| 摘要 |
Medicaments contain tetrahydro-pyrazolo (1,5-a) pyrimidine or 6,7-dihydro-5H-thiazolo (2,3-a) pyrimidine compounds (I) - (III). New medicaments contain pyrazolo- or thiazolo-pyrimidine compounds of formula (I) - (III) or their acid or base addition salts or solvates (specifically hydrates), in the form of racemates, pure stereoisomers (specifically enantiomers or diastereomers) or stereoisomer mixtures in any ratio. [Image] R1, R2H, OR9, SR10, 1-12C alkyl, cycloalkyl, cycloalkylmethyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl; provided that one of R1 and R2 = H and the other is other than H, except that if one of R1 and R2 = aryl then the other = H or 1-12C alkyl; R3, R4H, 1-12C alkyl, cycloalkyl, cycloalkylmethyl, aryl or arylalkyl; provided that at least one of R3 and R4 = H; or one of R1/R2 plus one of R3/R4W', the other of R1/R2 and the other of R3/R4 being H or 1-12C alkyl; W' : (CH2)n, CH=CHCH2, CH2CH=CH, CH=CHCH2CH2, CH2CH=CHCH2, CH2CH2CH=CH, O(CH2)m, CH2-oC6H4-CH2, -oC6H4-CH2, X-oC6H4- or -oC6H4-CH2CH2 (all with the left- and right-hand terminals bonded at the R1/R2 and R3/R4 positions respectively); or cyclopent-1-ene-3,5-diyl or cyclohexane-1,3-diyl: n : 3-6; m : 2-5; X : CH2, O or S; R51-12C alkyl, cycloalkyl, cycloalkylmethyl, aryl, arylalkyl, heterocyclyl, heterocyclylalkyl or C(O)R11; R6H, 1-8C alkyl, CN, halo, NO2, NH2, NHR12, NR13R14, OR15, S(O)pR16, C(O)R17 or -N=N-aryl; R7H, 1-8C alkyl, CN, halo, NO2, NH2, NHR12, NR13R14, OR15, S(O)pR19, C(O)R17 or -N=N-aryl; R8H, 1-8C alkyl or aryl; or R7 + R8C(R21)=C(R22)-C(R23)=C(R24); p : 0-2; R9, R10, R15, R16, R18, R19H, 1-8C alkyl, cycloalkyl, cycloalkylmethyl, aryl or arylalkyl; R11H, 1-8C alkyl, cycloalkyl, cycloalkylmethyl, aryl or OR25; R12alkyl or arylmethyl; R13, R14alkyl; or R13 + R14(CH2)h; h : 4 or 5; R17as R9; or NH2, NHR12, NR13R14 or OR26; R20as R9; or OR27; R21 - R24H, halo or OR28; R25 - R28H or alkyl, provided that R25 is not H if R1 = aryl and R2 = alkyl; unless specified otherwise alkyl groups have 1-6C and cycloalkyl groups 3-8C. Independent claims are included for: (i) the preparation of (I) - (III); (ii) (I) - (III) (including salts, solvates, stereoisomers etc.) as new compounds, with the exception of: 4,5,6,7-tetrahydro-2-methyl-5,7 -diphenyl-pyrazolo (1,5-a) pyrimidine; 4,5,6,7-tetrahydro-2,5-dimethy l-7-phenyl-pyrazolo (1,5-a) pyrimidine; 4,5,6,7-tetrahydro-5,7-methyl -3-phenyl-pyrazolo (1,5-a) pyrimidine; 4,5,6,7-tetrahydro-2,5,7-trime thyl-pyrazolo (1,5-a) pyrimidine; 4,5,6,7-tetrahydro-5,7-dimethyl-2-p henyl-pyrazolo (1,5-a) pyrimidine; 4,5,6,7-tetrahydro-2-methyl-5,7-di -n-propyl-pyrazolo (1,5-a) pyrimidine-3-carbonitrile; 4,5,6,7-tetrahydro-5-methyl-7-(3-(trifluoromethyl)-phenyl)-pyrazolo (1,5-a) pyrimidine-3-carbonitrile; 7-(3- or 4-chlorophenyl)-4,5,6,7-t etrahydro-5-methyl-pyrazolo (1,5-a) pyrimidine-3-carbonitrile; 3,4-dihydro-2-(4-nitrophenyl)-4-phenyl-2H-pyrimido (2,1-b) benzothiazole; and 3,4-dihydro-4-(4-methylphenyl)-2-(4-nitrophenyl)-2 H-pyrimido (2,1-b) benzothiazole; and (iii) combinatorial libraries containing the new compounds as in (ii). - ACTIVITY : Analgesic; anticonvulsant; neuroleptic; neuroprotective; nootropic; antiparkinsonian; cerebroprotective; vasotropic; anti-HIV; auditory; respiratory; cytostatic; antiarrhythmic; immunoregulator; nephrotropic; antiinflammatory; hypnotic; thrombolytic; anticoagulant; uropathic; antidiabetic; antipsoriatic; ophthalmological. - MECHANISM OF ACTION : Nucleoside transport protein ligand; adenosine kinase ligand; adenosine deaminase ligand; A1, A2 and/or A3 receptor ligand. In particular the compounds bind to the MK801 binding site of the NMDA receptor. 7-(3,4-Dimethoxyphenyl)-2-methylsulfanyl-5-phenethyl-tetrah ydro-pyrazolo (1,5-a) pyrimidine-3-carbonitrile (Ia) had Ki 0.3 MicroM in a nucleoside transport protein inhibition assay. |
