Chemistry:Pudafensine
Pudafensine (INN; developmental code name IP2015 among others) is a serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI) which is under development for the treatment of erectile dysfunction, neuropathic pain, trigeminal neuralgia, vulvodynia, female sexual dysfunction, pain, and substance-related disorders.[1][2][3][4] It is taken orally.[3] The drug has been found to induce penile erection in male rodents and to increase genital blood flow and paracopulatory behaviors in female rodents.[2][4] A close analogue of pudafensine is the earlier SNDRI NS18283.[5] Pudafensine is under development by Initiator Pharma.[1] As of July 2025, it is in phase 2 clinical trials for erectile dysfunction, phase 1 trials for neuropathic pain, trigeminal neuralgia, and vulvodynia, and the preclinical research stage of development for female sexual dysfunction, pain, and substance-related disorders.[1]
Chemistry
Synthesis
The chemical synthesis of pudafensine was disclosed:[6] Precursor:[7]
The reaction of endo-Tropacocaine [19145-60-9] (1) with 2,2,2-Trichloroethyl chloroformate (Troc group) [17341-93-4] (2) gave the urethane PC11463908 (3). Reduction with zinc in acetic acid afforded the nortropane, PC11458897 (4). Protection of the secondary amine with Boc anhydride gave PC66624775 (5). Saponification of the ester in potassium hydroxide gave PC11160507 (6). Mitsunobu reaction with 7-hydroxy-3-methoxy-chromen-2-one (Methoxy-Umbelliferon) [68287-05-8] (7) occurred with inversion of stereochemistry from the endo to the exo position, PC89405050 (8). Acid hydrolysis of the Boc protecting group completed the synthesis of pudafensine (9).
See also
- List of investigational sexual dysfunction drugs
- List of investigational analgesics
- List of investigational substance-related disorder drugs
References
- ↑ 1.0 1.1 1.2 "Initiator Pharma". 29 July 2025. https://adisinsight.springer.com/drugs/800066919.
- ↑ 2.0 2.1 "Pudafensine, a Monoamine Reuptake Inhibitor, Promotes Paracopulatory Behaviors and Increases Genitalia Flow in Female Rats". The Journal of Sexual Medicine 22 (Supplement_2). 9 May 2025. doi:10.1093/jsxmed/qdaf077.005. ISSN 1743-6095. https://academic.oup.com/jsm/article/doi/10.1093/jsxmed/qdaf077.005/8127951. Retrieved 26 January 2026.
- ↑ 3.0 3.1 "(191) A Phase II Repeat Single Oral Dose Study of IP2015 or Placebo in Healthy Male Subjects With Erectile Dysfunction". The Journal of Sexual Medicine 22 (Supplement_1). 25 April 2025. doi:10.1093/jsxmed/qdaf068.167. ISSN 1743-6095. https://academic.oup.com/jsm/article/doi/10.1093/jsxmed/qdaf068.167/8119656. Retrieved 26 January 2026.
- ↑ 4.0 4.1 "A novel reuptake inhibitor, IP2015, induces erection by increasing central dopamine and peripheral nitric oxide release". British Journal of Pharmacology 181 (15): 2566–2582. August 2024. doi:10.1111/bph.16362. PMID 38604613.
- ↑ "Antinociceptive activity of the new triple reuptake inhibitor NS18283 in a mouse model of chemotherapy-induced neuropathic pain". European Journal of Pain 19 (3): 322–333. March 2015. doi:10.1002/ejp.550. PMID 25045036.
- ↑ Dan Peters, et al. WO2011092061 (to NTG Nordic Transport Group AS).
- ↑ "Anti-AIDS Agents. 37. Synthesis and Structure−Activity Relationships of (3‘ R ,4‘ R )-(+)- cis -Khellactone Derivatives as Novel Potent Anti-HIV Agents". Journal of Medicinal Chemistry 42 (14): 2662–2672. 1 July 1999. doi:10.1021/jm9900624. https://pubs.acs.org/doi/10.1021/jm9900624.
External links
Template:Sexual dysfunction medications
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