Nitrosoprodenafil

Nitrosoprodenafil

Systematic (IUPAC) name
2-[(5-[5-(3,5-dimethylpiperazine-1-sulfonyl)-2-ethoxyphenyl]-1-methyl-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-7-yl)oxy]-N-methyl-N-nitroso-1,3-thiazol-5-amine
Clinical data
Legal status
Legal status	US: OTC
Identifiers
CAS Number	1266755-08-1
ATC code	none
ChemSpider	32701496
UNII	X8TO9P16G7
Chemical data
Formula	C28H38N8O5S2
Molar mass	630.780 g/mol
SMILES CCCc1c2c(c(nc(n2)c3cc(ccc3OCC)S(=O)(=O)N4C[C@H](N[C@H](C4)C)C)Oc5ncc(s5)N(C)N=O)n(n1)C
InChI InChI=1S/C27H35N9O5S2/c1-7-9-20-23-24(35(6)32-20)26(41-27-28-13-22(42-27)34(5)33-37)31-25(30-23)19-12-18(10-11-21(19)40-8-2)43(38,39)36-14-16(3)29-17(4)15-36/h10-13,16-17,29H,7-9,14-15H2,1-6H3/t16-,17+ Key:DTAKXJYYAUWRND-CALCHBBNSA-N

Nitrosoprodenafil is a synthetic designer drug found in "herbal" aphrodisiac products, which is a novel nitrosated analogue of sildenafil (Viagra). It has an innovative structure which acts as a prodrug, breaking down in the body to release both the PDE₅ inhibitor aildenafil as well as free nitric oxide, which have powerfully synergistic effects. This dual mechanism of action has never been exploited by conventional pharmaceutical companies because of the risks involved; usually combining PDE₅ inhibitors with nitric oxide releasers like amyl nitrite is contraindicated as it can cause a precipitous drop in blood pressure that can potentially result in death. Nitrosamines are also generally avoided in drug development as they can often be hepatotoxic, so while the combined mechanisms of action are likely to be effective, this drug also has severe risks of toxicity.^[1]

Shortly after Venhuis et al. published the suggested structure for nitrosoprodenafil it was contested by Demizu et al. who suggested the structure was an azathioprine / aildenafil hybrid.^[2] This newly suggested structure was dubbed 'mutaprodenafil' because of the structural similarity with the mutagenic azathioprine.

The final confirmation of the azathioprine / aildenafil hybrid was provided by Sakamoto et al. who prepared crystals for X-ray analysis.^[3] Although Sakamoto et al. support the name 'mutaprodenafil' they prefer to use 'nitroprodenafil' instead.

Proposed structures

See also

• Acetildenafil
• Sulfoaildenafil
• Naproxcinod
• Designer PDE5 inhibitors

References

1. Venhuis, B. J.; Zomer, G.; Hamzink, M.; Meiring, H. D.; Aubin, Y.; de Kaste, D. (2011). "The identification of a nitrosated prodrug of the PDE-5 inhibitor aildenafil in a dietary supplement: a Viagra with a pop". Journal of Pharmaceutical and Biomedical Analysis 54 (4): 735–741. doi:10.1016/j.jpba.2010.11.020. PMID 21145686.
2. Demizu, Y.; Wakana, D.; Kamakure, H.; Kurehara, M.; Okuda, M.; Goda, Y. (2011). "Identification of Mutaprodenafil in a Dietary Supplement and its Subsequent Synthesis". Chem. Pharm. Bull. 59: 1314–1316. doi:10.1248/cpb.59.1314.
3. Sakamoto, M.; Moriyasu, T.; Minowa, K.; Kishimoto, K.; Kadoi, H.; Hamano, T.; Fukaya, H. (2012). "Structure Elucidation of a Novel Analog of Sildenafil Detected as an Adulterant in a Dietary Supplement Using LC-UV and LC/MS". Journal of AOAC International 95 (4): 1048–1052. doi:10.5740/jaoacint.11-235.