Compound 118 (Fig. 7) was a novel meroterpenoid possessing respective 4/5/6/6/6 polycyclic ring systems [46].
Structure activity relationships of two different regions of the chemotype (polycyclic ring and substituents on quaternary carbon) are discussed.
Sulfonamides/carboxylates incorporating polycyclic ring systems such as benzothiopyranopyrimidine, pyridothiopyranopyrimidine or dihydrobenzothiopyrano[4,3-c]pyrazole may be considered as interesting candidates for exploring the design of isoform-selective CAIs with various pharmacologic applications.
Polycyclic ring structures are useful as starting scaffolds in medicinal chemistry programs to develop multi-functional drugs, and may also be useful moieties added to existing structures to improve the pharmacokinetic properties of drugs currently used in the clinic or under development.
As shown in Figure 2, the Black sample was dominated by Actinomycetales such as Brevibacterium and Corynebacterium that volatilize sulfur via an organic intermediate and can also break down complex heterocyclic and polycyclic ring structures[ 17, 18].
Products containing the 1,3-dicarbonyl component within various polycyclic ring systems were also prepared (4 p– 4 r and 4 v), although the enantioselectivities of 4 p and 4 q were more modest.
This, in addition to the orientation of the polycyclic ring system in RdmE, has provided anchoring positions for modelling the HbpA product 23DHBP into the substrate-binding pocket of HbpA.
The lowest RMSEtest value of 0.53 pGI50 units was obtained for cluster 24, which contains 485 compounds with polycyclic ring systems, generally with no more than three fused rings, as well as ring assemblies linked by sulphide, sulfinyl, secondary amine, carbonyl and alkyl groups (Supplementary Table S13).
In the HbpA model product complex, the phenyl ring of the product is accommodated in a hydrophobic pocket formed by the side chains of Pro320, Met321, Trp225 and Met223, similar to the binding mode of the polycyclic ring system of aklavinone in RdmE, although the phenyl ring is rotated 90° relative to the phenol.
Though all contained polycyclic heteroaromatic rings, these varied from two –to four-ringed structures.
