JNJ-37654032

JNJ-37654032
Clinical data
Other names	JNJ37654032
Drug class	Selective androgen receptor modulator
Identifiers
	IUPAC name 2-(5,6-dichloro-1H-benzimidazol-2-yl)-1,1,1-trifluorobut-3-en-2-ol;
CAS Number	944919-15-7;
PubChem CID	23729483;
ChemSpider	23307734;
UNII	K3976EA8Z4;
ChEMBL	ChEMBL246007;
Chemical and physical data
Formula	C11H7Cl2F3N2O
Molar mass	311.09 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C=CC(C1=NC2=CC(=C(C=C2N1)Cl)Cl)(C(F)(F)F)O;
	InChI InChI=1S/C11H7Cl2F3N2O/c1-2-10(19,11(14,15)16)9-17-7-3-5(12)6(13)4-8(7)18-9/h2-4,19H,1H2,(H,17,18); Key:HEDZSNUSVHSSQI-UHFFFAOYSA-N;

JNJ-37654032 is a selective androgen receptor modulator (SARM) which was developed by Johnson & Johnson for the potential treatment of muscular atrophy but was never marketed.^[1]^[2]^[3]^[4]

The drug is a nonsteroidal androgen receptor (AR) modulator with mixed agonistic (androgenic) and antagonistic (antiandrogenic) effects.^[4] In animals, it has shown full agonist-like effects in muscle, agonistic suppressive effects on follicle-stimulating hormone (FSH) secretion, and antagonistic or partially agonistic effects in the prostate.^[5]^[6]^[3]^[4] It was the lead compound of a novel benzimidazole series of SARMs described as being reminiscent of but distinct from the arylpropionamides (e.g., enobosarm).^[5]^[4]

JNJ-37654032 did not advance past the preclinical research and was never tested in humans.^[1]^[7] It was first described in the scientific literature by 2008.^[4]

References

^ ^a ^b "Delving into the Latest Updates on JNJ-37654032 with Synapse". Synapse. 13 October 2024. Retrieved 22 October 2024.
^ Xie Y, Tian Y, Zhang Y, Zhang Z, Chen R, Li M, et al. (February 2022). "Overview of the development of selective androgen receptor modulators (SARMs) as pharmacological treatment for osteoporosis (1998-2021)". European Journal of Medicinal Chemistry. 230: 114119. doi:10.1016/j.ejmech.2022.114119. PMID 35063736.
^ ^a ^b Clarke BL, Khosla S (2010). "Modulators of androgen and estrogen receptor activity". Critical Reviews in Eukaryotic Gene Expression. 20 (4): 275–294. doi:10.1615/critreveukargeneexpr.v20.i4.10. PMID 21395502.
^ ^a ^b ^c ^d ^e Allan G, Sbriscia T, Linton O, Lai MT, Haynes-Johnson D, Bhattacharjee S, et al. (June 2008). "A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats". The Journal of Steroid Biochemistry and Molecular Biology. 110 (3–5): 207–213. doi:10.1016/j.jsbmb.2007.10.012. PMID 18502117.
^ ^a ^b Mohler ML, Bohl CE, Jones A, Coss CC, Narayanan R, He Y, et al. (June 2009). "Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit". Journal of Medicinal Chemistry. 52 (12): 3597–3617. doi:10.1021/jm900280m. PMID 19432422. A recently reported benzimidazole A-ring chemotype contained a tertiary alcohol (presumably to interact with N705) reminiscent of the propionamide scaffold but lacks a B-ring system. The lead molecule JNJ-3765403225 (24) (Table 2) was reportedly a full myoanaobolic agonist that restored LBM in castrated rats by 20% and suppressed FSH.25 In intact rats, androgenic antagonism was observed as decreased testes size and 47% reduction in VP weight (i.e., VP antagonism) while maintaining 100% LA.
^ Tabbal M, Fuleihan EH (2010). "Future Therapies". Osteoporosis in Men. Elsevier. pp. 713–732. doi:10.1016/b978-0-12-374602-3.00057-2. ISBN 978-0-12-374602-3. Similarly, JNJ-37654032 was shown to selectively stimulate growth of the levator ani muscle, without stimulating prostate growth, while reducing FSH levels, in an orchidectomized rat model. Conversely, in the intact rats, the compound reduced prostate growth, size of the testes, without having any inhibitory effect on muscle [69].
^ Fonseca GW, Dworatzek E, Ebner N, Von Haehling S (August 2020). "Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials". Expert Opinion on Investigational Drugs. 29 (8): 881–891. doi:10.1080/13543784.2020.1777275. PMID 32476495.

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[Synapse-1] "Delving into the Latest Updates on JNJ-37654032 with Synapse". Synapse. 13 October 2024. Retrieved 22 October 2024.

[XieTianZhang2022-2] Xie Y, Tian Y, Zhang Y, Zhang Z, Chen R, Li M, et al. (February 2022). "Overview of the development of selective androgen receptor modulators (SARMs) as pharmacological treatment for osteoporosis (1998-2021)". European Journal of Medicinal Chemistry. 230: 114119. doi:10.1016/j.ejmech.2022.114119. PMID 35063736.

[ClarkeKhosla2010-3] Clarke BL, Khosla S (2010). "Modulators of androgen and estrogen receptor activity". Critical Reviews in Eukaryotic Gene Expression. 20 (4): 275–294. doi:10.1615/critreveukargeneexpr.v20.i4.10. PMID 21395502.

[AllanSbrisciaLinton2008-4] Allan G, Sbriscia T, Linton O, Lai MT, Haynes-Johnson D, Bhattacharjee S, et al. (June 2008). "A selective androgen receptor modulator with minimal prostate hypertrophic activity restores lean body mass in aged orchidectomized male rats". The Journal of Steroid Biochemistry and Molecular Biology. 110 (3–5): 207–213. doi:10.1016/j.jsbmb.2007.10.012. PMID 18502117.

[MohlerBohlJones2009-5] Mohler ML, Bohl CE, Jones A, Coss CC, Narayanan R, He Y, et al. (June 2009). "Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit". Journal of Medicinal Chemistry. 52 (12): 3597–3617. doi:10.1021/jm900280m. PMID 19432422. A recently reported benzimidazole A-ring chemotype contained a tertiary alcohol (presumably to interact with N705) reminiscent of the propionamide scaffold but lacks a B-ring system. The lead molecule JNJ-3765403225 (24) (Table 2) was reportedly a full myoanaobolic agonist that restored LBM in castrated rats by 20% and suppressed FSH.25 In intact rats, androgenic antagonism was observed as decreased testes size and 47% reduction in VP weight (i.e., VP antagonism) while maintaining 100% LA.

[TabbalFuleihan2010-6] Tabbal M, Fuleihan EH (2010). "Future Therapies". Osteoporosis in Men. Elsevier. pp. 713–732. doi:10.1016/b978-0-12-374602-3.00057-2. ISBN 978-0-12-374602-3. Similarly, JNJ-37654032 was shown to selectively stimulate growth of the levator ani muscle, without stimulating prostate growth, while reducing FSH levels, in an orchidectomized rat model. Conversely, in the intact rats, the compound reduced prostate growth, size of the testes, without having any inhibitory effect on muscle [69].

[FonsecaDworatzekEbner2020-7] Fonseca GW, Dworatzek E, Ebner N, Von Haehling S (August 2020). "Selective androgen receptor modulators (SARMs) as pharmacological treatment for muscle wasting in ongoing clinical trials". Expert Opinion on Investigational Drugs. 29 (8): 881–891. doi:10.1080/13543784.2020.1777275. PMID 32476495.

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