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Plus the 14 other new drugs marketed in 2010.
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DR ANTHONY MELVIN CRASTO Ph.D ( ICT, Mumbai)
, INDIA
36Yrs Exp. in the feld of Organic Chemistry,Working for AFRICURE PHARMA as ADVISOR earlier with GLENMARK PHARMA at Navi Mumbai, INDIA. Serving chemists around the world. Helping them with websites on Chemistry.Million hits on google,
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Ledipasvir (formerly GS-5885), Treatment of chronic Hepatitis C infection
Ledipasvir (formerly GS-5885), Treatment of chronic Hepatitis C infection
Ledipasvir nonproprietary drug name
http://www.ama-assn.org/resources/doc/usan/ledipasvir.pdf
November 28, 2012. N12/139. STATEMENT ON A NONPROPRIETARY NAME ADOPTED BY THE USAN COUNCIL. USAN ZZ-132. LEDIPASVIR.
MOLECULAR FORMULA C49H54F2N8O6
MOLECULAR WEIGHT 889
Gilead Sciences
CODE DESIGNATION GS-5885
CAS REGISTRY NUMBER 1256388-51-8
Ledipasvir (formerly GS-5885) is an experimental drug for the treatment of hepatitis C being developed by Gilead Sciences.[1] It is currently in Phase III clinical trials.[2] It is being studied in combination with other direct-acting antiviral agents that interfere with HCV replication.
Ledipasvir is an inhibitor of the hepatitis C virus HCV NS5A protein.
Ledipasvir is being tested in interferon-free regimens with other direct-acting antiviral agents for hepatitis C.
Data presented at the 20th Conference on Retroviruses and Opportunistic Infections in March 2013 showed that a triple regimen of the HCV protease inhibitor sofosbuvir, ledipasvir, and ribavirin produced a 12-week post-treatment sustained virological response (SVR12) rate of 100% for both treatment-naive patients and prior non-responders with HCV genotype 1.[3][4] Gilead is developing a sofosbuvir + ledipasvir coformulation that is being tested with and without ribavirin.
- “Ledipasvir”. United States Adopted Name.
- “GS-5885”. Gilead Sciences.
- ELECTRON: 100% Suppression of Viral Load through 4 Weeks’ Post-treatment for Sofosbuvir + Ledipasvir (GS-5885) + Ribavirin for 12 Weeks in Treatment-naïve and -experienced Hepatitis C Virus GT 1 Patients. Gane, Edward et al. 20th Conference on Retroviruses and Opportunistic Infections. March 3–6, 2013. Abstract 41LB.
- CROI 2013: Sofosbuvir + Ledipasvir + Ribavirin Combo for HCV Produces 100% Sustained Response. Highleyman, Liz. HIVandHepatitis.com. 4 March 2013.
Cempra Provides Guidance on the Clinical Program Required for Regulatory Approval for Solithromycin for Community-Acquired Bacterial Pneumonia (CABP)
solithromycin
(3aS,4R,7S,9R,10R,11R,13R,15R,15aR)-1-[4-[4-(3-aminophenyl)-1H-1,2,3-triazol-1-yl]butyl]-4-ethyl-7-fluorooctahydro-11-methoxy-3a,7,9,11,13,15-hexamethyl-10-{[3,4,6-trideoxy-3-(dimethylamino)-β-D–xylo-hexopyranosyl]oxy}-2H-Oxacyclotetradecino[4,3-d]oxazole-2,6,8,14(1H,7H,9H)-tetrone
| Legal status | Phase III clinical trials, North America, South America, Europe |
|---|---|
| Routes | oral, intravenous |
| Identifiers | |
| CAS number | 760981-83-7 |
Cempra Provides Guidance on the Clinical Program Required for Regulatory …
The Herald | HeraldOnline.com
The Phase 3 solithromycin clinical program in CABP will be planned to consist of an oral trial and an intravenous (IV)-to-oral clinical trial. Cempra followed the CABP guidance that the FDA proposed in a November, 2011, meeting of the Anti-Infective …
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http://www.heraldonline.com/2013/06/13/4944834/cempra-provides-guidance-on-the.html
Solithromycin (formerly known as CEM-101 and OP-1068) is a novel ketolide antibiotic undergoing clinical development for the treatment of community-acquired pneumonia (CAP) and other infections.It is expected to be the first macrolide antibiotic available in intravenous, oral, and pediatric suspension formulations in over 20 years.
Solithromycin exhibits excellent in vitro activity against a broad spectrum of Gram-positive respiratory tract pathogens, including macrolide-resistant strains. Solithromycin has activity against a wide variety of pathogens, and further research is being conducted for other infections.
- May 2011: Solithromycin is in a Phase 2 clinical trial for serious community-acquired bacterial pneumonia (CABP) and in a Phase 1 clinical trial with an intravenous formulation.
- September 2011 : Encouraging results from the phase 2 clinical trial versus levofloxacin were reported.
FDA Approves Xgeva,denosumab to Treat Giant Cell Tumor of the Bone
June 13, 2013 — The U.S. Food and Drug Administration today expanded the approved use of Xgeva (denosumab) to treat adults and some adolescents with giant cell tumor of the bone (GCTB), a rare and usually non-cancerous tumor.
GCTB generally occurs in adults between the ages of 20 and 40 years. In most cases, GCTB does not spread to other parts of the body but destroys normal bone as it grows, causing pain, limited range of motion and bone fractures. Rarely, GCTB can transform into a cancerous tumor and spread to the lungs.
Xgeva is a monoclonal antibody that binds to RANKL, a protein essential for maintenance of healthy bone. RANKL is also present in GCTB. Xgeva is intended for patients whose GCTB cannot be surgically removed (unresectable) or when surgery is likely to result in severe morbidity, such as loss of limbs or joint removal. It should only be used in adolescents whose bones have matured
http://www.drugs.com/newdrugs/fda-approves-xgeva-giant-cell-tumor-bone-3815.html
Denosumab is a fully human monoclonal antibody for the treatment of osteoporosis, treatment-induced bone loss, bone metastases, rheumatoid arthritis, multiple myeloma, and giant cell tumor of bone. It was developed by the biotechnology companyAmgen.
Denosumab is designed to inhibit RANKL (RANK ligand), a protein that acts as the primary signal for bone removal. In many bone loss conditions, RANKL overwhelms the body’s natural defenses against bone destruction.
In June 2010, denosumab was approved by the U.S. Food and Drug Administration (FDA) for use in postmenopausal women with risk of osteoporosis under the trade nameProlia, and in November 2010, as Xgeva, for the prevention of skeleton-related events in patients with bone metastases from solid tumors.Denosumab is the first RANKL inhibitor to be approved by the FDA. In the summer of 2011 clinical trials were investigating denosumab in giant cell tumors, multiple myeloma with bone metastases, and hypercalcemia of malignancy, and further investigating its dosing and safety.
Synthetic approaches to the 2011 new drugs-Bioorganic & Medicinal Chemistry Vol 21, (11), 2013, Pg 2795–2825
Volume 21, Issue 11, 1 June 2013, Pages 2795–2825
Synthetic approaches to the 2011 new drugs
- a Shenogen Pharma Group, Beijing, China
- b Pfizer Inc., San Diego, CA 92121, USA
- c Pfizer Inc., Groton, CT 06340, USA
- http://dx.doi.org/10.1016/j.bmc.2013.02.061,http://www.sciencedirect.com/science/article/pii/S0968089613002642
Abstract
New drugs are introduced to the market every year and each represents a privileged structure for its biological target. These new chemical entities (NCEs) provide insights into molecular recognition and also serve as leads for designing future new drugs. This review covers the synthesis of 26 NCEs that were launched in the world in 2011.
Synthetic approaches to the 2010 new drugs-Review Article Bioorganic & Medicinal Chemistry, Vol 20, Issue 3,2012, Pg 1155-1174
| Synthetic approaches to the 2010 new drugsReview Article Bioorganic & Medicinal Chemistry, Volume 20, Issue 3, 1 February 2012, Pages 1155-1174 Kevin K.-C. Liu, Subas M. Sakya, Christopher J. O’Donnell, Andrew C. Flick, Hong X. Ding |
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Amgen’s Experimental Ovarian Cancer Drug, Trebananib, Shows Positive Results In Late Stage Clinical Trials
STRUCTURAL FORMULA ,Trebananib, AMG-386
Monomer
MDKTHTCPPC PAPELLGGPS VFLFPPKPKD TLMISRTPEV TCVVVDVSHE 50
DPEVKFNWYV DGVEVHNAKT KPREEQYNST YRVVSVLTVL HQDWLNGKEY 100
KCKVSNKALP APIEKTISKA KGQPREPQVY TLPPSRDELT KNQVSLTCLV 150
KGFYPSDIAV EWESNGQPEN NYKTTPPVLD SDGSFFLYSK LTVDKSRWQQ 200
GNVFSCSVMH EALHNHYTQK SLSLSPGKGG GGGAQQEECE WDPWTCEHMG 250
SGSATGGSGS TASSGSGSAT HQEECEWDPW TCEHMLE 287
Disulfide bridges location
7-7′ 10-10′ 42-102 42′-102′ 148-206
148′-206′ 239-246 239′-246′ 275-282 275′-282′
CAS REGISTRY NUMBER 894356-79-7
MOLECULAR FORMULA C2794H4248N752O886S30
Trebananib
Immunoglobulin G1 (synthetic human Fc domain fragment) fusion protein with
angiopoietin 1/angiopoietin 2-binding peptide (synthetic)
http://www.ama-assn.org/resources/doc/usan/trebananib.pdf
http://www.genome.jp/dbget-bin/www_bget?dr:D10177
Amgen’s Experimental Ovarian Cancer Drug, Trebananib, Shows Positive …
Medical Daily
Amgen, a large biotechnology company out of Thousand Oaks, Calif. has announced that its drug for reoccurring ovarian cancer has shown positive results in Phase III clinical trials. The trials sought to stop the progression of ovarian cancer and extend …
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Miglustat- to treat Type 1 Gaucher disease (GD1)
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| Miglustat | |
| (2R,3R,4R,5S)-1-butyl-2-(hydroxymethyl)piperidine-3,4,5-triol |
PATENT-US 5,525,616, US 5,472,969 TO Actelion Pharms Ltd
Miglustat is a drug developed by Actelion and is used primarily to treat Type 1 Gaucher disease (GD1). It is marketed under the trade name Zavesca. Miglustat (OGT 918, N-butyl-deoxynojirimycin) is an imino sugar (molecular weight: 219 daltons), a synthetic analogue of D-glucose and a white to off-white crystalline solid that has a bitter taste The primary pharmacological activity of miglustat is inhibition of the enzyme glucosylceramide synthase, catalyzing the first step in the biosynthesis of glycosphingolipids (GSL), i.e., the formation of glucosylceramide (GlcCer). Reduced formation of GlcCer will lead to decreased biosynthesis of more complex GSL. This therapeutic principle, called substrate reduction therapy (SRT), may be useful in disorders of intracellular (predominantly lysosomal) accumulation of GSL either due to their deficient breakdown or intracellular transport/trafficking. Miglustat exhibits a large volume of distribution and has the capacity to access deep organs such as the brain, bone and lung.
Miglustat is a synthetic derivative of a family of polyhydroxylated alkaloids or amino sugar extracted from plants and microorganisms. Its synthesis starts from D-glucose sugar in plants. The sugar then aminated and oxidized to amino fructose sugar, which then can form a cyclic aminohemiacetal called nojirimycin. Then the dehydration and reduction takes place successively before the formation of deoxynojirimycin, which is a precursor of miglustat. Since it is a synthetic derivative drug, alkylation ofdeoxynojirimycin can be synthesized in the laboratory with 1-butyl halide via amine alkylation.
Miglustat
CAS : 72599-27-0
(2R,3R,4R,5S)-1-Butyl-2-(hydroxymethyl)-3,4,5-piperidinetriol
Additional Names: N-butyldeoxynojirimycin; N-butylmoranoline
Manufacturers’ Codes: OGT-918; SC-48334
Trademarks: Zavesca (Actelion)
Molecular Formula: C10H21NO4
Molecular Weight: 219.28
C 54.77%, H 9.65%, N 6.39%, O 29.19%
Literature Ref: Amino sugar; inhibitor of glucosyltransferase, an enzyme involved in the biosynthesis of glycosphingolipids.
Prepn: B. Junge et al., DE 2758025; see also, eidem, US 4639436 (1979, 1987 both to Bayer).
Improved synthesis: E. W. Baxter, A. B. Reitz, J. Org. Chem. 59, 3175 (1994); C. R. R. Matos et al., Synthesis 1999, 571.
In vitro efficacy vs HIV: A. Karpas et al., Proc. Natl. Acad. Sci. USA 85, 9229 (1988). Inhibition of glycolipid biosynthesis: F. M. Platt et al., J. Biol. Chem. 269, 8362 (1994).
Clinical evaluation in Gaucher’s disease: T. Cox et al., Lancet 355, 1481 (2000). Review of pharmacology and clinical development in Gaucher’s disease: P. L. McCormack, K. L. Goa, Drugs 63, 2427-2434 (2003).
Properties: White to off-white crystalline solid, mp 125-126°. [a]D25 -15.9° (c = 0.77 in water). Highly sol in water (>1000 mg/ml).
Melting point: mp 125-126°
Optical Rotation: [a]D25 -15.9° (c = 0.77 in water)
Therap-Cat: In treatment of inherited glycosphingolipid lysosomal storage disorders.
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WORLD DRUG TRACKER
Capecitabine– treatment of metastatic breast and colorectal cancers.
Capecitabine, pentyl [1-(3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1H-pyrimidin-4-yl]carbamate
Capecitabine (Xeloda, Roche) is an orally-administered chemotherapeutic agent used in the treatment of metastatic breast and colorectal cancers. Capecitabine is a prodrug, that is enzymatically converted to 5-fluorouracil in the tumor, where it inhibits DNA synthesis and slows growth of tumor tissue.The activation of capecitabine follows a pathway with three enzymatic steps and two intermediary metabolites, 5′-deoxy-5-fluorocytidine (5′-DFCR) and 5′-deoxy-5-fluorouridine (5′-DFUR), to form 5-fluorouracil
Capecitabine is a chemotherapy drug that is administered as a treatment for a variety of cancer types, including bowel cancer, stomach cancer, breast cancer and oesophageal cancer. It acts as a prodrug, undergoing a three-step enzymic conversion into 5-fluorouracil in the tumour, where it inhibits DNA synthesis and thus slows growth of tumour tissue. Capecitabine can be synthesized from the readily available starting materials D-ribofuranose and cytosine [1].
When capecitabine is used for long-term treatment of recurrent cancers, one of the side-effects can be the onset of hand-foot syndrome, which eventually can lead to total eradication of the patients fingerprints [2]. This has recently proved rather inconvenient for one unsuspecting patient. A recent report [3] describes an instance where a patient on capecitabine for over three years went to the USA to visit relatives in December 2008. He was detained for 4 hours as his fingerprints could not be detected by immigration officials and was only allowed to enter after the officers were entirely satisfied that he posed no threat to security. As a result, all patients taking capecitabine long-term are being advised to travel with a letter from an oncologist stating condition and treatment being received to account for their lack of fingerprints.
As a final aside, recent reports suggest that the actual purpose of fingerprints is to enhance sensitivity rather than friction.
References
- Moon, B.S., Shim, A.Y., Lee, K.C., Lee, H.J., Lee, B.S., An, G.I., Yang, S. D., Chi, D.Y., Choi, C.W., Lim, S.M. and Chun, K.S. (2005) Synthesis of F-18 labeled capecitabine using [18F]F2 gas as a tumor imaging agent. Bull. Korean Chem. Soc. 26, 1865–1868.
- Chua, D., Wei, W.I., Sham, J.S.T. and Au, G.K.H. (2008) Capecitabine monotherapy for recurrent and metastatic nasopharyngeal cancer.Jpn. J. Clin. Oncol. 38, 244–249.
- Wong, M., Choo, S.-P. and Tan, E.-H. (2009) Travel warning with capecitabine. Annals of Oncology Advance Access May 26th 2009/doi:10.1093/annonc/mdp278.
http://promontory-science-education.webnode.com/animations/#.UbkbNtiNCS0
is link to below animation
AstraZeneca buys Pearl Therapeutics in $1.15bn deal
The UK’s second largest drug company, AstraZeneca, has announced that it will buy US-based lung disease drug specialist Pearl Therapeutics in a deal worth up to $1.15bn (£742m).
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DR ANTHONY MELVIN CRASTO
ORGANIC SPECTROSCOPY
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