Pyrazoles, fused

In 1959 Clinton and coworkers reported the first synthesis of some pyrazole fused androstane derivatives and described their biological activity (B-76MI40404). Stanazolol (695) or 17-methyl-2iT-5o -androst-2-eno[3,2-c]pyrazol-17/3-ol was 10 times as active as 17a -methyltestosterone in improving nitrogen retention in rats (B-80MI40406), and its myotrophic activity was only twice that of 17a-methyltestosterone. It is used as an anabolic steroid with no lasting adverse side effects. 

In the pharmaceutical literature some pyrazoles fused to the prostaglandin structure are cited. Thus, 9,ll-azo-PGE2 (701), a stable endoperoxide analogue that is eight times as potent as PGG2, is a compound that specifically blocks TXA2 synthetase (79MI40401). 

Pyrazole Fused to Another Five-Membered Heterocycle. 283... 

Triazole-fused pyridopyrimidines can be prepared by reaction of aldehydes with the substituted pyridopyrimidine 309 (Equation 106). The pyrazole-fused derivative 311 can be prepared by the reaction of the sulfonimine 310 with dimethyl acetylenedicarboxylate (DMAD) (Equation 107) <1998H(47)871>. 

Extension of the 1,3-DC approach to the synthesis of novel pyrazoline-fused chlorin 78 by the reaction of P-nitro-meso-tetraphenylporphyrin le with diazomethane has also been explored by Cavaleiro and co-workers (Scheme 27) <02S 1155>. The resulting chlorin 78 could be further converted into the pyrazole-fused porphyrin 79 by treatment with DBU or into the methanochlorin 80 by refluxing in toluene. 

Pyrazoles Fused to Five-Membered Heterocycles with One Heteroatom. 269... 

Intramolecular cycloaddition of nitrile ylides to olefinic dipolarophiles linked to the dipole by a three-atom chain leads to pyrazoles fused to five-membered rings. Work on stereoselectivity in such reactions has been carried out using the reactant 266 in which the alkene moiety is linked to the C-terminus via a tether that incorporates an enantiomerically pure (R) stereogenic group (165). Both diastereo-isomers 267 and 268 were isolated and it was found that the reaction showed moderate stereoselectivity favoring 267. 

Crystallographic studies show that pyrazole-fused derivative 136 forms staircase-like 7t-stacked rods <2003TL9161>. AMI calculations have been reported for the pentacyclic system 137 <1996H(43)1991>. 

The molecule contains a sulfonamide and a benzene ring as well as the part that interests us most—a bicydic aromatic heterocyclic system of a pyrazole fused to a pyrimidine. We shall discuss in detail how Pfizer made this part of the molecule and just sketch in the rest. The sulfonamide can be made from the sulfonic acid that can be added to the benzene ring by electrophilic aromatic sulfonation (Chapter 22). 

Terzidis MA, Tsoleridis CA et al (2008) Synthesis of chromeno[2,3-b]carbazole and chro-meno[3,2-f]indazole derivatives. A new class of indole- and pyrazole-fused polycyclic compounds using o-quinodimethane chemistry. A reactivity and regioselectivity computational study. ARKIVOC 132-157... 

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