3 radicals selected from fluorine, chlorine, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, cyclopropyl, optionally substituted by 1, 2 or 3 methyl groups, and fluorinated cyclopropyl. 
     
     
         22 . The compound of  claim 1 , which is selected from the group consisting of
 4-(1-methyl-3-(4-((1-methyl-1H-imidazol-5-yl)ethynyl)phenyl)-1H-pyrazole-4-yl)pyridine,   2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenyl)ethynyl)pyridine,   5-methyl-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenyl)ethynyl)pyridine,   4-(1-methyl-3-(4-((1-propyl-1H-pyrazol-4-yl)ethynyl)phenyl)-1H-pyrazole-4-yl)pyridine,   5-fluoro-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenyl)ethynyl)pyridine,   3-methyl-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenyl)ethynyl)pyridine,   4-(1-methyl-3-(4-((1-methyl-1H-imidazol-2-yl)ethynyl)phenyl)-1H-pyrazole-4-yl)pyridine,   4-methyl-2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenyl)ethynyl)pyridine,   2-methyl-6-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenyl)ethynyl)pyridine,   4-(1-methyl-3-(4-((1-methyl-1H-pyrazol-4-yl)ethynyl)phenyl)-1H-pyrazole-4-yl)pyridine,   4-(3-(4-((1H-pyrazol-4-yl)ethynyl)phenyl)-1-methyl-1H-pyrazole-4-yl)pyridine,   2-((4-(1-methyl-4-(pyridin-4-yl)-1H-pyrazol-3-yl)phenyl)ethynyl)quinoline,   2-[2-[4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]-1,5-naphthyridine,   2-[2-[4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]imidazo[1,2-a]pyridine,   6-[2-[4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]-1H-pyrrolo[2,3-b]pyridine,   4-methyl-2-[2-[4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]quinoline,   2-[2-[4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]thiazole,   2-[2-[4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]quinoxaline,   3-[2-(6-methyl-2-pyridyl)ethynyl]-2-(4-pyridyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole,   2-methoxy-6-[2-[4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]pyridine,   3-methoxy-2-[2-[4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]pyridine,   4-[1-methyl-3-[4-(2-phenylethynyl)phenyl]pyrazol-4-yl]pyridine,   3-[4-[2-(6-methyl-2-pyridyl)ethynyl]phenyl]-2-(4-pyridyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole,   5-[1-methyl-3-[4-[2-(6-methyl-2-pyridyl)ethynyl]phenyl]pyrazol-4-yl]pyrimidine,   2-methyl-6-[2-[4-[1-methyl-4-(1H-pyrazol-4-yl)pyrazol-3-yl]phenyl]ethynyl]pyridine,   2-methyl-6-[2-[4-[2-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]pyridine,   2-methyl-6-[2-[4-[1-methyl-4-(2-methylpyrazol-3-yl)pyrazol-3-yl]phenyl]ethynyl]pyridine,   4-[1-methyl-3-[4-[2-(6-methyl-2-pyridyl)ethynyl]phenyl]pyrazol-4-yl]pyridazine,   2-methyl-6-[2-[4-[1-methyl-4-(3-pyridyl)pyrazol-3-yl]phenyl]ethynyl]pyridine,   2-[2-[4-[4-(4-fluorophenyl)-1-methyl-pyrazol-3-yl]phenyl]ethynyl]-6-methyl-pyridine,   2-[2-[4-[4-(4-methoxyphenyl)-1-methyl-pyrazol-3-yl]phenyl]ethynyl]-6-methyl-pyridine,   2-[2-[2-methoxy-4-[1-methyl-4-(4-pyridyl)pyrazol-3-yl]phenyl]ethynyl]-6-methyl-pyridine,   and the N-oxides, the prodrugs, the tautomers and the hydrates thereof, and the pharmaceutically acceptable salts thereof.   
     
     
         23 . The compound of  claim 1  for use in therapy. 
     
     
         24 . A pharmaceutical composition which comprises at least one compound as claimed in  claim 1  and at least one excipient. 
     
     
         25 . The compound of any  claim 1  for treating a medical disorder, selected from neurological and psychiatric disorders which can be treated by inhibition of phosphodiesterase type 10A. 
     
     
         26 . The compound of  claim 1  for treating CNS disorders in a mammalian. 
     
     
         27 . The compound of  claim 1  for treating schizophrenia in a mammalian. 
     
     
         28 . The compound of  claim 1  for treating cognitive dysfunction associated with schizophrenia in a mammalian. 
     
     
         29 . The compound of  claim 1  for treating bipolar disorders in a mammalian. 
     
     
         30 . The compound of  claim 1  for treating depression in a mammalian. 
     
     
         31 . The compound of  claim 1  for treating cognitive dysfunction associated with Alzheimer's disease in a mammalian. 
     
     
         32 . The compound of  claim 1  for treating diet-induced obesity in a mammalian. 
     
     
         33 . The compound of  claim 1  for treating Huntington's disease in a mammalian. 
     
     
         34 . The compound according to  claim 1  for treating anxiety in a mammalian. 
     
     
         35 . A method for treating a medical disorder, selected from neurological and psychiatric disorders which can be treated by inhibition of phosphodiesterase type 10A, said method comprising administering an effective amount of at least one compound as claimed in  claim 1  to a subject in need thereof. 
     
     
         36 . The compound of  claim 1  which comprises an isotope label. 
     
     
         37 . The compound of  claim 36 , which is a compound of formula I-A as described in  claim 12 , where the radical R 3  or the radical R a  comprises the isotope label. 
     
     
         38 . The compound of  claim 36 , which is a compound of formula I-A.a as described in  claim 13 , where the radical R 3  or the radical R a  comprises the isotope label. 
     
     
         39 . The compound of  claim 36 , which is a compound of formula I-A.a′, as described in  claim 18 , where the radical R 3  or the radical R a  comprises the isotope label. 
     
     
         40 . The compound of  claim 36 , where the isotope label is selected from a positron emitting isotope label, in particular from  11 C-label and  18 F-label, and a gamma ray emitting isotope, in particular  123 I. 
     
     
         41 . The compound of  claim 40 , wherein the compound is used in positron emission tomography or single photon emission computed tomography. 
     
     
         42 . The compound of  claim 40 , wherein the compound is used as a PDE10A ligand in positron emission tomography or single photon emission computed tomography of the brain.