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Yearly Archives: 2013
FDA Breakthrough Therapy Designation: Second Drug Receives FDA Approval
The FDA approves on November 13, the second drug to have the coveted Breakthrough Therapy Designation (BTD). The approval is for Pharmacyclics’ orphan drug Imbruvica (Ibrutinib) for the treatment of patients with Mantle Cell Lymphoma (MCL), a very rare and aggressive type of blood cancer.
The FDA’s BTD has come through once again, twice within the last 2 weeks. November 1 saw the FDA’s first approval of a BTD for a drug – Genentech’s Gazyva (Obinutuzumab) for the treatment of patients with previously untreated Chronic Lymphocytic Leukemia (CLL).
The FDA approves Imbruvica under its accelerated approval program, which allows the agency to approve a drug to treat a serious or rare disease based on clinical data that shows that “the drug has an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients.” Imbruvica also receives FDA’s Orphan Drug Designation (ODD) and Priority Review.
FDA Regulatory Actions…
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MK 5172 a next Generation HCV NS3/4a Protease Inhibitor

1206524-85-7
Chemical Formula: C29H38N4O7
Exact Mass: 554.27405
Molecular Weight: 554.63462
Elemental Analysis: C, 62.80; H, 6.91; N, 10.10; O, 20.19
IUPAC/Chemical name:
(1aR,5S,8S,10R,22aR)-5-(1,1-Dimethylethyl)-1,1a,3,4,5,6,9,10,18,19,20,21,22,22a-tetradecahydro-14-methoxy-3,6-dioxo-8H-7,10-methanocyclopropa[18,19][1,10,3,6]dioxadiazacyclononadecino[11,12-b]quinoxaline-8-carboxylic acid.
Development of a Practical, Asymmetric Synthesis of the Hepatitis C Virus Protease Inhibitor MK-5172.Org. Lett. 2013;
15: 4174-4177

MK-5172 is a hepatitis C virus protease inhibitor. Key steps in the synthesis depicted are (1) the regioselective SNAr reaction of dichloroquinoxaline A with prolinol derivative B and (2) construction of the 18-membered macrocycle using a macrolactamization (F → G).
Comment
The medicinal chemistry route to MK-5172 is based on a ring-closing metathesis strategy (S. Harper et al.ACS Med. Chem. Lett. 2012, 3, 332). The best regioselectivity (20:1) and minimization of double substitution in the SNAr reaction of A with B was achieved using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the base in polar solvents such as DMSO, NMP, or DMAc.
A new take on efficient delivery in regenerative medicine
http://www.newsfix.ca/2013/11/13/new-take-efficient-delivery-regenerative-medicine/
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MACITENTAN, Actelions, pulmonary arterial hypertension investigational drug
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MACITENTAN
N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N’-propylsulfamide,
N-[5-(4-Bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl] -N’-propylsulfamide
CAS NO 441798-33-0
ACT-064992, Opsumit,UNII-Z9K9Y9WMVL
Mechanism of Action: Endothelin receptor antagonist (ERA)
Date of Approval: October 18, 2013(US)
Indication: Pulmonary Hypertension (PAH)
Company: Actelion Pharmaceuticals Ltd
PCT patent application: WO2002053557
FDA N204410, MACITENTANTABLET; ORAL10MG, OPSUMIT, ACTELION PHARMS LTD
Macitentan is achiral
Macitentan is a crystalline powder that is insoluble in water. In the solid state macitentan is very stable, is not hygroscopic, and is not light sensitive.
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DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO
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