83-43-2 Usage
Chemical Properties
White to Off-White Crystalline Powder
Originator
Medrol,Upjohn,US,1957
Uses
Different sources of media describe the Uses of 83-43-2 differently. You can refer to the following data:
1. A glucocorticoid which displays anti-inflamatory and antioxidant properties and attenuates apoptosis in oligodendrocytes after injury. 6α-Methyl Prednisolone is neuroprotective.
2. A glucocorticoid
Definition
ChEBI: The 6alpha-stereoisomer of 6-methylprednisolone.
Manufacturing Process
The following process description is taken from US Patent 2,897,218. Six 100-
ml portions of a medium in 250-ml Erlenmeyer flasks containing 1% glucose,
2% corn steep liquor (60% solids) and tap water was adjusted to a pH of 4.9.
This medium was sterilized for 45 minutes at 15 psi pressure and inoculated
with a one to two day growth of Septomyxa affinis ATCC 6737. The
Erlenmeyer flasks were shaken at room temperature at about 24°C for a
period of 3 days.At the end of this period, this 600-ml volume was used as an inoculum for ten
liters of the same glucose-corn steep liquor medium which in addition
contained 10 ml of an antifoam (a mixture of lard oil and octadecanol). The
fermentor was placed into the water bath, adjusted to 28°C, and the contents
stirred (300 rpm) and aerated (0.5 liter air/10 liters beer). After 17 hours of
incubation, when a good growth developed and the acidity rose to pH 6.7, 2 g
of 6α-methylhydrocortisone plus 1 g of 3-ketobisnor-4-cholen-22-al, dissolved
in 115 ml of dimethylformamide, was added and the incubation (conversion)
carried out at the same temperature and aeration for 24 hours (final pH 7.9).The mycelium (56 g dry weight) was filtered off and the steroidal material was
extracted with methylene chloride, the methylene extracts evaporated to
dryness, and the resulting residue chromatographed over a Florisil column.
The column was packed with 200 g of Florisil and was developed with five
400-ml fractions each of methylene chloride, Skellysolve B-acetone mixtures
of 9:1, 8:2, 7:3, 1:1, and methanol. The fraction eluted with Skellysolve Bacetone (7:3) weighed 1.545 g and on recrystallization from acetone gave, in
three crops, 928 mg of product of MP 210° to 235°C. The sample prepared for
analysis melted at 245° to 247°C.
Therapeutic Function
Glucocorticoid
General Description
Methylprednisolone, 11β,17,21-trihydroxy-6α-methyl-1,4-pregnadiene-3,20-dione, isavailable unmodified or as ester derivatives.Methylprednisolone acetate, USPMethylprednisolone sodium succinate, USP.
Biological Activity
methylprednisolone is a synthetic glucocorticoid receptor agonist, used to achieve prompt suppression of inflammation.cllinical trials: in patients with acute spinal cord injury diagnosed in national acute spinal cord injury study (nascis) centers within 8 hours of injury, methylprednisolone treatment for 48 hours improved motor recovery at 6 weeks (p= 0.09) and 6 months (p= 0.07) after injury[6]. in patients with acute spinal-cord injury, methylprednisolone (30 mg/kg) followed by infusion at 5.4 mg/kg/hour for 23 hours improved neurologic recovery. among patients treated with methylprednisolone (30 mg/kg), mortality at 14 days was significantly increasedsecondary infection[7]. methylprednisolone has entered
Mechanism of action
Methylprednisolone is an analog of prednisolone that exhibits a more prolonged effect
than prednisolone and cortisone; it has practically no mineralocorticosteroid activity and
is better tolerated.
Clinical Use
Adding a 6α-methyl group to prednisolone increases the glucocorticoid activity and effectively
abolishes mineralocorticoid action. It has fivefold the glucocorticoid activity of hydrocortisone
(prednisolone has fourfold the glucocorticoid activity) and none of its mineralocorticoid
properties. It is used almost exclusively as a systemic product and is available as the free alcohol
for oral administration and as various esters.
Safety Profile
Moderately toxic by
intraperitoneal route. A steroid hormone.
Human systemic effects include arrhythmias,
blood pressure lowering, heart rate changes,
increased body temperature, pulse rate
increase, respiratory depression. When heated to decomposition it emits acrid
smoke and irritating fumes.
Synthesis
Methylprednisolone, 11β,17α,21-trihydroxy-6α-methylpregna-1,
4-dien-3,20-dione (27.1.38), differs from prednisolone in the presence of a methyl group at
position C6 of the steroid skeleton of the molecule. This seemingly simple difference in structure
requires a different approach to synthesis. It is synthesized from hydrocortisone (27.1.8),
the carbonyl group of which initially undergoes ketalization by ethylene glycol in the presence
of traces of acid, during which the double bond at position C4– C5 is shifted to position C5– C6,
giving the diethyleneketal 27.1.34. The product is oxidized to an epoxide (27.1.35) using perbenzoic
acid. Next, the resulting epoxide is reacted with methylmagnesium bromide, and subsequent
removal of the ketal protection by hydrogen reduction gives the 5-hydroxy-6-methyl
derivative of dihydrocortisone 27.1.36. The resulting β-hydroxyketone is dehydrated using an
alkaline, and then the resulting 6α-methylcortisone (27.1.37) undergoes microbiological
dehydration at position C1–C2, giving the desired methylprednisolone (27.1.38).
in vitro
methylprednisolone (2-10 mg/kg) significantly inhibited tnf production. high doses of methylprednisolone (50 mg/kg) increased lps-induced il-10 levels. methylprednisolone (0.01-100 μg/ml) increased the biosynthesis of il-10 in lps-activated mouse peritoneal macrophages [1]. in wg patients and controls, methylprednisolone (mp) down-regulated the spontaneous and the staphylococcal enterotoxin b (seb)-induced release of chemokines from peripheral blood mononuclear cells (pbmc)[2]. treatment with 0.25 mm methylprednisolone inhibited acantholysis in skin cultures directly [3].
in vivo
methylprednisolone (30 mg/kg, i.v.) given immediately after sci reduced tnf-α expression by 55% (p<0.01) and nf-kb binding activity. methylprednisolone suppressed the post-traumatic inflammatory activity caused by tnf-alpha-nf-kb cascade[4]. intravenously administration of mp (30 mg/kg) reduced the number of ed1-positive cells by 82% in the rostral cord stump and 66% in the caudal stump. in the adult rat, mp administration shortly after spinal cord transection resulted in a long-term reduction of ed1-positive cells and spinal tissue loss, reduced dieback of vestibule spinal fibres, and a transient sprouting of vestibule spinal fibres near the lesion at 1 and 2 weeks post-lesion. mp treatment also significantly reduced the tissue loss in both cord stumps at 2, 4 and 8 week post-injury[5].
Drug interactions
Metabolism in the liver occurs primarily via the CYP3A4
enzyme to inactive metabolites, which are excreted in the
urine Aldesleukin: avoid concomitant use.
Antibacterials: metabolism accelerated by rifampicin;
metabolism inhibited by erythromycin and possibly
clarithromycin; concentration of isoniazid possibly
reduced.
Anticoagulants: efficacy of coumarins and
phenindione may be altered.
Antiepileptics: metabolism accelerated by
carbamazepine, fosphenytoin, phenobarbital,
phenytoin and primidone.
Antifungals: increased risk of hypokalaemia with
amphotericin - avoid; metabolism inhibited by
ketoconazole and possibly itraconazole.
Antivirals: concentration possibly increased by
ritonavir.
Ciclosporin: rare reports of convulsions in patients
on ciclosporin and high-dose corticosteroids;
levels of ciclosporin increased with high dose
methylprednisolone.
Cobicistat: concentration possibly increased by
cobicistat.
Diuretics: enhanced hypokalaemic effects of
acetazolamide, loop diuretics and thiazide diuretics.
Vaccines: high dose corticosteroids can impair
immune response to vaccines; avoid with live
vaccines.
Metabolism
Metabolism in the liver occurs primarily via the CYP3A4
enzyme to inactive metabolites, which are excreted in the
urine
Purification Methods
Recrystallise medrol from EtOAc. The UV has max at in 95% EtOH 243nm ( 14,875). The 21-acetoxy derivative has m 205-208o (from EtOAc), and [] D +95o ( c 1, CHCl3). [Spero et al. J Am Chem Soc 78 6213 1956; Fried et al. J Am Chem Soc 81 1235 1959; 1H NMR: Slomp & McGarvey J Am Chem Soc 81 2200 1959, Beilstein 8 IV 3498.]
references
[1] marchant a, amraoui z, gueydan c, et al. methylprednisolone differentially regulates il‐10 and tumour necrosis factor (tnf) production during murine endotoxaemia[j]. clinical & experimental immunology, 1996, 106(1): 91-96.[2] torheim e a, yndestad a, bjerkeli v, et al. increased expression of chemokines in patients with wegener's granulomatosis modulating effects of methylprednisolone in vitro[j]. clinical & experimental immunology, 2005, 140(2): 376-383.[3] swanson d l, dahl m v. methylprednisolone inhibits pemphigus acantholysis in skin cultures[j]. journal of investigative dermatology, 1983, 81(3): 258-260.[4] xu j, fan g, chen s, et al. methylprednisolone inhibition of tnf-α expression and nf-kb activation after spinal cord injury in rats[j]. molecular brain research, 1998, 59(2): 135-142.[5] oudega m, vargas c g, weber a b, et al. [j]. european journal of neuroscience, 1999, 11(7): 2453-2464.long‐term effects of methylprednisolone following transection of adult rat spinal cord[6] bracken m b, shepard m j, holford t r, et al. administration of methylprednisolone for 24 or 48 hours or tirilazadmesylate for 48 hours in the treatment of acute spinal cord injury: results of the third national acute spinal cord injury randomized controlled trial[j]. jama, 1997, 277(20): 1597-1604.[7] bracken m b, shepard m j, collins w f, et al. a randomized, controlled trial of methylprednisolone or naloxone in the treatment of acute spinal-cord injury: results of the second national acute spinal cord injury study[j]. new england journal of medicine, 1990, 322(20): 1405-1411.
Check Digit Verification of cas no
The CAS Registry Mumber 83-43-2 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 8 and 3 respectively; the second part has 2 digits, 4 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 83-43:
(4*8)+(3*3)+(2*4)+(1*3)=52
52 % 10 = 2
So 83-43-2 is a valid CAS Registry Number.
InChI:InChI=1/C22H30O5/c1-12-8-14-15-5-7-22(27,18(26)11-23)21(15,3)10-17(25)19(14)20(2)6-4-13(24)9-16(12)20/h4,6,9,12,14-15,17,19,23,25,27H,5,7-8,10-11H2,1-3H3/t12-,14?,15?,17-,19?,20-,21-,22-/m0/s1
83-43-2Relevant articles and documents
Kinetics of drug release from a hyaluronan-steroid conjugate investigated by NMR spectroscopy
Taglienti, Anna,Sequi, Paolo,Valentini, Massimiliano
, p. 245 - 249 (2009)
The methylprednisolone steroid ester of hyaluronan was hydrolyzed under physiological conditions in vitro, and the kinetics of drug release was investigated by NMR spectroscopy. Transverse relaxation times are correlated with the molecular rotational free
Method for reducing or preventing transplant rejection in the eye and intraocular implants for use therefor
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, (2008/06/13)
Methods for reducing or preventing transplant rejection in the eye of an individual are described, comprising: a) performing an ocular transplant procedure; and b) implanting in the eye a bioerodible drug delivery system comprising an immunosuppressive agent and a bioerodible polymer.
High molecular weight prodrug derivatives of antiinflammatory drugs
-
, (2008/06/13)
Compounds of the formula 1, PS - O - A - (CH2)n- B - D (1), wherein PS-O represents an alkoxide residue of any of the free hydroxy groups of a polysaccharide (PS-OH) compound with molecular weight (Mw) of from 40,000 to 5,000,000 selected from dextran, carboxymethyl dextran, diethylaminoethyl dextran, starch, hydroxyet-hyl starch, alginates, glycogen, pullullan, agarose, cellulose, chitosan, chitin and carrageenan,A is a carbonyl group or absent,n is zero or a positive integer from 1 to 14,B is oxygen, a carbonyl group, NR wherein R is hydrogen or lower alkyl, or B is absent, and, D is (i) a group of the formula:, R1 - CO - (11), wherein R1-CO- represents the acyl residue of a carboxylic acid drug (R1-COOH) used in the treatment of inflammatory disorders; or (ii) a group of the formula:, R2 - O - (12), wherein R2-O- refers to the C-21 alkoxide residue of a known antiinflammatory steroid (R2-OH) or an alkoxide residue of any other drug or medicament containing a hydroxy functional group used in the treatment of inflammatory disorders; with the proviso that when A is absent, n is 0, and B is absent, then R1-CO- is different from the acyl residue of acetylsalicylic acid;, and non-toxic pharmaceutically acceptable acid addition salts thereof;, and non-toxic pharmaceutically acceptable cation salts thereof. Such compounds are biolabile prodrugs providing controlled release and prolonged duration of action of the parent active antiinflamma-tory agents locally at the administration site after intra-articular, intra-muscular, subcutaneous or extra-dural application while at the same time being highly stable in aqueous solution in the pH range 3--5. After oral administration of such prodrugs the parent drug is liberated selectively in the terminal ileum and the colon over an extended period of time.