–1
Androst-4-en-3,17-dione disemicarbazone (7), mp 292–294°C (EtOH). IR spectrum (ꢄ, cm ): 3400 (NH ), 1710
2
(C=O), 1635 (N=C). PMR spectrum (ꢂ, ppm): 0.83 (3H, s, 18-CH ), 1.03 (3H, s, 19-CH ), 5.74 (1H, s, H-4), 6.07 (2H, br.s)
3
3
and 6.18 (2H, br.s, NH ), 9.03 (1H, s, NH on C-3), 8.68 (1H, s, NH on C-17).
2
5ꢁ-Pregn-2-en-20-one Isonicotinoylhydrazone (8). A mixture of ketosteroid 2 (0.2 g, 0.66 mmol), isoniazide
(0.1 g, 0.81 mmol), and HOAc (0.5 mL) in EtOH (10 mL) was refluxed for 5 h. The precipitate that formed on cooling was
–1
filtered off and washed with H O to afford the hydrazone (0.25 g, 92%), mp 154–156°C (EtOH). IR spectrum (ꢄ, cm ): 3320
2
(NH), 1650 (NHC=O), 1625 (C=N), 1530 (Py ring). PMR spectrum (ꢂ, ppm): 0.77 (3H, s, 18-CH ), 0.79 (3H, s, 19-CH ),
3
3
1.74 (3H, s, 21-CH ), 5.50-5.63 (2H, m, CH=CH), 7.69 (2H, br.s) and 8.72 (2H, br.s, Py ring), 8.91 (1H, s, NH).
3
Compounds 9 and 10 were prepared analogously.
5ꢁ-Androstan-3,17-dione diisonicotinoylhydrazone (9), mp 276–278°C (MeOH) (lit. [12] mp 275–277°C).
–1
IR spectrum (ꢄ, cm ): 3380 (NH), 1700 (C=O), 1635 (N=C), 1530 (Py ring). PMR spectrum (ꢂ, ppm): 0.91 (3H, s, 18-CH ),
3
1.17 (3H, s, 19-CH ), 10.85 (1H, s, NH on C-3), 10.44 (1H, s, NH on C-17), 7.59 (2H, m) and 7.61 (2H, m, H-2,6 Py ring),
3
8.64 (2H, m) and 8.70 (2H, m, H-3,5 Py ring).
Androst-4-en-3,17-dione diisonicotinoylhydrazone (10), mp 292–294°C (MeOH) (lit. [12] mp 293–296°C).
–1
IR spectrum (ꢄ, cm ): 3370 (NH), 1710 (C=O), 1630 (C=N), 1525 (Py ring). PMR spectrum (ꢂ, ppm): 0.94 (3H, s, 18-CH ),
3
1.1 (3H, s, 19-CH ), 5.91 (1H, s, H-4), 10.96 (1H, s, NH on C-3), 10.72 (1H, s, NH on C-17), 7.54 (2H, m) and 7.74 (2H, m,
3
H-2,6 Py ring), 8.64 (2H, m) and 8.71 (2H, m, H-3,5 Py ring).
Compounds 5–10 and adamantane-containing 5ꢁ-steroids 11–13 were tested using the TAACF program of the National
Institute of Allergy and Infectious Diseases of the National Institutes of Health. Preliminary activity screening of the compounds
at a concentration of 6.25 ꢃg/mL against a M. tuberculosis strain (ATCC 27294) in BACTEC 12B medium was performed
using the MABA.
Compounds exhibiting inhibiting activity <90% at this concentration were excluded from further testing. Compounds
exhibiting anti-TB activity were studied in the second stage at lower concentrations against the same M. tuberculosis strain.
ACKNOWLEDGMENT
We thank C. Kwong, Coordinator of the TAACF-USA program, for leading the biological tests. The work was
supported financially by the Sh. Rustaveli Georgian National Foundation (Grant No. GNSF/ST08/4-406).
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