Synthesis and Bioactivity of Nandrolone phenylpropionate

General description

Nandrolone phenylpropionate is a commonly used hormone that promotes protein synthesis and metabolism, alias Nandrolone phenylpropionate, Positive Male Ketone, Nortestosterone phenylpropionate, Dole Baolong, Dole Baoling.

Synthetic routes

Fig. 2 The synthetic method 1 of Nandrolone phenylpropionate.

Add anhydrous MeCN (0.5 mL) to a mixture of 3-phenylpropanoic acid (30.0 mg, 0.2 mmol, 1.0 equiv), aryneprecursor (119.2 mg, 0.4 mmol, 2.0 equiv), nandrolone (82.3 mg, 0.3 mmol, 1.5 equiv), CsF (182.3 mg, 1.2 mmol, 6.0 equiv), K₂CO₃ (82.9 mg, 0.6 mmol, 3.0 equiv), and 18-crown-6 (158.6 mg, 0.6 mmol, 3.0 equiv). Warm the mixture to 70 ℃ in an oil bath and stir at this temperature for8 hours. Remove all the volatiles directly on rotary evaporator. Purify by flash column chromatography with pet ether:EtOAc = 20:1. ¹H NMR (400 MHz, CDCl₃) δ 7.31-7.26(m,2H), 7.23-7.17(m,3H), 5.83 (s, lH), 4.65-4.58(m, lH), 2.95(t, J= 8.0 Hz,2H), 2.64(t, J= 8.0 Hz,2H), 2.51-2.36(m, 2H), 2.31-2.04(m, 5H), 1.86-1.79(m, 2H), 1.72-1.61 (m, 2H), 1.57-1.00(m, 8H),0.90-0.81(m, 1H), 0.79 (s, 3H)ppm [1].

Pharmacokinetics and pharmacodynamics

Minto et al. studied healthy men who underwent blood sampling for plasma nandrolone, testosterone and inhibin measurements before and for 32 days after a single i.m. injection of 100 mg of nandrolone ester in arachis oil. Twenty-three men were randomized into groups receiving nandrolone phenylpropionate (group 1, n = 7) or nandrolone decanoate (group 2, n = 6) injected into the gluteal muscle in 4 ml of arachis oil vehicle or nandrolone decanoate in 1 mi of arachis oil vehicle injected into either the gluteal (group 3, n = 5) or deltoid (group 4, n = 5) muscles. Plasma nandrolone, testosterone and inhibin concentrations were analyzed by a mixed-effects indirect response model. Plasma nandrolone concentrations were influenced (P <.001) by different esters and injection sites, with higher and earlier peaks with the phenylpropionate ester, compared with the decanoate ester. After nandrolone decanoate injection, the highest bioavailability and peak nandrolone levels were observed with the 1-ml gluteal injection. Plasma testosterone concentrations were also influenced (P <.001) by the ester and injection site, with the most rapid, but briefest, suppression being due to the phenylpropionate ester, whereas the most sustained suppression was achieved with the 1-ml gluteal injection. Plasma inhibin concentrations were also significantly influenced by injection volume and site, with the lowest nadir occurring after the nandrolone decanoate 1-ml gluteal injection. Thus, the bioavailability and physiological effects of a nandrolone ester in an oil vehicle are greatest when the ester is injected in a small (1 mi vs. 4 mi) volume and into the gluteal vs. deltoid muscle. We conclude that the side-chain ester and the injection site and volume influence the pharmacokinetics and pharmacodynamics of nandrolone esters in an oil vehicle in men [2].

Detection method

Mukherjee et al. describes development and subsequent validation of a reversed phase high performance liquid chromatographic (RP-HPLC) method for the estimation of nandrolone phenylpropionate, an anabolic steroid, in bulk drug, in conventional parenteral dosage formulation and in prepared nanoparticle dosage form. The chromatographic system consisted of a Luna Phenomenex, CN (250 mm x 4.6 mm, 5 mu m) column, an isocratic mobile phase comprising 10 mM phosphate buffer and acetonitrile (50:50, v/v) and UV detection at 240 nm. Nandrolone phenylpropionate was eluted about 6.3 min with no interfering peaks of excipients used for the preparation of dosage forms. The method was linear over the range from 0.050 to 25 mu g/mL in raw drug (r(2) = 0.9994). The intra-day and inter-day precision values were in the range of 0.219-0.609% and 0.441-0.875%, respectively. Limits of detection and quantitation were 0.010 mu g/mL and 0.050 mu g/mL, respectively. The results were validated according to International Conference on Harmonization (ICH) guidelines in parenteral and prepared nanoparticle formulation. The validated HPLC method is simple, sensitive, precise, accurate and reproducible [3].

Bioactivity

Effects on the healing of ischemic colon anastomosis in rats

PURPOSE: Recombinant human growth hormone and nandrolone phenylpropionate are two different anabolic agents. This study was designed to investigate the effects of these anabolic agents on the heating of ischemic colon anastomosis in rats. METHODS: Seventy adult male Wistar rats were divided into five groups (n = 14). Group I was the sham laparotomy group. In the other groups, surgical procedures consisting of transsection and anastomosis were made at a distance 3 cm from the peritoneal reflection. Group II was the nonischemic control group. Ischemic colon model was produced in the remaining groups. Group III was the untreated control group. Groups IV and V received recombinant human growth hormone and nandrolone phenylpropionate, respectively. Bursting pressure and hydroxyproline levels were measured on the third and seventh postoperative days to evaluate anastomotic heating. RESULTS: Recombinant human growth hormone increased both collagen deposition and bursting pressure significantly at postoperative Days 3 and 7 compared with the sham and untreated control groups (P < 0.005). When compared with the untreated control, nandrolone phenylpropionate significantly increased collagen deposition at postoperative Days 3 and 7 (P < 0.005) and bursting pressure only at postoperative Day 3 (P < 0.005). CONCLUSIONS: Recombinant human growth hormone has more favorable therapeutic effects on the healing of ischemic colonic anastomoses than nandrolone phenylpropionate. Recombinant human growth hormone also improves healing of nonischemic colonic anastomosis [4].

Effect on expression of hepatic albumin-mRNA and androgen receptor in burned rats

OBJECTIVE: To study the mechanism of nandrolone phenylpropionate (NP) on hepatic albumin mRNA and androgen receptor (AR) in burned rats.  METHODS: Thirty-two Wistar rats with a deep second-degree cutaneous burn of 20% total body surface area were randomly divided into two groups: NP group (experimental group, 5 mg/kg NP) and normal saline as control group every other day. The expression copy quantity of albumin-mRNA and mean integrated absorbency(mIA) of AR in liver tissue were measured by quantitative fluorescent RT-PCR and immunohistochemistry respectively on the 4th, 7th, 14th and 21st days of post-burned.  RESULTS: The expression levels of albumin-mRNA and AR in liver tissue in NP group were much higher than those in control group. The albumin-mRNA and AR expression increased significantly (P < 0.05) after 7 and 14 days, while the expression had no significant difference between NP group and control group on the 4th day. A positive correlation occurred between the expression level of albumin-mRNA and the quantity of AR in liver tissue(r = 0.936, P < 0.05).  CONCLUSION: Nandrolone phenylpropionate up-regulated respectively the expression of albumin-mRNA and the density of AR in liver tissue [5].

Effects on craniofacial growth in rats

Primary testosterone and its derivatives are anabolic steroids used in the treatment of osteoporosis and Turner syndrome. They also enhance fast-twitch muscle weight in female rats. The present study examines the effect of an anabolic steroid on craniofacial growth and development in rats. Five-week-old female Sprague-Dawley rats (125) were divided into experimental and control groups. The experimental group was injected subcutaneously with 1 mg nandrolone phenylpropionate in the interscapular region on alternate days, whereas those in the control group were injected with a vehicle, arachis oil. Rats were sacrificed at 60 and 120 days of age. Cephalometric analysis of soft X-ray cephalograms showed that chronic administration of the anabolic steroid, nandrolone phenylpropionate, resulted in: (1) about a 20% increase in body weight, (2) an increase in total skull length, (3) elongation of the maxillary and mandibular incisors, (4) an increase in the depth of the antegonial notch, and (5) downward-forward growth of the viscerocranium against the neurocranium. These results suggest that nandrolone phenylpropionate may accelerate craniofacial growth and/or induce high functional activity of the masticatory muscles in female rats [6].

References

[1] Zhao J, Shi J, Li Y. Benzyne-Mediated Esterification Reaction[J]. Organic Letters, 2021, 23(18): 7274-7278.

[2] Minto C F, Howe C, Wishart S, et al. Pharmacokinetics and pharmacodynamics of nandrolone esters in oil vehicle: effects of ester, injection site and injection volume[J]. Journal of pharmacology and experimental therapeutics, 1997, 281(1): 93-102.

[3] Mukherjee J, Das A, Chakrabarty U S, et al. Development and validation of RP HPLC method to determine nandrolone phenylpropionate in different pharmaceutical formulations[J]. Acta Pol. Pharm, 2011, 68: 155.

[4] Yarimkaya A, Apaydin B, Unal E, et al. Effects of recombinant human growth hormone and nandrolone phenylpropionate on the healing of ischemie colon anastomosis in rats[J]. Diseases of the colon & rectum, 2003, 46(12): 1690-1697.

[5] Cen Y, Li K, Liu X X. Effect of nandrolone phenylpropionate on expression of hepatic albumin-mRNA and androgen receptor in burned rats[J]. Zhongguo xiu fu Chong Jian wai ke za zhi= Zhongguo Xiufu Chongjian Waike Zazhi= Chinese Journal of Reparative and Reconstructive Surgery, 2003, 17(6): 439-441.

[6] Noda K, Chang H P, Takahashi I, et al. Effects of the anabolic steroid nandrolone phenylpropionate on craniofacial growth in rats[J]. Journal of morphology, 1994, 220(1): 25-33.

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