Supersteroids Part 2: BA-36644

History:
Ciba was – famously – the company responsible for the introduction of the most popular synthetic steroid of all time; Dianabol, in 1959. Their contribution to the field of steroids also included work on the total synthesis of aldosterone, and new techniques for the synthesis of 19-nor compounds and corticosteroids. They performed clinical evaluations on boldenone undecyclenate (then known by its internal moniker of BA-29038), [1] and they also did some more unusual structural modifications to steroids, testing several “abeo” steroids. [2]

Steroids. 1996 Aug;61(8):492–503. [2]

Though the abeo-prednisolone proved in clinical trials to be no more effective an anti-inflammatory than prednisolone, another experimental “abeo” drug – in this case an anabolic steroid – demonstrated activity significantly different to that of its parent hormone. So significant, in fact, that it deserves “supersteroid” status.

Structure:

Nomenclature:
A-nor-B-homo-7α-17α-dimethylestran-17β-ol-3,6-dione and
A-nor-B-homo-7α-17α-dimethylestr-5-ene-6,17b-dihydroxy-3-one
or
17b-hydroxy-7a,17a-dimethyl-A-nor-B-homoestrane-3,6-dione and
6,17b-dihydroxy-7a,17a-dimethyl-A-nor-B-homo-Δ5-estrene-3-one
or
17b-hydroxy-4-nor-7b-homo-7α,17α-dimethylestra-3,6-dione

Synonyms:
BA-36644
CIBA 36,644-Ba

Structure:
Unlike most steroids, which have six-membered A, B, and C rings, BA-36644 has an expanded (seven-membered) B ring and the A ring is contracted to a five membered (pentacyclic) ring. The prefixes homo and nor describe the ring expansion and ring contraction, respectively.

It is easier to understand this as simply the migration of the bond that joins C10 and C5, to joining C10 and C4. Compounds that arise from bond migration in this way can be given the prefix abeo.
The steroid BA-36644 could be described as 10(5→4)abeo-6-oxo-mibolerone.

mibolerone and BA-36644

Mibolerone (L) and BA-36644 (R)

BA-36644 exists as an equilibrium mixture of two steroids; A-nor-B-homo-7α-17α-dimethylestran-17β-ol-3,6-dione and A-nor-B-homo-7α-17α-dimethylestr-5-ene-6,17b-dihydroxy-3-one. The 6-ketone is unstable and spontaneously rearranges to the enol (5-ene-6-ol) tautomer, and vice-versa.

There are some structural similarities between this drug and the plant hormones brassinolides. 28-homobrassinolide (which, like BA-36644, has a 7-membered B-ring, and a 6-keto function) has recently been found to increase protein synthesis, strength, and lean mass in rats – despite not binding to the androgen receptor. [3]

28-Homobrassinolide (L) and BA-36644 (R).

Anabolic/Androgenic Ratio:
As is typical, tests on the growth response of the levator ani and seminal vesicle in castrated rats were conducted by the Ciba researchers, to measure the anabolic and androgenic responses to the drug. The results themselves, however, were far from typical.

Proc Int Congr Horm Steroids 32:541–547 [4]

This potency of “375-700 times more anabolic than methyltestosterone” while being only 5-10 times as androgenic, would give it an anabolic:androgenic figure of 37,500-70,000:500-1,000 were it to be listed in Vida’s Androgens and Anabolic Agents.

Though it isn’t in Vida’s book, it is mentioned in the 1969 review “Androgenic and Anabolic Steroids” by senior Searle researcher Paul Klimstra, where he observes that it is around 300 times stronger than methyltestosterone. [5]

Intra-science Chemistry Reports. 1969; 3(1-2):92. [5]

Effects:
Male rats given 3mg/kg (a very high dose) for 28 days gained 38% more weight than control animals.

“Daily oral doses of 3mg/kg, administered for 28 days, stimulate body weight gain by 38% in males and 29% in females as compared with controls” [4]

BA-36,644:

  • Has no estrogenic effects. [4]

Proc Int Congr Horm Steroids 32:541–547 [4]

  • Does not cause water retention or electrolyte imbalance. [4]

Proc Int Congr Horm Steroids 32:541–547 [4]

  • Does not affect liver function in dogs or rats. [4]

Proc Int Congr Horm Steroids 32:541–547 [4]

“Furthermore, CIBA 36,644-Ba appears to be well tolerated by the liver. In rats, in doses which – as far as such a comparison is possible – are greatly in excess of the oral anabolic dose, it has no effects on the serum transaminases or on alkaline phosphatase after four weeks of treatment. In dogs treated under similar conditions, it has no effect whatsoever on any of the parameters of liver function chosen.” [4]

Annual Reports in Medicinal Chemistry. Academic Press; 1971. pp171-172.

References:
[1] D ASDM, Papanayiotou P, Marketos S. Renal effects of a new anabolic steroid (29’038-Ba) in old age. Pharmacol. Clin. 1968 Oct 1;1(2):43–6.
[2] Heusler K, Kalvoda J. Between basic and applied research: Ciba’s involvement in steroids in the 1950s and 1960s. Steroids. 1996 Aug;61(8):492–503.
[3] Esposito D, Komarnytsky S, Shapses S, Raskin I. Anabolic effect of plant brassinosteroid. FASEB J. 2011 Oct 1;25(10):3708–19.
[4] Desaulles PA, Schärr B (1967) Properties of a new highly active anabolic steroid CIBA 36,644-Ba. Proc Int Congr Horm Steroids 32:541–547.
[5] Klimstra, P.D. Androgenic and Anabolic Steroids. Intra-science Chemistry Reports. Intra-Science Research Foundation. 1969; 3(1-2):92.

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