Synthesis and biological activity of a new progestogen, 16-methylene- 17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate

Zoltán Tuba, C. Wayne Bardin, Anna Dancsi, Erzsébet Francsics-Czinege, Csaba Molnár, János Csörgei, G. Falkay, Samuel S. Koide, Narender Kumar, Kalyan Sundaram, Vilma Dukát-Abrók, Gábor Balogh

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The progestational activity of second- and third-generation progestins in oral contraceptives were markedly increased by addition of an 18-methyl group. A new progestin, the 18-methyl analog of Nestorone, 16-methylene-17α- hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate (10), was synthesized. The relative binding affinity and biologic activity of 10 was compared with Nestorone, levonorgestrel, and progesterone using a binding assay for rat progesterone receptors, the Clauberg assay in the rabbit, and by assessing pregnancy maintenance in the rat. These studies, as summarized in Table 4, show that 10 is three to ten times more potent than Nestorone. The addition of the 18-methyl group to Nestorone markedly increased its potency as noted above, but is unlikely to change its rate of delivery from sustained release systems. 10 should be ideally suited for administration by implants or small skin patches. (C) 2000 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)266-274
Number of pages9
JournalSteroids
Volume65
Issue number5
DOIs
Publication statusPublished - May 2000

Fingerprint

Progestins
Bioactivity
Rats
Assays
Pregnancy Maintenance
Levonorgestrel
Progesterone Receptors
Oral Contraceptives
Progesterone
Skin
Rabbits
16-methylene-17-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate
ST 1435

Keywords

  • 16-methylene-17α-hydroxy-18-methyl-19-norpregn-4-ene-3
  • 20- dione acetate
  • Clauberg assay
  • Nestorone
  • Progestin
  • Synthesis

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Tuba, Z., Bardin, C. W., Dancsi, A., Francsics-Czinege, E., Molnár, C., Csörgei, J., ... Balogh, G. (2000). Synthesis and biological activity of a new progestogen, 16-methylene- 17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate. Steroids, 65(5), 266-274. https://doi.org/10.1016/S0039-128X(99)00109-9

Synthesis and biological activity of a new progestogen, 16-methylene- 17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate. / Tuba, Zoltán; Bardin, C. Wayne; Dancsi, Anna; Francsics-Czinege, Erzsébet; Molnár, Csaba; Csörgei, János; Falkay, G.; Koide, Samuel S.; Kumar, Narender; Sundaram, Kalyan; Dukát-Abrók, Vilma; Balogh, Gábor.

In: Steroids, Vol. 65, No. 5, 05.2000, p. 266-274.

Research output: Contribution to journalArticle

Tuba, Z, Bardin, CW, Dancsi, A, Francsics-Czinege, E, Molnár, C, Csörgei, J, Falkay, G, Koide, SS, Kumar, N, Sundaram, K, Dukát-Abrók, V & Balogh, G 2000, 'Synthesis and biological activity of a new progestogen, 16-methylene- 17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate', Steroids, vol. 65, no. 5, pp. 266-274. https://doi.org/10.1016/S0039-128X(99)00109-9
Tuba, Zoltán ; Bardin, C. Wayne ; Dancsi, Anna ; Francsics-Czinege, Erzsébet ; Molnár, Csaba ; Csörgei, János ; Falkay, G. ; Koide, Samuel S. ; Kumar, Narender ; Sundaram, Kalyan ; Dukát-Abrók, Vilma ; Balogh, Gábor. / Synthesis and biological activity of a new progestogen, 16-methylene- 17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate. In: Steroids. 2000 ; Vol. 65, No. 5. pp. 266-274.
@article{400bac7821f24d8585b55e51c65d3f38,
title = "Synthesis and biological activity of a new progestogen, 16-methylene- 17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate",
abstract = "The progestational activity of second- and third-generation progestins in oral contraceptives were markedly increased by addition of an 18-methyl group. A new progestin, the 18-methyl analog of Nestorone, 16-methylene-17α- hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate (10), was synthesized. The relative binding affinity and biologic activity of 10 was compared with Nestorone, levonorgestrel, and progesterone using a binding assay for rat progesterone receptors, the Clauberg assay in the rabbit, and by assessing pregnancy maintenance in the rat. These studies, as summarized in Table 4, show that 10 is three to ten times more potent than Nestorone. The addition of the 18-methyl group to Nestorone markedly increased its potency as noted above, but is unlikely to change its rate of delivery from sustained release systems. 10 should be ideally suited for administration by implants or small skin patches. (C) 2000 Elsevier Science Inc.",
keywords = "16-methylene-17α-hydroxy-18-methyl-19-norpregn-4-ene-3, 20- dione acetate, Clauberg assay, Nestorone, Progestin, Synthesis",
author = "Zolt{\'a}n Tuba and Bardin, {C. Wayne} and Anna Dancsi and Erzs{\'e}bet Francsics-Czinege and Csaba Moln{\'a}r and J{\'a}nos Cs{\"o}rgei and G. Falkay and Koide, {Samuel S.} and Narender Kumar and Kalyan Sundaram and Vilma Duk{\'a}t-Abr{\'o}k and G{\'a}bor Balogh",
year = "2000",
month = "5",
doi = "10.1016/S0039-128X(99)00109-9",
language = "English",
volume = "65",
pages = "266--274",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",
number = "5",

}

TY - JOUR

T1 - Synthesis and biological activity of a new progestogen, 16-methylene- 17α-hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate

AU - Tuba, Zoltán

AU - Bardin, C. Wayne

AU - Dancsi, Anna

AU - Francsics-Czinege, Erzsébet

AU - Molnár, Csaba

AU - Csörgei, János

AU - Falkay, G.

AU - Koide, Samuel S.

AU - Kumar, Narender

AU - Sundaram, Kalyan

AU - Dukát-Abrók, Vilma

AU - Balogh, Gábor

PY - 2000/5

Y1 - 2000/5

N2 - The progestational activity of second- and third-generation progestins in oral contraceptives were markedly increased by addition of an 18-methyl group. A new progestin, the 18-methyl analog of Nestorone, 16-methylene-17α- hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate (10), was synthesized. The relative binding affinity and biologic activity of 10 was compared with Nestorone, levonorgestrel, and progesterone using a binding assay for rat progesterone receptors, the Clauberg assay in the rabbit, and by assessing pregnancy maintenance in the rat. These studies, as summarized in Table 4, show that 10 is three to ten times more potent than Nestorone. The addition of the 18-methyl group to Nestorone markedly increased its potency as noted above, but is unlikely to change its rate of delivery from sustained release systems. 10 should be ideally suited for administration by implants or small skin patches. (C) 2000 Elsevier Science Inc.

AB - The progestational activity of second- and third-generation progestins in oral contraceptives were markedly increased by addition of an 18-methyl group. A new progestin, the 18-methyl analog of Nestorone, 16-methylene-17α- hydroxy-18-methyl-19-norpregn-4-ene-3,20-dione acetate (10), was synthesized. The relative binding affinity and biologic activity of 10 was compared with Nestorone, levonorgestrel, and progesterone using a binding assay for rat progesterone receptors, the Clauberg assay in the rabbit, and by assessing pregnancy maintenance in the rat. These studies, as summarized in Table 4, show that 10 is three to ten times more potent than Nestorone. The addition of the 18-methyl group to Nestorone markedly increased its potency as noted above, but is unlikely to change its rate of delivery from sustained release systems. 10 should be ideally suited for administration by implants or small skin patches. (C) 2000 Elsevier Science Inc.

KW - 16-methylene-17α-hydroxy-18-methyl-19-norpregn-4-ene-3

KW - 20- dione acetate

KW - Clauberg assay

KW - Nestorone

KW - Progestin

KW - Synthesis

UR - http://www.scopus.com/inward/record.url?scp=0034037316&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034037316&partnerID=8YFLogxK

U2 - 10.1016/S0039-128X(99)00109-9

DO - 10.1016/S0039-128X(99)00109-9

M3 - Article

VL - 65

SP - 266

EP - 274

JO - Steroids

JF - Steroids

SN - 0039-128X

IS - 5

ER -