Thiazolopytimidines and their use as modulators of chemokine receptor activity

{
  "publication_number": "US2004157853A1",
  "country": "US",
  "kind": "A1",
  "title": "Thiazolopytimidines and their use as modulators of chemokine receptor activity",
  "abstract": "The invention provides certain thiazolopyrimidine compounds of formula (1) or a pharmaceutically acceptable salt or solvate thereof: in which: A is a group of formula (a) or (b): processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.",
  "claims": [
    "1. A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof: in which: A is a group of formula (a) or (b): R 1 represents a C 3 -C 7 carbocyclic, C 1 -C 8 alkyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl group, each of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, - OR 4, - NR 5 R 6, - CONR 5 R 6, - COOR 7, - NR 8 COR 9, - SR 10, - SO 2 R 10, - SO 2 NR 5 R 6, - NR 8 SO 2 R 9, an aryl or heteroaryl group, which last two may themselves be optionally substituted by one or more substituents independently selected from halogen atoms, cyano, nitro, - OR 4, - NR 5 R 6, - CONR 5 R 6, - COOR 7, - NR 8 COR 9, - SR 10, - SO 2 R 10, - SO 2 NR 5 R 6, - NR 8 SO 2 R 9, C 1 -C 6 alkyl or trifluoromethyl groups; R 2 and R 3 each independently represent a hydrogen atom, or a C 3 -C 7 carbocyclic, C 1 -C 8 allyl, C 2 -C 6 alkenyl or C 2 -C 6 alkynyl group, the latter four groups may be optionally substituted by one or more substituent groups independently selected from: (a) halogen atoms, - OR 4, - NR 5 R 6 - CONR 5 R 6, - COOR 7, - NR 8 COR 9, - SR 10, - SO 2 R 10, - SO 2 NR 5 R 6, - NR 8 SO 2 R 9; (b) a 3-8 membered ring optionally containing one or more atoms selected from O, S, NR 8 and itself optionally substituted by C 1 -C 3 -alkyl or halogen; or (c) an aryl group or heteroaryl group each of which may be optionally substituted by one or more substituents independently selected from halogen atoms, cyano, nitro, - OR 4, - NR 5 R 6, - CONR 5 R 6, - NR 8 COR 9, - SO 2 NR 5 R 6, - NR 8 SO 2 R 9, C 1 -C 6 alkyl and trifluoromethyl groups; R 4 represents hydrogen, C 1 -C 6 alkyl or a phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, - OR 11 and - NR 12 R 13 R 5 and R 6 independently represent a hydrogen atom or a C 1 -C 6 alkyl or phenyl group the latter two of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, - OR 14 and - NR 15 R 16, - CONR 15 R 16, - NR 15 COR 16, - SONR 15 R 16, NR15SO 2 R 16 or R 5 and R 6 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocyclic ring system optionally containing a further heteroatom selected from oxygen and nitrogen atoms, which ring system may be optionally substituted by one or more substituent groups independently selected from phenyl, - OR 14, - COOR 14, - NR 15 R 16, - CONR 15 R 16, - NR 15 COR 16, - SONR 15 R 16, NR 15 SO 2 R 16 or C 1 -C 6 alkyl, itself optionally substituted by one or more substituents independently selected from halogen atoms and - NR 15 R 16 and - OR 17 groups; R 10 represents a C 1 -C 6 -alkyl or a phenyl group, either of which may be optionally substituted by one or more substituent groups independently selected from halogen atoms, phenyl, - OR 17 and NR 15 R 16, X is CH or CCN, Y is N or CR 18, and each of R 7, R 8, R 9, R 11, R 12, R 13, R 14 R 15, R 16, R 17 and R 18 independently represents a hydrogen atom or a C 1 -C 6, alkyl, or a phenyl group. 2. A compound according to claim 1, wherein R 1 represents an optionally substituted benzyl group. 3. A compound according to claim 1 or claim 2, wherein one of R 2 and R 3 is hydrogen and the other is C 1 -C 8 alkyl substituted by hydroxy and one or more methyl or ethyl groups. 4. A compound according to any one of claims 1 to 3 in which A is a group of formula (a). 5. A compond according to any one of claims 1 to 3 in which A is a group of formula (b). 6. A compound according to claim 5 in which X is CH and Y is N. 7. A compound according to claim 1 selected from: - [[(2,3-difluorophenyl)methyl]thio]-7-[[(1R)-2-hydroxy-1-methylethyl]amino]-thiazolo[4,5-d]pyrimidine-2(3H)-thione, 2-[[(2,3-difluorophenyl)methyl]thio]-4-[[(1R)-2-hydroxy-1-methylethyl]amino]-7(8H)-pteridinethione, and pharmaceutically acceptable salts thereof. 8. A process for the preparation of a compound of formula (I) which comprises: (a) treatment of a compound of formula (IIA): where R 1, R 2 and R 3 are as defined in formula (I) or are protected derivatives thereof and L is a leaving group with a metal hydrosulphide, or (b) treatment of a compound of formula (IIB): where R 1, R 2 and R 3 are as defined in formula (I) or are protected derivatives thereof with a thiating agent, and optionally thereafter process (a) or (b) and in any order: removing any protecting groups forming a pharmaceutically acceptable salt. 9. A pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in association with a pharmaceutically acceptable adjuvant, diluent or carrier. 10. A process for the preparation of a pharmaceutical composition as claimed in claim 9 which comprises mixing a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 with a pharmaceutically acceptable adjuvant, diluent or carrier. 11. A compound of formula (I), or a pharmaceutically-acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 for use in therapy. 12. Use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7 in the manufacture of a medicament for use in therapy. 13. A method of treating a chemokine mediated disease wherein the chemokine binds to one or more chemokine receptors, which comprises administering to a patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7. 14. A method according to claim 13 in which the chemokine receptor belongs to the CXC chemokine receptor subfamily. 15. A method according to claim 13 or 14 in which the chemokine receptor is the CXCR2 receptor. 16. A method of treating an inflammatory disease in a patient suffering from, or at risk of, said disease, which comprises administering to the patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as claimed in any one of claims 1 to 7. 17. A method according to claim 16, wherein the disease is psoriasis, rheumatoid arthritis or COPD. 18. A method according to claim 16, wherein the disease is rheumatoid arthritis."
  ],
  "cpc": [
    "C07D 471/04",
    "A61P 11/00",
    "A61P 17/06",
    "A61P 19/02",
    "A61P 29/00",
    "A61P 43/00",
    "C07D 487/04",
    "C07D 513/04"
  ],
  "filing_date": "2002-04-12",
  "publication_date": "2004-08-12",
  "priority_date": "2001-04-12",
  "application_number": "US-47461003-A",
  "family_id": "20283779",
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}