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DR ANTHONY MELVIN CRASTO, WORLDDRUGTRACKER

Buthionine Sulphoximine

 Uncategorized  Comments Off on Buthionine Sulphoximine
May 112016
 

Skeletal formula of buthionine sulfoximine

Buthionine Sulphoximine

NDA Filed in china

A gamma-glutamylcysteine synthetase inhibitor potentially for the treatment of solid tumors.

 NSC-326231; BSO

CAS No. 5072-26-4

BUTHIONINE SULFOXIMINE; DL-Buthionine-[S,R]-sulfoximine; 5072-26-4; Buthionine sulfoxamine; Buthionine-S,R-sulfoximine; Buthione sulfoximine;

Molecular Formula: C8H18N2O3S
Molecular Weight: 222.30512 g/mol

Buthionine sulfoximine (BSO) is a sulfoximine which reduces levels of glutathione and is being investigated as an adjunct withchemotherapy in the treatment of cancer.[1] The compound inhibits gamma-glutamylcysteine synthetase, the enzyme required in the first step of glutathione synthesis. Buthionine sulfoximine may also be used to increase the sensitivity of parasites to oxidativeantiparasitic drugs.[2]

Buthionine sulphoximine is an oncolytic agent in early clinical development at the National Cancer Institute (NCI) for the treatment of neuroblastoma in pediatric patients in combination with melphalan and bone marrow or peripheral stem cell transplantation.

DATA

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1H NMR

 

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13C NMR

 

Synthesis

Methionine and buthionine sulfoximines: Syntheses under mild and safe imidation/oxidation conditions
Advanced Synthesis&Catalysis (2014), 356, (10), 2209-2213

Abstract

Thumbnail image of graphical abstract

Methionine and buthionine sulfoximines (MSO and BSO) are non-natural amino acids known to inhibit the biosynthesis of glutathione (GSH). The current syntheses of these biologically active molecules involve harsh reaction conditions and the use of hazardous reagents for the sulfur imidation. Here, improved syntheses of MSO and BSO are presented including safe and mild one-pot imidation/oxidation sequences and single-step deprotections of three different functionalities.

Methionine and Buthionine Sulfoximines: Syntheses under Mild and Safe Imidation/Oxidation Conditions

  1. Laura Buglioni,
  2. Vincent Bizet and
  3. Carsten Bolm*

DOI: 10.1002/adsc.201400354

http://onlinelibrary.wiley.com/doi/10.1002/adsc.201400354/abstract

References

  1.  Defty, CL; Marsden, JR (2012). “Melphalan in regional chemotherapy for locally recurrent metastatic melanoma.”. Current topics in medicinal chemistry 12 (1): 53–60. PMID 22196271.
  2.  “Definition of buthionine sulfoximine – National Cancer Institute Drug Dictionary”.

BUTHIONINE SULFOXIMINE.png

Buthionine sulfoximine
Skeletal formula of buthionine sulfoximine
Ball-and-stick model of buthionine sulfoximine as a zwitterion
Names
IUPAC name

2-amino-4-(butylsulfonimidoyl)butanoic acid
Other names

BSO
Identifiers
5072-26-4 
ChEBI CHEBI:28714 Yes
ChemSpider 19896 Yes
Jmol 3D model Interactive image
MeSH Buthionine+sulfoximine
PubChem 21157
Properties
C8H18N2O3S
Molar mass 222.305 g/mol
Density 1.29 g/mL
Melting point 215 °C (419 °F; 488 K)
Boiling point 382.3 °C (720.1 °F; 655.5 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

////NSC-326231,  BSO, 5072-26-4, Butionine sulfoximine, Neuroblastoma

CCCCS(=N)(=O)CCC(C(=O)O)N

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Multibiphenyl A, New biphenyls from Garcinia multiflora.

 Uncategorized  Comments Off on Multibiphenyl A, New biphenyls from Garcinia multiflora.
May 112016
 

Figure 2 Selected HMBC (H→C) and 1H-1H correlation spectroscopy (COSY) (–) correlations of 1. 

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Compound 1 was obtained as a pale yellow gum. The molecular formula was determined to be C20H22O6 from the molecular ion peak [M]+ at m/z 358.1408 in the EI-HRMS. The IR spectrum indicated that 1 possesses hydroxy (3422 cm-1), phenyl (2939, 1498 cm-1), and carbonyl (1721 cm-1) functional groups. The 1H and 13C NMR spectra (Table 1) revealed the signals for a 1,2,3,4,5-pentasubstituted benzene ring [dH 6.26 (1H, s, H-6); δC 129.6 (C-1), 119.7 (C-2), 144.9 (C-3), 135.0 (C-4), 147.2 (C-5), 105.9 (C-6)], one p-substituted benzene ring [dH 7.00 (2H, dd, J 8.8, 2.4 Hz, H-8, H-12), 6.74 (2H, dd, J 8.8, 2.4 Hz, H-9, H-11); δC 133.8 (C-7), 131.7 (C-8, C-12), 115.7 (C-9, C-11), 157.1 (C-10)], one acetoxyprenyl group [dH 3.21 (2H, d, J 6.7 Hz, H-1′), 5.44 (1H, d, J6.7 Hz, H-2′), 4.33 (2H, s, H-4′), 1.39 (3H, s, H-5′), and 1.99 (3H, s, H-OAc); δC 26.8 (C-1′), 130.7 (C-2′), 134.6 (C-3′), 71.5 (C-4′), 14.0 (C-5′), 172.9, 20.8 (OAc)], and one methoxy group [dH 3.76 (3H, s, OMe-5); δC 56.5 (OMe)], which implied that compound1 was a biphenyl derivative. This conclusion was confirmed by the heteronuclear multiple bond correlation (HMBC) correlations of H-6 with C-7, and of H-8 and H-12 with C-1 (Figure 2). HMBC correlations of H-1′ with C-1, C-2, and C-3, and of H-2′ with C-1 suggested the acetoxyprenyl group at C-2. The methoxy group was located at C-5 from the HMBC correlations of δH 3.76 (OMe) with C-5. Considering the signal for quarternary C-3, C-4, C-10 and the molecular formula of 1, three hydroxy groups were located at C-3, C-4, C-10, respectively. Thus, the structure of 1 was determined as shown (Figure 1), and named multibiphenyl A.

Figure 1 New biphenyls from Garcinia multiflora

Multibiphenyl A (1)

Pale yellow gum; [α]D –11.0 (c 0.07, MeOH); UV (MeOH) lmax / nm (log ε) 570 (2.16), 205 (4.71); IR (KBr) n / cm-1 3422, 2939, 1721, 1611, 1589, 1498, 1443, 1357, 1266, 1172, 1102, 1045, 1023, 838; 1H and 13C NMR data (400 and 100 MHz, CD3OD), see Table 1; ESI-MS (positive mode) m/z 381 [M + Na]+; EI-HRMS (M+) calcd.: 358.1416; found: 358.1408 (C20H22O6).

Table 1 1H and 13C NMR data for compounds 1-3 (d in ppm, 1 and 2 in CD3OD, 3 in CDC13, 100 and 400 MHz) 

No. 1 2 3
δC (m) / ppm δH (m, J , Hz) / ppm δC (m) / ppm δH (m, J , Hz) / ppm δC (m) / ppm δH (m, J , Hz) / ppm
1 129.6 s 132.4 s 132.3 s
2 119.7 s 114.2 s 112.4 s
3 144.9 s 142.0 s 141.5 s
4 135.0 s 131.9 s 132.7 s
5 147.2 s 149.6 s 144.8 s
6 105.9 d 6.26 (s, 1H ) 106.6 d 6.44 (s, 1H) 105.5 d 6.43 (s, 1H)
7 133.8 s 134.6 s 132.7 s
8 131.7 d 7.00 (dd, 1H, J 8.8 Hz, 2.4) 131.8 d 7.11 (dd, 1H, J 8.4 Hz, 1.9) 130.3 d 7.16 (d, 1H, J 8.6 Hz)
9 115.7 d 6.74 (dd, 1H, J 8.8 Hz, 2.4) 116.0 d 6.82 (dd, 1H, J 8.4 Hz, 1.9) 114.8 d 6.86 (d, 1H, J 8.6 Hz)
10 157.1 s 157.7 s 155.5 s
11 115.7 d 6.74 (dd, 1H, J 8.8 Hz, 2.4) 116.0 d 6.82 (dd, 1H, J 8.4 Hz, 1.9) 114.8 d 6.86 (d, 1H, J 8.6 Hz)
12 131.7 d 7.00 (dd, 1H, J 8.8 Hz, 2.4) 131.8 d 7.11 (dd, 1H, J 8.4 Hz, 1.9) 130.3 d 7.16 (d, 1H, J 8.6 Hz)
1′ 26.8 t 3.21 (d, 2H, J 6.7 Hz, CH2) 124.7 d 6.41 (d, 1H, J 10.1 Hz) 21.1 t 2.59 (t, 2H, J 6.6 Hz, CH2)
2′ 130.7 d 5.44 (t, 1H, J 6.7 Hz) 124.4 d 5.48 (d, 1H, J 10.1 Hz) 33.0 t 1.72 (t, 2H, J 6.6 Hz, CH2)
3′ 134.6 s 77.6 s 74.7 s
4′ 71.5 t 4.33 (s, 3H, CH3) 69.0 t 4.27 (d, 1H, J 11.5 Hz, CH2) 26.7 q 1.39 (s, 3H, CH3)
4.14 (d, 1H, J 11.5 Hz, CH2)
5′ 14.0 q 1.39 (s, 3H, CH3) 23.4 q 1.47 (s, 3H, CH3) 26.7 q 1.39 (s, 3H, CH3)
3-OMe 56.5 q 3.76 (s, 3H, OCH3) 56.5 q 3.85 (s, 3H, OCH3) 56.1 q 3.86 (s, 3H, OCH3)
5′- OAc 172.9 s 172.6 s
20.8 q 1.99 (s, 3H, COCH3) 20.7 q 2.00 (s, 3H, COCH3)

Journal of the Brazilian Chemical Society

On-line version ISSN 1678-4790

J. Braz. Chem. Soc. vol.27 no.1 São Paulo Jan. 2016

http://dx.doi.org/10.5935/0103-5053.20150235

ARTICLES

New Biphenyls from Garcinia multiflora

Xue-Mei Gaoa  b  , Bing-Kun Jia  b  , Yin-Ke Lia  c  , Yan-Qing Yea  , Zhi-Yong Jianga  , Hai-Ying Yanga  , Gang Dua  , Min Zhoua  , Xiao-Xia Pana  , Wen-Xing Liua  , Qiu-Fen Hua  * 

aKey Laboratory of Chemistry in Ethnic Medicinal Resources, State Ethnic Affairs Commission & Ministry of Education, Kunming, P. R. China

bJoint Research Centre for International Cross-Border Ethnic Regions Biomass Clean Utilization in Yunnan, Yunnan Minzu University, 650031 Kunming, P. R. China

cCollege of Resource and Environment, Yuxi Normal University, 653100 Yuxi, P. R. China

ABSTRACT

Three new biphenyls were isolated from Garcinia multiflora. The structures of these biphenyls were elucidated by spectroscopic methods, and their rotavirus activity was evaluated.

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532016000100010&lng=en&nrm=iso&tlng=en

Key words: Garcinia multiflora,  biphenyls,  anti-rotavirus activity

 

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Lupin to co-market Novartis’ asthma drug in India

 Uncategorized  Comments Off on Lupin to co-market Novartis’ asthma drug in India
May 112016
 

Lupin to co-market Novartis’ asthma drug in India

Business Standard

BS B2B Bureau  |  Mumbai April 12, 2016 Last Updated at 10:27 IST

Novartis Healthcare will continue to market Sequadra (indacaterol/glycopyrronium inhaler), while Lupin will promote the inhaler under the brand name Loftair in India

read original article at

http://www.business-standard.com/content/b2b-pharma/lupin-to-co-market-novartis-asthma-drug-in-india-116041200249_1.html

 

/////inhaler, Novartis Healthcare,  Sequadra, indacaterol, glycopyrronium inhaler,  Lupin,  inhaler,  brand name,  Loftair, India

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