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EP-3723754-B1 - IMIDAZO [1,2-C] QUINAZOLIN-5-AMINE COMPOUNDS WITH A2A ANTAGONIST PROPERTIES

EP3723754B1EP 3723754 B1EP3723754 B1EP 3723754B1EP-3723754-B1

Inventors

  • ALI, AMJAD
  • WU, HEPING
  • WANG, HONGWU
  • LIM, YEON-HEE
  • GALLO-ETIENNE, Gioconda, V.
  • KELLY, Joseph, Michael
  • BERLIN, MICHAEL
  • TING, PAULINE
  • TAGAT, JAYARAM, R.
  • XIAO, DONG
  • KUANG, RONGZE

Dates

Publication Date
20260513
Application Date
20181210

Claims (9)

  1. A compound, or a pharmaceutically acceptable salt thereof, of Formula I: wherein: R 1 is selected independently for each occurrence from: (1) R 1a 3 C-O-, wherein R 1a is -H or -F; (2) fluoro; (3) bromo; (4) morpholino; (5) a moiety of the formula: (6) a moiety of the formula: wherein, both of R 1 are either -H or methyl; (7) a moiety of the formula: and Z' is: (1) (2) wherein: (A) X 10 is -CH=, R 8a is present and is a bond from any available ring carbon to the 2- position of the imidazo[1,2-c]quinazolin-5-amine portion of the structure of Formula I, and R 8b is: or (B) X 10 is selected from =CH- or =N-, R 8b is a bond to the 2- position of the imidazo[1,2-c]quinazolin-5-amine portion of the structure of Formula I and R 8a is not present; or (3) wherein R 3c is: (A) -H; (B) -C(O)-R 3d , wherein R 3d is: (i) -CRF3; (ii) -CH3; or (iii) wherein: x 2 is 0, 1 or 2, and R 3e , if present, is (C) (ai) -CN; or (aii) -F; or wherein: x 3 is 0, 1 or 2 and R 3f is: (i) -CH 3 ; (ii) bonded via any available ring carbon, wherein R 3g , if present, is -CN; or (iii) aryl; (4) wherein R 4 is: (A) wherein R 4a , if present, is (i) -CF 3 ; (ii) -O-CF 3 ; (iii) -O-CH 3 ; or (iv) (B) -CH 2 -O-C(O)-CH 3 ; (C) or (D) (5) wherein R 3 is: (A) (B) -N(R 5b ) 2 , wherein R 5b is independently for each occurrence: (i) -H; (ii) linear, branched or cyclic alkyl of up to 6 carbon atoms, which is optionally substituted on one or more carbon atoms thereof with: (a) pyridine, which may be optionally substituted with methyl or bromine; (b) morpholine, bonded via the ring nitrogen; or (c) pyridine, which may optionally be substituted on a ring carbon thereof with one or more of (bi) halogen; or (bii) linear or branched alkyl of up to 4 carbon atoms; (iii) (iv) a moiety of the formula: wherein R 5c is: (a) (b) a moiety of the formula: wherein R 5d is: (ai) -H; (aii) -(CH 2 ) 3 -OH; (aiii) -C(O)-C(R 5da ) 3 ;, wherein R 5da is independently for each occurrence -H or -CH 3 ; (aiv) pyridine; or (av) a moiety of the formula: , wherein x 4 is 0, 1, or, 2, and, if present, R 5e is independently for each occurrence: -F; -O-(CH 2 ) 2 -O-CH 3 ; or -C(O)-O-C(CH 3 ) 3 ; or (c) or (v) (C) wherein R 5f , if present, is independently for each occurrance: (i) halogen; (ii) -NH-C(O)-R 5n , wherein R 5n is -CH 3 or pyridine; (iii) a moiety of the formula: wherein R 5g is a moiety of the formula: whrein X 1 is -N=, or -CH= and if present R 5h is independently for each occurrence -F; (iv) (v) or (vi) (D) wherein x 5 is 0, 1 or 2, and wherein R 5i , if present, is independently for each occurance: (i) halogen; (ii) -OCH 3 ; (iii) linear or branched alkyl of up to 6 carbon atoms, wherein said alkyl is optionally substituted on one or more carbons thereof with one or more substituents which are selected from : (a) -F; (b) -CF 3 ; (c) -OH; (d) -C(O)-N(R 5j ) 2 , wherein R 5j is independently for each occurrence -H, -CH 2 -CH 3 ; or (e) -C(O)-O-CH 3 ; and wherein, when x=2 and both R 5i are bonded to the same carbon atom, the two R 5i may be taken together with the cycloamine to which they are bonded to form: (E) a carbonyl group, thereby providing a moiety of the formula: wherein one of x 6 and y 6 is 0 or 1 and the other is 1 or 2; (F) an azaspirocycloalkyl moiety of the formula: wherein x 8a and x 8b are independently 0, 1, or 2 and the sum of x 8a and x 8b is 4 or less; (G) an oxa-azaspiro moiety or diazaspiro moiety of the formula: wherein, x 7 = 1 or 2, y 7 = 0 or 1, and x 7 +y 7 ≥ 1, and Q-Q' is: (i) -O-(CH 2 ) 3 -; (ii) -O-CH 2 -CH 2 - C(CH 3 ) 2 - ; (iii) -(CH 2 -O-CH 2 ); (iii) -CH 2 -O-(CH 2 ) 2 -; (iv) -O-(CH 2 ) 4 -; (v) -O-(CH 2 ) 2 -O-; (vi) -(CH 2 ) 2 -C(O)-O-; (vii)-(C(R 7a ) 2 ) 2 -O-C(O)-, wherein R 7a is independently for each occurrence -H or-CH 3 ; or (viii) -(CH 2 ) 2 -Y 11 -(CH 2 ) 1 , 2 -, wherein, Y 11 is -N(R 5k )- or -N + (R 5k ) 2 -, and wherein R 5k is independently for each occurrence: (a) -H; (b) linear or branched alkyl of up to 4 carbon atoms; (c) (CH 3 ) 3 C-O-C(O)-; (d) CH 3 -C(O)-; (e) -(C(O)) 0,1 -(CH 2 ) 1,2 -aryl, wherein said aryl is optionally substituted with one or more substituents which are independently -F or -CN; or (avi) CH 3 -C(O)-; and wherein, when x=2 and each R 5i is bonded to a different carbon atom, including adjacent carbon atoms, both R 5i may be taken together with the cycloamine to which they are bonded, comprises a 5, 6, or 7 member cycloamine ring fused with or bridged by a 3, 4, 5, or 6-member alkyl ring thereby providing a fused-bicyclo structure or a bridged bicyclo structure wherein said two R 5i together have the formula: (H) (-CH 2 -) x9 wherein "x 9 " is 1, 2, 3, or 4; (I) [-(CH 2 ) 1,2 -O-]; (1) -CH 2 -SO 2 -CH 2 -; or (J) -CH 2 -O-CH 2 , and wherein, one or more carbon atoms in said moiety may optionally be substituted with an alkyl or alkoxy moiety comprising up to four carbon atoms; (K) wherein, if present, R 16d is independently for each occurrance a linear, branched or cyclic alkyl of up to 6 carbon atoms which is optionally substituted on one or more carbon atoms thereof with -F; (L) (M) wherein R1 is: (a) or (b) (N) a moiety of the formula: wherein X 1 is -N=, or - CH= and if present R 5g is independently for each occurrence -F or (6) wherein: R 6a1 and R 6a2 are both 1 or both 2, and each R 6 is independently: (A) -H; (B) -OH; (C) -CH 3 ; (D) aryl which is optionally substituted on one or more ring carbon atoms with chlorine; or (E) -CH 2 -aryl; (7) wherein R 7 is: (A) CH 2 -CH 3 ; (B) wherein, if present, R 7a is independently for each occurrence from; (i) -F; or (ii) or (C) (8) (9) wherein, X 4 is -N= or -CH=, if present) R 8 is independently for each occurrence: (A) a halogen; (B) pyrimidine, which is bonded via one of carbon positions 2, 4, 5 or 6; (C) aryl, which is optionally substituted with one or two -F; (D) -NH-C(O)- R 8a , wherein R 8a is: (i) -CH 3 ; or (ii) pyridine; or (E) -CH 2 -C(O)-NH-R 8a , wherein R 8a is: (i) -CH 3 ; or (ii) pyridine; and A 1 is a moiety bonded between two adjacent ring carbons which is of the formula selected from: (A) (B) (C) (D) or (E) (10) or (11) wherein R 9 is: (A) -H; (B) (C) wherein, if present, R 9b is -OCH 3 or -CH 3 ; (D) (E) (F) , wherein, Y 10 is -CH= or -N=, and if present, R 9c is --CH 3 , methoxy, -F, or -Br; (G) -CH 2 R 9a , wherein R 9a is (i) a linear, branched or cyclic alkyl of up to 4 carbon atoms; or (ii) a cyclic alkyl comprising an alkyl ring of up to 5 carbon atoms; (H) wherein, one of Y 9a and Y 9b is -CH= and the other is -N=; or (I) (12) wherein: X 11 is -O- or -N(R 11a )-, wherein R 11a is (A) aryl which is optionally substituted with one or two of (i) -F; (ii) -Cl; or (iii) -OH; or (B) pyridine; or (13)
  2. A compound of Claim 1, or a pharmaceutical salt thereof, wherein R 1 is selected to be 7-methoxy providing the structure: and wherein Z' is as defined above.
  3. A compound of Claim 1, or a pharmaceutical salt thereof, wherein R 1 is selected to be 7-fluoro, providing the structure: and wherein Z' is as defined above.
  4. A compound of claim 1, or a pharmaceutically acceptable salt thereof, selected from: 2-(quinolin-8-ylmethyl)imidazo[1,2-c]quinazolin-5-amine; 7-methoxy-2-(quinolin-8-ylmethyl)imidazo[1,2-c]quinazolin-5-amine; 2-((5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)methyl)-3-fluorophenol; 7-fluoro-2-(quinolin-8-ylmethyl)imidazo[1,2-c]quinazolin-5-amine; 2-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-4-fluorophenol; 1-(6-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one; 1-(7-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one; 7-methoxy-2-((2-(pyrrolidin-1-yl)pyridin-3-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-methoxy-2-((2-(piperidin-1-yl)pyridin-3-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-methoxy-2-((2-(4-methylpiperazin-1-yl)pyridin-3-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)imidazo-[1,2-c]quinazolin-5-amine; 1-(5-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one; 6-(5-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)nicotinonitrile; 3-(2-(5-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl)benzonitrile; 7-fluoro-2-((2-propyl-1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)imidazo-[1,2-c]quinazolin-5-amine; 7-fluoro-2-((2-(2-(pyridin-2-yl)ethyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((2-(pyridin-2-ylmethyl)-1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 1-(5-((5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)-2-(3,4-difluorophenyl)ethan-1-one; 1-(5-((5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)methyl)-3,4-dihydroisoquinolin-2(1H)-yl)-4,4,4-trifluorobutan-1-one; 2-((2-benzylisoindolin-5-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 1-(8-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-2,3-dihydro-4H-benzo[b] [1,4]oxazin-4-yl)-2-(pyridin-2-yl)ethan-1-one; 7-methoxy-2-((4-(4-methoxyphenyl)-1H-1,2,3-triazol-1-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((4-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((4-(4-(trifluoromethoxy)-phenyl)-1H-1,2,3-triazol-1-yl)methyl)-imidazo[1,2-c]-quinazolin-5-amine; 7-fluoro-2-((4-(pyridin-3-yl)-1H-1,2,3-triazol-1-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((4-(2-(4-(4-methoxyphenyl)piperazin-1-yl)ethyl)-1H-1,2,3-triazol-1-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((4-(4-(pyridin-3-yl)phenyl)-1H-1,2,3-triazol-1-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; (1-((5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)methyl)-1H-1,2,3-triazol-4-yl)methyl acetate; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(phenyl)methanone; 1-((5-aminoimidazo[1,2-c]quinazolin-2-yl)methyl)-4-methylpiperidin-4-ol; 7-methoxy-2-((4-phenylpiperazin-1-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((4-benzylpiperazin-1-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 2-((4-ethylpiperazin-1-yl)methyl)-7-fluoroimidazo[1,2-c] quinazolin-5-amine; 7-fluoro-2-((4-phenethylpiperazin-1-yl)methyl)imidazo-[1,2-c]quinazolin-5-amine; 2-((4-benzylpiperidin-1-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-(morpholinomethyl)imidazo[1,2-c]quinazolin-5-amine; 2-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((2,3-dihydro-4H-benzo[b][1,4]oxazin-4-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 2-((2,3-dihydro-4H-pyrido[3,2-b][1,4] oxazin-4-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((4-(pyridin-2-yl)-1,4-diazepan-1-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((5,8-dihydro-1,7-naphthyridin-7(6H)-yl)methyl)-7-methoxyimidazo[1,2-c]quinazolin-5-amine; 2-((3,4-dihydroisoquinolin-2(1H)-yl)methyl)-7-methoxyimidazo[1,2-c]quinazolin-5-amine; 2-((5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)methyl)-7-methoxyimidazo[1,2-c]quinazolin-5-amine; 2-((5-fluoroisoindolin-2-yl)methyl)-7-methoxyimidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((5-fluoroisoindolin-2-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((6-bromo-3,4-dihydroquinolin-1(2H)-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 2-((5-bromoisoindolin-2-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; N-(2-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)picolinamide; N-(2-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)acetamide; 2-(2-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)-N-(pyridin-2-yl)acetamide; 2-((6-(3,4-difluorophenyl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 2-(2-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)-N-(pyridin-2-yl)acetamide; (R)-7-methoxy-2-((octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((6-(pyrimidin-5-yl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-methoxy-2-((7-(pyrimidin-5-yl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((7-(3,4-difluorophenyl)-3,4-dihydroisoquinolin-2(1H)-yl)methyl)-7-methoxyimidazo[1,2-c]quinazolin-5-amine; 1-(4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)-3,4-dihydroquinoxalin-1(2H)-yl)-2-(pyridin-2-yl)ethan-1-one; 2-(2-(5,7-dihydro-6H-pyrrolo[3,4-b]pyridin-6-yl)ethyl)-7-methoxyimidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-(2-(4-(pyridin-2-yl)piperazin-1-yl)ethyl)imidazo[1,2-c]quinazolin-5-amine; 7-bromo-2-((phenylamino)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((benzylamino)methyl)-7-bromolmidazo[1,2-c]quinazolin-5-amine; 7-bromo-2-(((pyridin-3-ylmethyl)amino)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-(((4-fluorobenzyl)amino)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((benzylamino)-methyl)-7-methoxy-imidazo[1,2-c]-quinazolin-5-amine; 2-((3-(3-chlorophenyl)azetidin-1-yl)methyl)-7-methoxyimidazo[1,2-c]quinazolin-5-amine; 7-methoxy-2-(((pyridin-3-ylmethyl)amino)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-(phenoxymethyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((3-methoxyphenoxy)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-(1-ethyl-1H-pyrazol-4-yl)-2-(((4-fluorobenzyl)amino)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-benzyl-7-(1-ethyl-1H-pyrazol-4-yl)imidazo[1,2-c]quinazolin-5-amine; 2-(((3-chlorobenzyl)-(methyl)amino)-methyl)-7-(1-ethyl-1H-pyrazol-4-yl)imidazo[1,2-c]-quinazolin-5-amine; 2-benzyl-7-(3,5-dimethylisoxazol-4-yl)imidazo[1,2-c]quinazolin-5-amine; 2-((benzylamino)-methyl)-7-(3,5-dimethyl-isoxazol-4-yl)-imidazo[1,2-c]-quinazolin-5-amine; 5-amino-7-methoxy-N-(quinolin-8-ylmethyl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-N-(2,4-difluorobenzyl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-7-methoxy-N-methyl-N-(quinolin-8-ylmethyl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-N-methyl-N-(quinolin-8-ylmethyl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-N-(quinolin-8-ylmethyl)-imidazo-[1,2-c]-quinazoline-2-carboxamide; 5-amino-7-fluoro-N-methyl-N-(quinolin-8-ylmethyl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-7-fluoro-N-(quinolin-8-ylmethyl)imidazo[1,2-c]quinazoline-2-carboxamide; (5-bromoisoindolin-2-yl)(5-((2,4-dimethoxybenzyl)amino)-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methanone; (5-aminoimidazo[1,2-c]quinazolin-2-yl)(4-(2,4-difluorophenyl)piperazin-1-yl)methanone; 5-amino-7-fluoro-N-(2-morpholino-2-(pyridin-3-yl)ethyl)imidazo[1,2-c]quinazoline-2-carboxamide; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3,5-dimethylpiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(4,4-difluoropiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-methoxypiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-methylpiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-fluoropiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3,3-difluoropiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-(trifluoromethyl)piperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(5-azaspiro[2.5]octan-5-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)((3R,4R)-3,4-difluoropyrrolidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(4-methylazepan-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(1,4-oxazepan-4-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(4,4-difluoroazepan-1-yl)methanone; 1-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)azepan-4-one; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)((2R,6S)-2,6-dimethylmorpholino)methanone; (R)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-methylmorpholino)methanone; (S)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-methylmorpholino)methanone; (R)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-methylmorpholino)methanone; (S)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-methylmorpholino)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-(trifluoromethyl)morpholino)-methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-isobutylmorpholino)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2,2-dimethylmorpholino)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(1,4-dioxa-8-azaspiro[4.5]decan-8-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3,3-dimethylpiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[ 1,2-c]quinazolin-2-yl)(piperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-(hydroxymethyl)piperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(octahydroisoquinolin-2(1H)-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(4-methylpiperidin-1-yl)methanone; 1-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)-N,N-diethylpiperidine-3-carboxamide; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-methylpiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(4-isopropylpiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-oxa-8-azaspiro[4.5]decan-8-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(4-azaspiro[2.5]octan-4-yl)methanone; 1-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)-3-isopropylpiperidin-4-one; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(6-azaspiro[3.5]nonan-6-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(6-azaspiro[2.5]octan-6-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(8-azaspiro[4.5]decan-8-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-oxa-6-azaspiro[3.5]nonan-6-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(1-oxa-8-azaspiro[5.5]undecan-8-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(1-oxa-7-azaspiro[4.5]decan-7-yl)methanone; (5-amino-7-methoxyimidazo[ 1,2-c] quinazolin-2-yl)(2-oxa-7-azaspiro[3.5]nonan-7-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(4,4-dimethylpiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-y1)(8-azabicyclo[3.2.1]octan-8-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-isopropylpyrrolidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2,5-dimethylpyrrolidin-1-yl)methanone; (S)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-(trifluoromethyl)pyrrolidin-1-yl)methanone; (S)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-methoxypyrrolidin-1-yl)methanone; (R)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-methoxypyrrolidin-1-yl)methanone; (R)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-(fluoromethyl)pyrrolidin-1-yl)methanone; (S)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-fluoropyrrolidin-1-yl)methanone; (S)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-methylpyrrolidin-1-yl)methanone; (R)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-(trifluoromethyl)pyrrolidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)((1s,4s)-7-azabicyclo[2.2.1]heptan-7-yl)methanone; (S)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-(fluoromethyl)pyrrolidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(hexahydro-4H-furo[3,2-b]pyrrol-4-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3,3-difluoropyrrolidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2-azaspiro[4.4]nonan-2-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(2,2,6,6-tetramethylmorpholino)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methanone; methyl 1-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)piperidine-4-carboxylate; 8-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)-1-oxa-8-azaspiro[4.5]decan-2-one; 8-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)-2-oxa-8-azaspiro[4.5]decan-1-one; 7-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)-3,3-dimethyl-2-oxa-7-azaspiro[4.5]decan-1-one; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(1-oxa-8-azaspiro[4.5]decan-8-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(1,4-dioxa-7-azaspiro[4.5]decan-7-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3,3-dimethoxypiperidin-1-yl)methanone; 7-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)-2-oxa-7-azaspiro[4.5]decan-1-one; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(4,4-dimethyl-1-oxa-8-azaspiro[4.5]decan-8-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-azabicyclo[3.1.0]hexan-3-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)((3aR,4R,7S,7aS)-octahydro-2H-4,7-methanoisoindol-2-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3,3-dioxido-3-thia-6-azabicyclo[3.2.1]octan-6-yl)methanone; 1-(5-amino-7-methoxyimidazo[1,2-c]quinazoline-2-carbonyl)pyrrolidin-3-one; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)((2R,6R)-2,6-dimethylmorpholino)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-methoxypiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3,3-difluoropiperidin-1-yl)methanone; (5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(5-azaspiro[2.5]octan-5-yl)methanone; (S)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(3-(fluoromethyl)pyrrolidin-1-yl)methanone; N-(2-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)acetamide; (R)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)methanone; 5-amino-7-fluoro-N-(2-((4-(pyridin-2-yl)piperazin-1-yl)methyl)benzyl)imidazo[1,2-c]quinazoline-2-carboxamide; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(8-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)-3,4-dihy droisoquinolin-2(1H)-yl)methanone; 5-amino-7-fluoro-N-(1,2,3,4-tetrahydroquinolin-4-yl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-N-(2-((4-(2,4-difluorophenyl)piperazin-1-yl)methyl)benzyl)-7-fluoroimidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-7-fluoro-N-(2-morpholinobenzyl)imidazo[1,2-c]quinazoline-2-carboxamide; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(8-((4-(pyridin-2-yl)piperazin-1-yl)methyl)-3,4-dihy droisoquinolin-2(1H)-yl)methanone; 5-amino-N-(3-(4-(2,4-difluorophenyl)piperazin-1-yl)benzyl)-7-fluoroimidazo[1,2-c] quinazoline-2-carboxamide; 5-amino-7-fluoro-N-(2-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)benzyl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-7-fluoro-N-(3-(4-(4-(2-methoxyethoxy)phenyl)piperazin-1-yl)benzyl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-7-fluoro-N-(2-(morpholinomethyl)benzyl)imidazo[1,2-c]quinazoline-2-carboxamide; tert-butyl 4-(2-((5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carboxamido)methyl)phenyl)piperazine-1-carboxylate; 5-amino-7-fluoro-N-(3-morpholino-benzyl)imidazo-[1,2-c]-quinazoline-2-carboxamide; 5-amino-7-fluoro-N-(3-(morpholinomethyl)benzyl)imidazo[1,2-c]quinazoline-2-carboxamide; tert-butyl 7-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,7-diazaspiro[4.4]nonane-2-carboxylate; tert-butyl 7-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,7-diazaspiro[4.5]decane-2-carboxylate; 5-amino-7-fluoro-N-(2-(piperazin-1-yl)benzyl)imidazo[1,2-c]quinazoline-2-carboxamide; tert-butyl 8-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,8-diazaspiro[4.5]decane-2-carboxylate; 5-amino-7-fluoro-N-(2-((1-(pyridin-2-yl)piperidin-4-yl)oxy)benzyl)imidazo[1,2-c]quinazoline-2-carboxamide; N-(2-(4-acetylpiperazin-1-yl)benzyl)-5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carboxamide; tert-butyl 9-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,9-diazaspiro[5.5]undecane-2-carboxylate; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(2,7-diazaspiro[4.5]decan-7-yl)methanone; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(2,8-diazaspiro[4.5]decan-8-yl)methanone; 1-(7-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,7-diazaspiro[4.5]decan-2-yl)ethan-1-one; 1-(8-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,8-diazaspiro[4.5]decan-2-yl)ethan-1-one; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(2,9-diazaspiro[5.5]undecan-9-yl)methanone; 5-amino-7-fluoro-N-(2-(4-(3-hydroxypropyl)piperazin-1-yl)benzyl)imidazo[1,2-c]quinazoline-2-carboxamide; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(2,7-diazaspiro[4.4]nonan-2-yl)methanone; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(7-(4-fluorobenzyl)-2,7-diazaspiro[4.4]nonan-2-yl)methanone; 1-(7-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,7-diazaspiro[4.4]nonan-2-yl)ethan-1-one; 4-(7-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,7-diazaspiro[4.4]nonan-2-yl)-3-fluorobenzonitrile; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(2-propyl-2,7-diazaspiro[4.5]decan-7-yl)methanone; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(2-propyl-2,8-diazaspiro[4.5]decan-8-yl)methanone; 1-(9-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,9-diazaspiro[5.5]undecan-2-yl)ethan-1-one; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(2-propyl-2,9-diazaspiro[5.5]undecan-9-yl)methanone; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(7-ethyl-2,7-diazaspiro[4.4]nonan-2-yl)methanone; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(7-(4-fluorophenethyl)-2,7-diazaspiro[4.4]nonan-2-yl)methanone; 1-(7-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-2,7-diazaspiro[4.4]nonan-2-yl)-2-(3,4-difluorophenyl)ethan-1-one; 2-(2-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)-N-(pyridin-2-yl)acetamide; (R)-(5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)methanone; (S)-(5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)methanone; N-(2-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)picolinamide;; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(6-(pyrimidin-5-yl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone; N-(2-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-6-yl)acetamide; (5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)(6-(3,4-difluorophenyl)-3,4-dihydroisoquinolin-2(1H)-yl)methanone; 2-(2-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)-N-(pyridin-2-yl)acetamide; N-(2-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)picolinamide; N-(2-(5-amino-7-fluoroimidazo[1,2-c]quinazoline-2-carbonyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)acetamide; (R)-(5-amino-7-methoxyimidazo[1,2-c]quinazolin-2-yl)(octahydro-2H-pyrido[1,2-a]pyrazin-2-yl)methanone; 5-amino-N-((6-bromopyridin-2-yl)methyl)-7-fluoroimidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-7-fluoro-N-((6-methylpyridin-2-yl)methyl)imidazo[1,2-c]quinazoline-2-carboxamide; (S)-5-amino-7-fluoro-N-(1-phenylethyl)imidazo[1,2-c]quinazoline-2-carboxamide; (R)-5-amino-7-fluoro-N-(1-phenylethyl)imidazo[1,2-c]quinazoline-2-carboxamide; 5-amino-7-fluoro-N-(pyridin-2-ylmethyl)imidazo[1,2-c]quinazoline-2-carboxamide; 7-fluoro-2-(piperidin-4-ylmethyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((1-(5-fluoropyrimidin-2-yl)piperidin-4-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((1-(thiophen-2-ylmethyl)piperidin-4-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(pyridin-3-yl)methanone; 7-fluoro-2-(piperidin-4-ylmethyl)-imidazo-[1,2-c]quinazolin-5-amine; 2-((1-benzylpiperidin-4-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 2-((1-(cyclopropylmethyl)piperidin-4-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((1-(thiophen-2-ylmethyl)piperidin-4-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 2-((1-ethylpiperidin-4-yl)methyl)-7-fluoroimidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((1-phenethylpiperidin-4-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((1-(4-methoxybenzyl)piperidin-4-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((1-(3-methoxybenzyl)piperidin-4-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; 7-fluoro-2-((1-(2-methoxybenzyl)piperidin-4-yl)methyl)-imidazo[1,2-c]-quinazolin-5-amine; 7-fluoro-2-((1-(4-methylbenzyl)piperidin-4-yl)methyl)-imidazo-[1,2-c]-quinazolin-5-amine; 7-fluoro-2-((1-(pyridin-3-ylmethyl)piperidin-4-yl)methyl)imidazo[1,2-c]quinazolin-5-amine; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(phenyl)methanone; benzyl 4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidine-1-carboxylate; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(pyridin-3-yl)methanone; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(pyridin-2-yl)methanone; 5-amino-7-fluoro-2-((1-(5-fluoropyridin-2-yl)piperidin-4-yl)methyl)imidazo[1,2-c]quinazolin-6-ium 2,2,2-trifluoroacetate; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(4-methoxypyridin-2-yl)methanone; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(pyrazin-2-yl)methanone; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(6-bromopyridin-2-yl)methanone; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(5-fluoropyridin-2-yl)methanone; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(6-methylpyridin-2-yl)methanone; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(6-methoxypyridin-2-yl)methanone; (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(pyrimidin-2-yl)methanone; and (4-((5-amino-7-fluoroimidazo[1,2-c]quinazolin-2-yl)methyl)piperidin-1-yl)(5-methoxypyridin-2-yl)methanone.
  5. A pharmaceutical composition comprising any of the compounds of Claims 1 to 4, or a pharmaceutically acceptable salt thereof, and at least one excipient.
  6. A compound, or a pharmaceutically acceptable salt thereof, according to any of Claim 1 to 4 for use in therapy.
  7. A compound, or a pharmaceutically acceptable salt thereof according to any of Claims 1 to 4 for use in treating a central nervous system (CNS) disorder.
  8. A compound, or a pharmaceutically acceptable salt thereof according to any of Claims 1 to 4 for use in inhibiting adenosine signaling in tumor immunosuppression in the provision of immunotherapy for a turmor.
  9. A compound of any of Claims 1 to 4, or a pharmaceutically acceptable salt thereof for use in a method of treating tumors succeptible to anti-PD-1 therapy comprising coadministering anti-PD-1 therapy.

Description

BACKGROUND OF THE INVENTION Adenosine is known to be an endogenous modulator of a number of physiological functions. At the cardiovascular system level, adenosine is a strong vasodilator and a cardiac depressor. On the central nervous system, adenosine induces sedative, anxiolytic and antiepileptic effects. On the respiratory system, adenosine induces bronchoconstriction. At the kidney level, it exerts a biphasic action, inducing vasoconstriction at low concentrations and vasodilation at high doses. Adenosine acts as a lipolysis inhibitor on fat cells and as an anti-aggregant on platelets. Adenosine action is mediated by the interaction with different membrane specific receptors which belong to the family of receptors coupled with G proteins. Biochemical and pharmacological studies, together with advances in molecular biology, have allowed the identification of at least four subtypes of adenosine receptors: A1, A2A, A2b and A3. A1 and A3 are high-affinity, inhibiting the activity of the enzyme adenylate cyclase, and A2A and A2b are low-affinity, stimulating the activity of the same enzyme. Analogs of adenosine able to interact as antagonists with the A1, A2A, A2b and A3 receptors have also been identified. Compounds which are selective antagonists for the A2A receptor specifically are of pharmacological interest because of their reduced level of side effects over A2a antagonists which effect a broader range of adenosine receptors. In the central nervous system, A2A antagonists can have antidepressant properties and stimulate cognitive functions. Moreover, data has shown that A2A receptors are present in high density in the basal ganglia, known to be important in the control of movement. Hence, A2A antagonists can improve motor impairment due to neurodegenerative diseases, for example, Parkinson's disease, senile dementia as in Alzheimer's disease, and psychoses of organic origin. Some xanthine-related compounds have been found to be A1 receptor selective antagonists, and xanthine and non-xanthine compounds have been found to have high A2A affinity with varying degrees of A2A vs. A1 selectivity. Triazolo-pyrimidine adenosine A2A receptor antagonists with different substitution at the 7-position have been disclosed previously, for example in PCT International Application Publication Nos. WO 95/01356; US 5,565,460; WO 97/05138; and WO 98/52568. Parkinson's disease is characterized by progressive degeneration of the nigrostriatal dopaminergic pathway. The subsequent reduction in striatal dopamine levels is responsible for motor symptoms associated with Parkinson's disease, e.g., the loss of fine motor control or motor impairment manifested in those suffering from the disease. Current methodologies for alleviating motor symptoms associated with Parkinson's disease seek to replace dopamine either within the presynaptic terminal, for example, by administration of L-Dopa, directly through stimulation of the postsynaptic D2 receptors, or by inhibiting metabolism, for example, by administration of monoamine oxidase type B (MAO-B) or catechol-O-methyltransferase (COMT). Long term use of such therapies is often associated with adverse events. For example, long term therapy with L-Dopa (currently the standard of care) is often associated with adverse events (e.g. motor complications), for example, "wearing-off", "random on-off" oscillations, or dyskinesia. These motor complications arising from therapy administered to manage Parkinson's disease often become progressively more severe with continued treatment. As mentioned above, A2A receptors are present in high density in the basal ganglia and are known to be important in the control of fine motor movement. Highly selective A2A antagonists have demonstrated their efficacy in reducing motor symptoms associated with neurodegenerative diseases. Accordingly, compounds which are A2A receptor antagonists are believed to be useful in alleviating motor symptoms associated with Parkinson's disease. For example, U.S. Patent No. 6,630,475 to Neustadt et al. (the '475 patent) describes the preparation of the compound of Formula PI: In the '475 patent example Schemes 1 to 5, along with preparative Schemes 1 to 4, show general methods of preparing compounds of Formula PI. The '475 patent describes also that the compound of Formula I can be prepared as a pharmaceutically acceptable salt which may be useful for treating Parkinson's disease. The use of A2A receptor antagonists in the potential treatment of central nervous system diseases, in particular Parkinson's disease, and to pharmaceutical compositions comprising said compounds has elevated the need for potent, moderately lipophilic, brain penetrant inhibitors of the A2A receptor. Such compounds would provide an expansion of the arsenal of compounds which are believed to have value in the treatment of central nervous system disorders, in particular treating or managing the progression of such diseases, for example, but not limited