Sunday 14 September 2014

Highly regioselective lithiation of pyridines bearing an oxetane unit by n-butyllithium,


GA

G. Rouquet, D.C. Blakemore, S.V. Ley,Chem. Comm.2014, 50, 8908-8911
The first regioselective ortho-lithiation at the 4-position of simple pyridine derivatives containing a 3-oxetane unit has been achieved using n-butyllithium as base. Electrophilic quenching of the resulting lithio species provides a rapid access to a broad range of new functionalized pyridine oxetane building blocks.

Monday 8 September 2014

Tecadenoson…………Atrial Fibrillation

Tecadenoson

Tecadenoson
CAS : 204512-90-3
N-[(3R)-Tetrahydro-3-furanyl]adenosine
(2R,3S,4R,5R)-2-(hydroxymethyl)-5-[6-[[(3R)-oxolan-3-yl]amino]purin-9-yl]oxolane-3,4-diol
Manufacturers’ Codes: CVT-510
UNII-GZ1X96601Z; AC1L4KMO;
Molecular Formula: C14H19N5O5
Molecular Weight: 337.33
Percent Composition: C 49.85%, H 5.68%, N 20.76%, O 23.71%
Therap-Cat: Antiarrhythmic.
Tecadenoson is a novel selective A1 adenosine receptor agonist that is currently being evaluated for the conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. It is being developed by CV Therapeutics, Inc.
Tecadenoson is an adenosine A1 agonist which had been in phase II clinical evaluation by Gilead Sciences for treatment of atrial fibrillation. The company was also conducting phase III clinical trials for the treatment of paroxysmal supraventricular tachycardia (PSVT); however, no recent developments have been reported for these indications.
Due to the fact that tecadenoson selectively stimulates the A1 receptor and slows electrical impulses in the heart’s conduction system without significantly stimulating the A2 receptor, the intravenous administration of CVT-510 may hold potential for rapid intervention in the control of atrial arrhythmias without lowering blood pressure.
The reaction of 3-tetrahydrofuroic acid (I) with diphenyl phosphoryl azide (DPPA) in refluxing dioxane gave the intermediate isocyanate (II), which was treated with benzyl alcohol (III) to yield carbamate (IV). Subsequent hydrogenolysis in the presence of Pd/C afforded racemic amine (V), which was resolved by treatment with S-(+)-10-camphorsulfonyl chloride (VI) in pyridine, followed by column chromatography and recrystallization from acetone of the resulting sulfonamide (VII). Then, hydrolysis in HCl-AcOH provided the S-amine (VIII). Condensation of amine (VIII) with 6-chloropurine riboside (IX) in the presence of triethylamine in refluxing MeOH furnished the title compound.
EP 0920438; EP 0992510; JP 2000501426; US 5789416; WO 9808855
……………………………
………………………….
CVT-510 (tecadenoson) has chemical structure (8 :
Figure imgf000011_0002
…………………………………….
Compound I can be prepared through reaction of the corresponding primary amino compound, R1NH2, through heating with commercially available 6-chloroadenosine in the appropriate solvent (e.g. n-butanol, dimethylformamide, and ethanol). The primary amino compound, R1NH2, is either commercially available or can be prepared as previously described (International Patent Application WO 98/08855).
Figure US06576619-20030610-C00008
 ……………………………
EXAMPLE 1
The compounds of this invention may be prepared by conventional methods of organic chemistry. The reaction sequence outlined below, is a general method, useful for the preparation of compounds of this invention.
Figure imgf000015_0001
Figure imgf000015_0002
According to this method, oxacycloalkyl carboxylic acid is heated in a mixture of dioxane, diphenylphosphoryazide and triethylamine for 1 hour. To this mixture is added benzyl alcohol and the reaction is further heated over night to give intermediate compound 1. Compound 1 is dissolved in methanol. Next, concentrated HC1, Pd/C is added and the mixture is placed under hydrogen at 1 atm. The mixture is stirred overnight at room temperature and filtered. The residue is recrystallized to give intermediate compound 2. 6-chloropurine riboside is combined and the mixture is compound 2 dissolved in methanol and treated with triethylamine. The reaction is heated to 80° C for 30 hours. Isolation and purification leads to Compound 3.
EXAMPLE 2
Compounds of this invention prepared according to the method of Example 1 were tested in two functional models specific for adenosine A, receptor agonist function. The first was the A , receptor mediated inhibition of isoproterenol stimulated cAMP accumulation in DDT cells. The EC50 of each derivative is shown in Table I. Also shown in Table I is the ability of each derivative to stimulate cAMP production in PC 12 cells, a function of agonist stimulation of adenosine A2 receptors. The ratio of the relative potency of each compound in stimulating either an A, receptor or an A2 receptor effect is termed the selectivity of each compound for the A, receptor. As can be seen in Table I, each derivative is relatively selective as an A, receptor agonist. The use of measuring cAMP metabolism as an assay for adenosine A , receptor function has been previously described (Scammells, P., Baker, S., Belardinelli, L., and Olsson, R. , 1994, Substituted 1 ,3-dipropylxanthines as irreversible antagonists of A, adenosine receptors. J. Med. Chem 37: 2794-2712, 1994).
Table I
Compound R EC50 (nM) ECS, (nM) A,/A2 A-/A, DDT cells PC 12 cells
I 4-arninopyran 12 970 0.012 80.0
II (±)-3-aminotetrahydrofuran 13 1400 0.0093 107.6
III (R)-3-aminotetrahydrofuran 1.08 448 0.0024 414
IV ( 1 )-caprolactam 161 181 0.889 1.12
V (S)-3-aminotetrahydrofuran 3.40 7680 0.00044 2258
Compounds were also tested in a whole organ model of A, receptor activation with respect to atrial and AV nodal function. In this model, guinea pig hearts are isolated and perfused with saline containing compound while atrial rate and AV nodal conduction time are assessed by electrographic measurement of atrial cycle length and AV intervals, as detailed in Belardinelli, L, Lu, J. Dennis, D. Martens, J, and Shryock J. (1994); The cardiac effects of a novel A,-adenosine receptor agonist in guinea pig isolated heart. J. Pharm. Exp. Therap. 271:1371-1382 (1994). As shown in Figure 1, each derivative was effective in slowing the atrial rate and prolonging the AV nodal conduction time of spontaneously beating hearts in a concentration-dependent manner, demonstrating efficacy as adenosine A, receptor agonists in the intact heart.
EXAMPLE 3
Preparation ofN-benzyloxycarbonyl-4-aminopyran.
A mixture of 4-pyranylcarboxylic acid (2.28 gm, 20 mmol), diphenylphosphorylazide (4.31 ml, 20 mmol), triethylamine (2.78 ml, 20 mmol) in dioxane (40 ml) was heated in a 100° C oil bath under dry nitrogen for 1 hour. Benzyl alcohol (2.7 ml, 26 mmol) was added, and heating was continued at 100° C for 22 hours. The mixture was cooled, filtered from a white precipitate and concentrated. The residue was dissolved in 2N HC1 and extracted twice with EtOAc. The extracts were washed with water, sodium bicarbonate, brine and then dried over MgSO4, and concentrated to an oil which solidified upon standing. The oil was chromatographed (30% to 60% EtO Ac/Hex) to give 1.85 g of a white solid (40%).
Preparation of 4-aminopyran.
N-benzyloxycarbonyl-4-aminopyran (1.85 gm, 7.87 mmol) was dissolved in MeOH (50 ml) along with cone. HC1 and Pd-C ( 10%, 300 mg). The vessel was charged with hydrogen at 1 atm and the mixture was allowed to stir for 18 hours at room temperature. The mixture was filtered through a pad of eelite and concentrated. The residue was co-evaporated twice with MeOH/EtOAc and recrystallized from MeOH/EtOAc to afford 980 mg (91 %) of white needles (mp 228-230° C).
Preparation of 6-(4-aminopyran)-purine riboside. A mixture of 6-chloropurine riboside (0.318 gm, 1. 1 mmol), 4-aminopyran-HCl
(0.220 mg,
1.6 mmol) and triethylamine (0.385 ml, 2.5 mmol) in methanol (10 ml) was heated to 80° C for 30 hours. The mixture was cooled, concentrated and the residue chromatographed (90: 10: 1, CH2 Cl2/MeOH/PrNH2). The appropriate fractions were collected and recliromatographed using a chromatotron
(2 mm plate, 90: 10: 1, CH2 Cl2/MeOH/PrNH2) to give an off white foam (0.37 gm, 95%).
EXAMPLE 4
Preparation of N-benzyloxycarbonyl-3-aminotetrahydrofuran. A mixture of 3-tetrahydrofuroic acid (3.5 gm, 30 mmol), diphenylphosphorylazide (6.82 ml, 32 mmol), triethylamine (5 ml, 36 mmol) in dioxane (35 ml) was stirred at RT for 20 min then heated in a 100° C oil bath under dry nitrogen for 2 hours. Benzyl alcohol (4.7 ml, 45 mmol) was added, and continued heating at 100° C for 22 hours. The mixture was cooled, filtered from a white precipitate and concentrated. The residue was dissolved in 2N HC1 and extracted twice using EtOAc. The extracts were washed with water, sodium bicarbonate, brine dried over MgSO4, and then concentrated to an oil which solidifies upon standing. The oil was chromatographed (30% to 60% EtO Ac/Hex) to give 3.4 g of an oil (51
%).
Preparation of 3-aminotetrahydrofuran.
N-benzyloxycarbonyl-3-aminotetrahydrofuran (3.4 gm, 15 mmol) was dissolved in MeOH (50 ml) along with cone. HC1 and Pd-C (10%, 300 mg). The vessel was charged with hydrogen at 1 atm and the mixture was allowed to stir for 18 hours at room temperature. The mixture was filtered through a pad of celite and concentrated. The residue was co-evaporated two times with MeOH/EtOAc and recrystallized from MeOH/EtOAc to give 1.9 g of a yellow solid.
Preparation of 6-(3-aminotetrahydrofuranyl)purine riboside. A mixture of 6-chloropurine riboside (0.5 gm, 1.74 mmol), 3-aminotetrahydrofuran
(0.325 gm, 2.6 mmol) and triethylamine (0.73 ml, 5.22 mmol) in methanol (10 ml) was heated to 80° C for 40 hours. The mixture was cooled, and concentrated. The residue was filtered through a short column of silica gel eluting with 90/10/1 (CH2Cl2/MeOH/PrNH2), the fractions containing the product were combined and concentrated. The residue was chromatorgraphed on the chromatotron (2 mm plate, 92.5/7.5/1 , CH2CL2/MeOH/P.NH2). The resulting white solid was recrystallized from MeOH/EtOAc to give 0.27 gm of white crystals (mp 128-130° C).
EXAMPLE 5
Resolution of 3-arninotetrahydrofuran hydrochloride
A mixture of 3-aminotetrahydrofuran hydrochloride (0.5 gm, 4 mmol) and
(S)-(+)-10-camphorsulfonyl chloride (1.1 gm, 4.4 mmol) in pyridine (10 ml) was stirred for 4 hours at room temperature and then concentrated. The residue was dissolved in EtOAc and washed with 0.5N HC1, sodium bicarbonate and brine. The organic layer was dried over MgSO4, filtered and concentrated to give 1. 17 g of a brown oil (97%) which was chromatographed on silica gel (25% to 70% EtOAc/Hex). The white solid obtained was repeatedly recrystallized from acetone and the crystals and supernatant pooled until an enhancement of greater than 90% by 1H NMR was acheived.
Preparation of 3-(S)-aminotetrahydrofuran hydrochloride.
The sulfonamide (170 mg, 0.56 mmol) was dissolved in cone. HCl/AcOH (2 mL each), stirred for 20 hours at room temperature, washed three times with CH2C12 (10 ml) and concentrated to dryness to give 75 mg (qaunt ) of a white solid

Preparation of 6-(3-(S)-aminotetrahydrofuranyl)puπne riboside.
A mixture of 6-chloropurιne riboside (30 mg, 0.10 mmol),
3-(S)-amιnotetrahydrofuran hydrochloride (19 mg, 0.15 mmol) and triethylamine (45 ml, 0.32 mmol) in methanol
(0.5 ml) was heated to 80° C for 18 hours. The mixture was cooled, concentrated and chromatographed with 95/5 (CH2Cl /MeOH) to give 8 mg (24%) of a white solid.
Chemical structure for tecadenoson
Literature References:
Selective adenosine A1-receptor agonist. Prepn: R. T. Lum et al., WO 9808855eidemUS5789416 (both 1998 to CV Therapeutics).
Clinical effect on AV nodal conduction: B. B. Lerman et al., J. Cardiovasc. Pharmacol. Ther.6, 237 (2001).
Clinical evaluation in paroxysmal supraventricular tachycardia: E. N. Prystowsky et al., J. Am. Coll. Cardiol. 42, 1098 (2003); K. A. Ellenbogen et al., Circulation 111, 3202 (2005).
Review of pharmacology and clinical experience: A. Zaza, Curr. Opin. Invest. Drugs 3, 96-100 (2002); J. W. Cheung, B. B. Lerman, Cardiovasc. Drug Rev. 21, 277-292 (2003).
US7144871*19 Feb 20035 Dec 2006Cv Therapeutics, Inc.Partial and full agonists of A1 adenosine receptors
US7696181*24 Aug 200613 Apr 2010Cv Therapeutics, Inc.Partial and full agonists of A1 adenosine receptors
Keywords: Antiarrhythmic,  Adenosine Receptor Agonist, Tecadenoson, CVT-510, CV Therapeutics

Infinity and AbbVie partner to develop and commercialise duvelisib for cancer





Duvelisib

Infinity and AbbVie partner to develop and commercialise duvelisib for cancer
INK 1197; IPI 145; 8-Chloro-2-phenyl-3-[(1S)-1-(9H-purin-6-ylamino)ethyl]-1(2H)-isoquinolinone



Molecular Formula
C22H17ClN6O
Molecular Weight
416.86
CAS Registry Number
1201438-56-3

 
Infinity Pharmaceuticals has partnered with AbbVie to develop and commercialise its duvelisib (IPI-145), an oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, to treat patients with cancer. 

 



Infinity Pharmaceuticals has partnered with AbbVie to develop and commercialise its duvelisib (IPI-145), an oral inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K gamma, to treat patients with cancer.
Duvelisib has shown clinical activity against different blood cancers, such as indolent non-Hodgkin's lymphoma (iNHL) and chronic lymphocytic leukemia (CLL).
AbbVie executive vice-president and chief scientific officer Michael Severino said: "We believe that duvelisib is a very promising investigational treatment based on clinical data showing activity in a broad range of blood cancers."
http://www.pharmaceutical-technology.com/news/newsinfinity-abbvie-partner-develop-commercialise-duvelisib-cancer-4363381?WT.mc_id=DN_News 

 

Duvelisib (IPI-145,  INK-1197), an inhibitor of PI3K-delta and –gamma, originated at Takeda subsidiary Intellikine. It is now being developed by Infinity Pharmaceuticals, which began a phase III trial in November, following US and EU grant of orphan drug status for both CLL and small lymphocytic leukemia


more on this drug

http://newdrugapprovals.org/2014/09/09/infinity-and-abbvie-partner-to-develop-and-commercialise-duvelisib-for-cancer-for-the-treatment-of-chronic-lymphocytic-leukemia/

KEY     Duvelisib, IPI-145,  INK-1197, AbbVie, INFINITY

Monday 1 September 2014

A Step Toward Making Painkillers Without Poppies Bioengineering: Modified yeast produce morphine and semisynthetic opioids starting from thebaine

09235-notw4-thebaine
 
Using thebaine as the starting material, the same set of enzymes can catalyze reactions in different pathways leading to either morphine or neomorphine. With the addition of bacterial enzymes, they can produce semisynthetic opioids such as oxycodone. 
 
READ AT.
The supply chain for some of the world’s most prescribed painkillers—natural opioids such as morphine and semisynthetic opioids such as oxycodone—depends on the cultivation of opium poppies, Papaver somniferum. Although poppy farming is a relatively cheap way to obtain the needed materials, it risks diversion to illicit drugs.
 

Drug Assembly On-Site... Drug Delivery: Click reaction links small molecules to form larger potential drug inside cells

09235-notw6-reactioncxd_17863669-690
When a number of derivatized small-molecule inhibitors bind to an RNA repeat sequence in cells, their alkyne and azide groups react with one another, producing potent oligomers.

If a multicomponent bioactive agent is too big to slip into cells, it would be nice to get its components into cells first and then combine them on-site. That’s what Matthew D. Disney, Suzanne G. Rzuczek, and HaJeung Park at Scripps Research Institute Florida did with a potential myotonic dystrophy type 2 (DM2) treatment (Angew. Chem. 2014, DOI: 10.1002/ange.201406465).
DM2 is a rare condition characterized by muscle pain and weakness. It’s caused by a genetic defect that generates toxic RNA with a four-nucleotide repeat pattern.
READ

Sunday 31 August 2014

Idarubicin hydrochloride


 

 

Idarubicin hydrochloride 

NSC-256439, IMI-30, DMDR, Idamycin, Zavedos

 

Idarubicin /ˌdəˈrbɨsɪn/ or 4-demethoxydaunorubicin is an anthracyclineantileukemic drug. It inserts itself into DNA and prevents DNA from unwinding by interfering with the enzyme topoisomerase II. It is an analog of daunorubicin, but the absence of a methoxy group increases its fat solubility and cellular uptake.[1] Similar to other anthracyclines, it also induces histone eviction fromchromatin.[2]
It belongs to the family of drugs called antitumor antibiotics.
It is currently combined with cytosine arabinoside as a first line treatment ofacute myeloid leukemia.
It is distributed under the trade names Zavedos (UK) and Idamycin (USA).
Idarubicin ball-and-stick.png

UV – spectrum

Conditions : Concentration – 1 mg / 100 ml
SOLVENT DESIGNATION SCHEDULEMETHANOL
WATER
0.1 M HCL
0.1M NAOH
The absorption maximum481 nm,
287 nm,
251 nm
484 nm
289 nm
257 nm
484 nm
289 nm
257 nm
Observed
decay
207
179
816
194
180
743
194
180
738
-
ε11100
9540
43600
10400
9620
39700
10400
9620
39400
-

IR – spectrum

WAVELENGTH (ΜM)
WAVENUMBER (CM -1 )

Brief background information

SALTATCFORMULAMMCAS
-L01DB0626 H 27 NO 9497.50 g / mol58957-92-9
Idarubicin is the 4-demethoxy derivative of daunorubicin. Idarubicin is an antineoplastic agent that has been used to treat various cancers, including those of the breast, lung, stomach, ovaries, and lymph system. Idarubicin is marketed as an intravenous injection of Idarubicin hydrochloride of the formula,
Figure imgf000003_0003
under the brand name IDAMYCIN®. Idarubicin hydrochloride is a red-orange crystalline powder, soluble in water, methanol, and other polar solvents like dimethylformamide. It is practically insoluble in acetone, chloroform, and methylene chloride. Idarubicin hydrochloride has a melting point of 175-180°C, and apH of 5.0-6.5 in a 0.5% w/v solution in water.

Application

  • antitumor agent
  • anthracycline antibiotic

Classes of substances

  • Naftatsenovye antibiotics

Synthesis pathway

PREPARATION



SYNTHESIS A)
  1. SYNTHESIS A)
    • US 4,471,052 (ADRIA; 9.11.1984; APPL. 18.1.1982).
SYNTHESIS OF B)
  1. SYNTHESIS OF B)
    • DOS 2,525,633 (SOC. FARMACEUTICI; APPL. 06.09.1975; GB -PRIOR. 16.12.1974).
    •  US 4,046,878 (SOC. FARMACEUTICI; 09/06/1977; APPL. 05/22/1975; GB -PRIOR. 12.6.1974).

The reaction of daunomycinone (IX) with AlCl3 in dichloromethane gives 4-demethyldaunomycinone (X), which is ketalized with ethylene glycol as before yielding the dioxolane (XI). The selective sulfonation of (XI) with TsCl, DIEA and DMAP in pyridine affords the 4-tosyloxy derivative (XII), which is treated with 4-methoxybenzylamine (XIII) in pyridine providing the secondary benzylamine (XIV). Elimination of the benzyl protecting group of (XIV) with TFA gives 4-amino-4-demethoxydaunomycinone ethylene ketal (XV), which is deaminated by reaction with TFA, NaNO2 and H3PO2 to give 4-demethoxydaunomycinone (XVI). Finally, this compound is submitted to fermentation with Streptomyces peucetius corneus, S. Peucetius caesius, S. Caeruleus, S. Peucetius , S. Coeruleorubidus, and other chemical or radio-induced mutants thereof.
Mitscher, LA; Lednicer, D. (Pharmacia Corp.); Biosynthesis of simplified anthracyclines US 4471052.


condensation of chiral tetraline (I) with phthalic anhydride (II) by means of AlCl3 at 180 C gives the naphthacenedione (III),  acetyl group which is ketalized with ethylene glycol and p-toluenesulfonic acid yielding the dioxolane (IV). The hydroxylation of (IV) with Br2 and AIBN in CCl4/CHCl3 affords the 4-demethoxy-7-epidaunomycinone (V), which is isomerized with TFA yielding 4-demethoxydaunomycinone (VI) . The condensation of (VI) with the acylated hexopyranosyl chloride (VII) by means of CF3SO3Ag of Br2Hg affords the trifluoroacetylated 4-demethoxydaunomycin (VIII), which is finally deprotected by treated with NaOH  to eliminate the trifluoroacetyl groups


Trade Names

COUNTRYTRADE NAMEMANUFACTURER
GermanyZavedosPharmacia
France- “-Pfizer
United Kingdom- “-Pharmacia
Italy- “-Pharmacia & Upjohn
JapanIdamitsinPfizer
UkraineZavedosActavis Italy SpA, Italy
IdalekCJSC “Biolik”, Ukraine
ZavedosPfizer Іtaliya Srl, Іtaliya
RubidiumNGO “Lance Farm”, Russia
other generic drugs

Formulations

  • Capsules of 5 mg, 10 mg, 25 mg;
  • vial of 5 mg, 10 mg (hydrochloride)
IDAMYCIN PFS Injection contains idarubicin hydrochloride and is a sterile, semi-synthetic, preservative-free solution (PFS) antineoplastic anthracycline for intravenous use. Chemically, idarubicin hydrochloride is 5, 12-Naphthacenedione, 9-acetyl-7-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxyhydrochloride, (7S-cis). The structural formula is as follows:
Idamycin PFS®  (idarubicin hydrochloride) Structural Formula Illustration
C26H27NO9•Hcl           M.W 533.96
IDAMYCIN PFS (idarubicin hydrochloride injection) is a sterile, red-orange, isotonic parenteral preservative-free solution, available in 5 mL (5 mg), 10 mL (10 mg) and 20 mL (20 mg) single-use-only vials.
Each mL contains Idarubicin HCL, USP 1 mg and the following inactive ingredients: Glycerin, USP 25 mg and Water for Injection, USP q.s. Hydrochloric Acid, NF is used to adjust the pH to a target of 3.5.
Product NameIdarubicin Hydrochloride
Chemical Name(7S,9S)-9-Acetyl-7-[(3-amino-2,3,6-trideoxy-a-L- lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11- trihydroxy-5,12-naphthacenedione hydrochloride
SynonymIdamycin; Zavedos
Formula Wt.533.96
Melting Point183oC-185oC
Purity98%
SolubilitySoluble in water and methanol.
Store Temp-20oC
ReferencesGanzina, F., Pacciarini, MA., Di Pietro, N. Invest New Drugs. 4:85-105 (1986). Tsuruo, T., Oh-Hara, T., Sudo, Y., Naito, M. Anticancer Res. 13:357-61 (1993). Belaud-Rotureau, MA., Durrieu, F., Labroille, G. et al Leukemia 14:1266-75 (2000).


IDARUBICIN
Idarubicin.svg
Idarubicin ball-and-stick.png
SYSTEMATIC (IUPAC) NAME
(1S,3S)-3-acetyl-3,5,12-trihydroxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl 3-amino-2,3,6-trideoxo-α-L-lyxo-hexopyranoside
CLINICAL DATA
AHFS/DRUGS.COMmonograph
MEDLINEPLUSa691004
PREGNANCY CAT.(US)
LEGAL STATUS-only (US)
PHARMACOKINETIC DATA
PROTEIN BINDING97%
HALF-LIFE22 hours
IDENTIFIERS
CAS NUMBER58957-92-9 Yes
ATC CODEL01DB06
PUBCHEMCID 42890
DRUGBANKDB01177
CHEMSPIDER39117 Yes
UNIIZRP63D75JW Yes
KEGGD08062 Yes
CHEBICHEBI:42068 Yes
CHEMBLCHEMBL1117 Yes
SYNONYMS9-acetyl-7-(4-amino-5-hydroxy-6-methyl-tetrahydropyran-2-yl)oxy-6,9,11-trihydroxy-7,8,9,10-tetrahydrotetracene-5,12-dione
CHEMICAL DATA
FORMULAC26H27NO9 
MOL. MASS497.494 g/mol

Links

  1. Synthesis a)
    • US 4,471,052 (Adria; 9.11.1984; appl. 18.1.1982).
  2. Synthesis of b)
    • DOS 2,525,633 (Soc. Farmaceutici; appl. 06.09.1975; GB -prior. 16.12.1974).
    •  US 4,046,878 (Soc. Farmaceutici; 09/06/1977; appl. 05/22/1975;GB -prior. 12.6.1974).
    • UV and IR Spectra. H.-W. Dibbern, RM Muller, E. Wirbitzki, 2002 ECV
    • NIST / EPA / NIH Mass Spectral Library 2008
    • Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman.Academic Press, 2000.
    • Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.

References

  1.  Package insert
  2.  Pang B, Qiao X, Janssen L, Velds A, Groothuis T, Kerkhoven R, Nieuwland M, Ovaa H, Rottenberg S, van Tellingen O, Janssen J, Huijgens P, Zwart W, Neefjes J (2013). “Drug-induced histone eviction from open chromatin contributes to the chemotherapeutic effects of doxorubicin”Nature Communications 4: 1908. doi:10.1038/ncomms2921.PMID 23715267.

External links

Idarubicin

Title: Idarubicin
CAS Registry Number: 58957-92-9
CAS Name: (7S,9S)-9-Acetyl-7-[(3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,9,11-trihydroxy-5,12-naphthacenedione
Additional Names: (1S,3S)-3-acetyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-6,11-dioxo-1-naphthacenyl-3-amino-2,3,6-trideoxy-a-L-lyxo-hexopyranoside; 4-demethoxydaunomycin; 4-demethoxydaunorubicin; DMDR
Manufacturers' Codes: IMI-30; NSC-256439
Molecular Formula: C26H27NO9
Molecular Weight: 497.49
Percent Composition: C 62.77%, H 5.47%, N 2.82%, O 28.94%
Literature References: Orally active anthracycline; analog of daunorubicin, q.v. Prepn: B. Patelli et al. DE 2525633eidem, US4046878 (1976, 1977 both to Soc. Farmac. Ital.); and antitumor activity: F. Arcamone et al., Cancer Treat. Rep. 60, 829 (1976). Total synthesis for larger scale preparation: M. J. Broadhurst et al., Chem. Commun. 1982, 158. Synthesis of optically pure isomers: Y. Kimura et al., Bull. Chem. Soc. Jpn. 59, 423 (1986). Metabolism and biodistribution in rats: G. Zini et al., Cancer Chemother. Pharmacol. 16, 107 (1986). HPLC determn in plasma: S. S. N. De Graaf et al., J. Chromatogr. 491, 501 (1989). Clinical pharmacokinetics: H. C. Gillies et al., Br. J. Clin. Pharmacol. 23, 303 (1987). Clinical evaluation of cardiac toxicity: F. Villani et al., Eur. J. Cancer Clin. Oncol. 25, 13 (1989). Reviews of pharmacology and antitumor efficacy: A. M. Casazza, Cancer Treat. Rep. 63, 835-844 (1979); F. Ganzina et al., Invest. New Drugs 4, 85-105 (1986). Symposium on clinical experience in acute leukemias: Semin. Oncol. 17, Suppl. 2, 1-36 (1989).
 
Derivative Type: Hydrochloride
CAS Registry Number: 57852-57-0
Trademarks: Idamycin (Pharmacia & Upjohn); Zavedos (Pharmacia & Upjohn)
Molecular Formula: C26H27NO9.HCl
Molecular Weight: 533.95
Percent Composition: C 58.48%, H 5.29%, N 2.62%, O 26.97%, Cl 6.64%
Properties: Orange crystalline powder, mp 183-185° (Arcamone); also reported as mp 172-174° (Broadhurst). [a]D20 +205° (c = 0.1 in methanol) (Arcamone); also reported as [a]D20 +188° (c = 0.10 in methanol) (Kimura).
Melting point: mp 183-185° (Arcamone); mp 172-174° (Broadhurst)
Optical Rotation: [a]D20 +205° (c = 0.1 in methanol) (Arcamone); [a]D20 +188° (c = 0.10 in methanol) (Kimura)
 
Therap-Cat: Antineoplastic.
Keywords: Antineoplastic; Antibiotics and Analogs; Anthracyclines; Topoisomerase II Inhibitor.