In the case of 1-[2-thiazol-4-yl-(2-aminoethyl)]-4-n-propylpiperazines, elongation of alkyl chain from one to three methylene check details groups results in an increase of potency for 2a pA2 = 6.76 and 2b pA2 = 6.96, this is in opposition to the 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazine derivatives where the 1-[2-thiazol-5-yl-(2-N,N-dimethylaminoethyl)]-4-n-propylpiperazine shows slightly higher potency than its N-methyl-N-propyl analogue (pA2 = 7.78; pA2 = 7.53, respectively). In the 2-methyl-2-phenylalkyl derivatives of 1-[2-thiazol-4-yl-(2-aminoethyl)]-4-n-propylpiperazine (2c–g), there is no significant difference in affinity. Elongation of alkyl chain from one to five methylene groups does not influence

antagonistic activity (pA2 ranging from 6.81 for compound 2d to 6.69 for compound 2g). In the analogues series, there is no significant EPZ015938 mouse difference in affinity among the methyl and ethyl derivatives (pA2 = 7.76 and 7.61 for compound 3a). A further elongation in the alkyl chain length to 3 methylene groups results in an increase

of antagonistic activity, reaching the maximum for 1-[2-thiazol-5-yl-(2-methyl-2-phenylpropylaminoethyl)]-4-n-propylpiperazine (pA2 = 8.27); activity decreases on further lengthening up to 5 methylene groups (pA2 = 7.80 for compound 3b and 7.25 for 1-[2-thiazol-5-yl-(2-phenylpentylmethylaminoethyl)]-4-n-propylpiperazine). Replacement of hydrogen by p-benzoyl substituent at the end of N-methyl Methisazone group leads to the compounds 2h–k (pA2 from 5.65 to 6.23) and their analogues 4a–d (pA2 from 7.45 to 7.76). By comparison of homologous pairs, the 1-[2-thiazol-5-yl-(2-methyl-2-phenylcarbonylaminoethyl)]-4-n-propylpiperazine

amides 4a–d have much higher potency than their analogous 1-[2-thiazol-4-yl-(2-methyl-2-phenylcarbonylaminoethyl)]-4-n-propylpiperazine amides 2h–k. In both series, a slightly higher activity is observed for compounds carrying on electron-withdrawing substituent at para-position in the benzene ring. Summarizing, 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazines display a higher activity than their 1-[2-thiazol-4-yl-(2-aminoethyl)]-4-n-propylpiperazine analogues. We observe that the position 5 of 2-methyl-2-R-aminoethyl-substituents in the thiazole ring is favourable for histamine H3 Selleck Wortmannin receptor antagonist activity, whereas its presence in position 4 leads, almost in each case, to strong decrease of activity. The highest potency for both homologous series is seen in the compound with the 2-methyl-2-phenylpropylaminoethyl substituent (pA2 = 8.27) and with slightly lower potencies for compounds carrying on 2,2-dimethylaminoethyl, 2-methyl-2-(4-chlorophenyl)carbonylaminoethyl and 2-methyl-2-(4-nitrophenyl)-carbonylaminoethyl substituents (pA2 = 7.78; pA2 = 7.73 and pA2 = 7.76, respectively). Experimental protocols General Methods. All melting points (mp) were measured in open capillaries on an electrothermal apparatus and are uncorrected.