Pyrazolate-based compounds

Merck has recently utilised a furo[2,3-b]pyridine core (554) as a bioisosteric replacement for the pyrazole scaffold of rimonabant (382) [328]. The same basic pharmacophore, that of two halo-substituted aryl groups and a third hydrophobic motif proximal to a hydrogen-bond acceptor, can be witnessed in the benzodioxole-based compounds, such as (555), disclosed by Roche [329]. 

Tetranuclear Ni11 complexes (889), (890a), and (890b) with unusual /i3-l,l,3 and /r4-1,1,3,3 azide binding modes have been obtained from discrete pyrazolate-based dinuclear building blocks.2141 (890a) and (890b) represent the only known examples of such EE/EO /i4 coordination of azide in molecular compounds. 

Related pyrazole-containing compounds such as 500 and 161 (Figure 33) have shown similar properties in 1 M H2SC>4 using electrochemical methods the choice of these molecules is based on the presence of an electron cloud on the aromatic rings, the presence of 71 electrons of N = N, C = N, C = O, and C = S is expected to affect the corrosion of carbon steel <2003MI1>. 

In contrast to the pyrazole-urea-based compounds, the inhibitor class similar to SB203580 has been described as DFG-in binders [95], where the conformation of the DFG loop is similar to that observed in the crystal structures of apo form of p38 [96, 97]. SB203580 or SKF86002 as DFG-in ligands of p38 do not invoke additional peaks in the pH, 1,5N]-TROSY spectrum of 15N-Phe-p38. The observed NMR data suggests that the reported DFG-in binders leave a putative conformational DFG in/out equilibrium in a time regime,... 

The condensation of pyrazole-based chalcone 55 with hydrazine (in the presence of acetic acid) and with phen-ylhydrazine in PEG 400 resulted in the pyrazoline ring closure (Scheme 32) [56]. Some of the reaction products demonstrated anti-inflammatory and analgesic activities. The type and potency of the observed effects were mainly dependent on the substituents (Ar) with no significant difference between two types of compounds 56 and 57. 

Based on the spectroscopic data (supported by three single-crystal structure determinations) it is shown that the more basic 3,5-dimethylpyrazole-based compound produces many more co-crystals than the corresponding (and less basic) pyrazole ligand, 20/30 (67%) vs 11/30 (37%). The presence of the methyl groups in 2 have increased the magnitude of the negative electrostatic potential on the nitrogen atoms which is also reflected in the basicity of 2. 

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