Table 1.
Lipophilicity data and putative effect of Rp-cGMPS analogs
| Compound | Analog | log k′g | rLcGMP* | Effect on PKG | Effect on CNGC |
| A | cGMP | 0.770 | 1.0 | + | + |
| B | RP-cGMPS | 0.894 | 1.3 | − | + |
| C | RP-8-Br-cGMPS | 1.285 | 3.3 | − | + |
| CN01 | 8-pCPT-cGMP | 2.520 | 56 | + | + |
| CN02 | RP-8-pCPT-cGMPS | 2.610 | 69 | − | + |
| CN03 | RP-8-Br-PET-cGMPS | 2.831 | 115 | − | − |
| CN04 | RP-8-pCPT-PET-cGMPS | 3.530 | 575 | − | ±† |
| CN05 | RP-8-pHPT-PET-cGMPS | 3.078 | 203 | − | ±† |
| CN06 | RP-8-pIPrPT-PET-cGMPS | 3.815 | 1,109 | − | ±† |
| CN07 | RP-8-Br-(3-Tp)ET-cGMPS | 2.746 | 95 | − | − |
| CN08 | RP-8-oAPT-cGMPS | 1.974 | 16 | − | + |
| CN09 | RP-cGMPS-8-TMAmd-(EO)8-EAmdMT-8-RP-cGMPS | 2.039‡ | 19 | − | + |
| CN10 | PET-RP-cGMPS-8-TMAmd-(EO)8-EAmdMT-8-RP-cGMPS-PET | 3.236‡ | 292 | − | ±† |
“+” indicates a PKG/CNGC activator; “−” indicates inhibitor.
*
Relative lipophilicity of Rp-cGMPS analog compared with cGMP.
†
No distinct assignment as CNGC inhibitor, as large substituents in 8 position tend to activate CNGC and might overrule inhibition induced by PET or PET-like substitution.
‡
Values for dimeric analogs are not directly comparable with values for monomeric analogs.