DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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Ixabepilone, 219989-84-1 cas
(1R,5S,6S,7R,10S,14S,16S)-6,10-dihydroxy-1,5,7,
9,9-pentamethyl-14-[(E)-1-(2-methyl-1,3-thiazol-
4-yl)prop-1-en-2-yl]-17-oxa-13-azabicyclo[14.1.0]
heptadecane-8,12-dione
Ixabepilone (INN; also known as azaepothilone B, codenamed BMS-247550) is an epothilone B analog developed byBristol-Myers Squibb as a chemotherapeutic medication for cancer.
It is produced by Sorangium cellulosum.
It acts to stabilize microtubules. It is highly potent agent, capable of damaging cancer cells in very low concentrations, and retains activity in cases where tumor cells are insensitive to paclitaxel.
On October 16, 2007, the U.S. Food and Drug Administration approved ixabepilone for the treatment of aggressive metastaticor locally advanced breast cancer no longer responding to currently available chemotherapies. In November 2008, the EMEAhas refused a marketing authorisation for Ixabepilone.
Ixabepilone is administered through injection, and is marketed under the trade name Ixempra.
patent approval expiry
| United States | 7312237 | 2004-08-21 | 2024-08-21 |
| United States | 6605599 | 1998-05-26 | 2018-05-26 |
| Applicant | Tradename | Generic Name | Dosage | NDA | Approval Date | Type | RLD | US Patent No. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Bristol Myers Squibb
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IXEMPRA KIT
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ixabepilone
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INJECTABLE;IV (INFUSION) | 022065 | Oct 16, 2007 | RX | Yes | RE41911*PED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Bristol Myers Squibb
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IXEMPRA KIT
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ixabepilone
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INJECTABLE;IV (INFUSION) | 022065 | Oct 16, 2007 | RX | Yes | RE41393*PED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Bristol Myers Squibb
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IXEMPRA KIT
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ixabepilone
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INJECTABLE;IV (INFUSION) | 022065 | Oct 16, 2007 | RX | Yes | 7,312,237*PED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Bristol Myers Squibb
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IXEMPRA KIT
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ixabepilone
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INJECTABLE;IV (INFUSION) | 022065 | Oct 16, 2007 | RX | Yes | 7,125,899*PED | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent No | Patent Expiry | patent use code |
|---|---|---|
| 6670384 | Jan 23, 2022 | U-959 |
| 6670384 | Jan 23, 2022 | U-960 |
| 6670384*PED | Jul 23, 2022 | |
| 7022330 | Jan 23, 2022 | U-958 |
| 7022330*PED | Jul 23, 2022 | |
| 7125899 | May 26, 2018 | U-957 |
| 7125899*PED | Nov 26, 2018 | |
| 7312237 | Aug 21, 2024 | U-965 |
| 7312237*PED | Feb 21, 2025 | |
| RE41393 | Feb 8, 2022 | U-961 |
| RE41393*PED | Aug 8, 2022 | |
| RE41911 | Sep 28, 2020 | U-961 |
| RE41911*PED | Mar 28, 2021 |
| Exclusivity Code | ExclusivityDate |
|---|---|
| NCE | Oct 16, 2012 |
| PED | Apr 18, 2015 |
| M-61 | Oct 18, 2014 |
| PED | Apr 16, 2013 |
| Exclusivity Code | ExclusivityDate |
|---|---|
| NCE | Oct 16, 2012 |
Ixabepilone, in combination with capecitabine, has demonstrated effectiveness in the treatment of metastatic or locally advanced breast cancer in patients after failure of an anthracycline and a taxane.
It has been investigated for use in treatment of non-Hodgkin’s lymphoma. In pancreatic cancer phase two trial it showed some promising results (used alone). Combination therapy trials are ongoing.
Ixabepilone is an anti cancer agent acting as a microtubule inhibitor, and which in particular are efficient in the treatment of cancer not reacting to other anti cancer agents, such as e.g. paclitaxel. Ixabepilone is marketed under the trade name Ixempra® and are approved for the treatment of aggressive metastatic or locally advanced breast cancer which not responding to the current prevailing chemotherapies.
Ixabepilone known under the CAS no. 219989-84-1 has the following structure:
Ixabepilone
Ixabepilone may be prepared from a starting material named epothilone B having the structural formula:
Epothilone B Ixabepilone as a compound is described in the USRE4191 1. USRE4191 1 furthermore disclose a process for synthesizing Ixabepilone.
The US 6,365,749 describes a process for making ixabepilone by reacting epothilone B with a palladium catalyst in the presence of a nucleophilic donor.
The USRE39356 do also describe a process for making Ixabepilone by reacting epothilone B with an azide donor agent and a reducing agent in the presence of a phase transfer catalyst and a palladium catalyst.
Ixabepilone is the treatment of metastatic and advanced breast cancer drugs.Ixabepilone as anticancer drugs alone or in combination with capecitabine (Capecitabine) in combination. October 16, 2007 approved for marketing by the FDA, trade name Ixempra, by the Bristol-Myers Squibb Company’s development.
Ixabepilone is an anti-mitotic drugs that are inhibitors of tubulin, the mechanism and paclitaxel (Taxol) the same class of drugs. Epothilone (Epothilone) by colistin (myxobacterium) Sorangium cellulosum fermentation of several macrolide metabolites in general. Anticancer activity in vitro experiments, epothilone A and epothilone B showed good activity, even in the paclitaxel-resistant cells also showed good activity. But its activity in vivo experiments in general, this is probably due to the body of the ester hydrolases that macrolide ring opening induced inactivation. In a series of epothilone derivatives activity test, it was found with the lactam bond instead of the original product of ester bonds – ixabepilone anticancer activity can be well retained.
Ixabepilone is epothilone B semi-synthetic derivatives. Epothilone B is a macrocyclic lactone, a hydroxyl moiety is allyl alcohol, the Pd catalyst can be obtained by ring-opening Pd complexes 1 , 1 received azide nucleophile attacking the anion generated with three azide product phosphorus reduction to give methyl amino acids 2 . Here we must point out that the attack was completely azide stereoselectivity, which is determined by two consecutive trans-attack lead, Pd (0)-trans lactone generate offensive allyl Pd complexes, to accept anti-azide anion type attack, to maintain the configuration of the product obtained. Amino acids 2 HoBt and EDCI generated by an amide bond to get ixabepilone.
IXEMPRA (ixabepilone) is a microtubule inhibitor belonging to a class of antineoplastic agents, the epothilones and their analogs. The epothilones are isolated from the myxobacterium Sorangium cellulosum. Ixabepilone is a semisynthetic analog of epothilone B, a 16-membered polyketide macrolide, with a chemically modified lactam substitution for the naturally existing lactone.
The chemical name for ixabepilone is (1S,3S,7S,10R,11S,12S,16R)-7,11dihydroxy-8,8,10,12,16-pentamethyl-3-[(1E)-1-methyl-2-(2-methyl-4-thiazolyl)ethenyl]17-oxa-4-azabicyclo[14.1.0] heptadecane-5,9-dione, and it has a molecular weight of 506.7. Ixabepilone has the following structural formula:
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IXEMPRA (ixabepilone) for injection is intended for intravenous infusion only after constitution with the supplied DILUENT and after further dilution with a specified infusion fluid . IXEMPRA (ixabepilone) for injection is supplied as a sterile, non-pyrogenic, single-use vial providing 15 mg or 45 mg ixabepilone as a lyophilized white powder. The DILUENT for IXEMPRA is a sterile, non-pyrogenic solution of 52.8% (w/v) purified polyoxyethylated castor oil and 39.8% (w/v) dehydrated alcohol, USP. The IXEMPRA (ixabepilone) for injection and the DILUENT for IXEMPRA are co-packaged and supplied as IXEMPRA Kit.
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DR ANTHONY MELVIN CRASTO Ph.D
New Drug Approvals 
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