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DRUG SPOTLIGHT…LEVETIRACETAM « New Drug Approvals

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Star fruit neurotoxin identified, Caramboxin

Star fruit neurotoxin identified

Neurotoxin from Star Fruit

Patients with kidney disease have to watch what they eat: bananas, oranges, tomatoes, nuts, broccoli, and beans are all off-limits. Putting star fruit or carambola on the menu would be downright dangerous. This fruit contains a substance that is a deadly neurotoxin for people with kidney disease. Brazilian researchers have now isolated and identified this neurotoxin. As they report in the journal Angewandte Chemie, it is an amino acid similar to phenylalanine.

Caramboxin: Patients suffering from chronic kidney disease are frequently intoxicated after ingesting star fruit. The main symptoms of this intoxication are named in the picture. Bioguided chemical procedures resulted in the discovery of caramboxin, which is a new phenylalanine-like molecule that is responsible for intoxication. Functional experiments in vivo and in vitro point towards the glutamatergic ionotropic molecular actions of caramboxin, which explains its convulsant and neurodegenerative properties.

Read more

Sweet Poison

http://www.chemistryviews.org/details/ezine/5542471/Sweet_Poison.html

star fruit (Averrhoa carambola) or carambola has been cultivated in Malaysia, Southern China, Taiwan, India and Brazil. It is rather popular in the Philippines and Queensland, Australia and moderately so in some of the South Pacific Islands, particularly Tahiti, New Caledonia and Netherlands New Guinea, Guam and in Hawaii and south Florida. There are some subspecies in the Caribbean Islands, in Central America and in tropical West Africa. The fruits are also available in many European countries and Canada. Range of soluble oxalate salts concentrations obtained from many cultivars varies from 80 to 730 mg/100 g of the fruit

Structural Elucidation and Spectroscopic Data of Caramboxin (1)
Most 1H and 13C NMR data from the isolated compound were easily assigned due to the relationship
of this compound with well-known aromatic amino acids such as phenylalanine. The side chain is
identical to phenylalanine as attributed in the NMR data below. The tetra-substituted pattern of the aromatic ring was also easily recognized by the only two signals for aromatic protons at δ 6.42 and6.37 with a coupling constant (2.0 Hz) typical of aromatic meta coupling. The positioning of
substituents in the aromatic ring were attributed due to the 13C chemical shifts and confirmed by
HMBC experiment. In this way acetyl group was placed at C-6 due to the low chemical shift (104.1ppm) of this aromatic carbon; methoxyl was placed at C-3 due to its highest chemical shift (165.2ppm) among aromatic protons, which was confirmed by HMBC experiment; finally the hydroxyl group was placed at the remaining C-5. Comparison of the observed accurate mass measurement with theoretically calculated formulae for the signal at m/z 256.0823 allows only a few reasonable [MH]+ ion formulae within a standard deviation of 50 ppm. The ion formula [C11H13NO6 + H]+ had the best mass accuracy (0.7 ppm error) and correlation with the NMR spectra. The MS/MS spectrum of m/z 256 shows an intense ion at m/z 192 in addition to neutral elimination of H2O (m/z 238) and CO2 (m/z 212) from the carboxylic acid group. In source dissociation followed by MS/MS analysis revealed that m/z 192 was only obtained from m/z 238, due to the elimination of CH2O2 (46 massunits) as a neutral molecule by 1,2 elimination. The same mechanism was also observed for the m/z166 formation from the ion at m/z 212. Finally, 2D NMR data from HMQC and HMBC confirmed the entire spectral assignment

Caramboxin: 1H-NMR (400 MHz, D2O) δ 6.42 (d, J = 2.0 Hz, 1H, H-4), 6.37 (d, J = 2.0 Hz, 1H, H-2), 4.25 (dd, J = 5.5, 8.0 Hz, 1H, H-8), 3.80 (s, 3H, H-11), 3.66 (dd, J = 14.0, 5.5 Hz, 1H, H-7A),3.18 (dd, J = 14.0, 8.0 Hz, 1H, H-7B);

13C-NMR (100 MHz, DMSO-d6) δ 172.8 (C, C-9), 171.2 (C,C-10), 165.2 (C, C-5), 162.2 (C, C-3), 138.8 (C, C-1), 110.0 (CH, C-2), 104.1 (C, C-6), 100.5 (CH,C-4), 55.4 (CH3, C-11), 53.5 (CH, C-8), 35.9 (CH2, C-7); 15N-NMR (50 MHz, DMSO-d6) δ -268(nitromethane as internal reference).

HMBC (500 MHz, DMSO-d6): H-2 → C-3, C-4, C-7; H-4 →C-2, C-3, C-5; H-7 → C-1, C-2, C-8, C-9; H-8 → C-1, C-7, C-9; H-11 → C-3;

HRMS (m/z): [MH]+calcd for C11H14NO6, 256.0816; found: 256.0818

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SHIMOGA,  KARNATAKA, INDIA

Shimoga - Wikipedia, the free encyclopedia

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Shimoga, officially renamed as Shivamogga, is a city and the district headquarters of Shimoga District in the central part of the state of Karnataka, India. The city ...

‎Shimoga district - ‎Shimoga Airport - ‎Category:Shimoga

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Shimoga–Talaguppa railway

Kundadri, Shimoga

Shimoga Photos - Kudli Temple






Ornate baluster in Thripuranthakeshwara temple at Balligavi, Shimoga district.jpg



sigandur - Shimoga

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Aripiprazole spectral data

Aripiprazole

A mixture of 7-(4-Bromobutoxy)-2(1H)-quinolinone (297 g, 1.0 mol), NaI (234 g, 1.56 mol),
triethylamine (173.7 g, 1.72 mol) and 1-(2, 3-dichlorophenyl)-piperazine hydrochloride (381
g, 1.43 mol), in acetonitrile (750 mL) was refluxed for 4 h with stirring. Progress of reaction
was monitored by TLC; using benzene: ethyl acetate (7:3) solvent system. The reaction
mixture was filtered, and the filtrate was evaporated to dryness in vacuo. The residue was
extracted with CHCl3, and the extract was washed, dried, and evaporated in vacuo.
Recrystallization from MeOH-CHCl3 gave the desired product as colorless needles. Product
Yield: 407.0 g, 84 %

http://jocpr.com/vol2-iss5-2010/JCPR-2010-2-5-506-517.pdf



IR
3368 (N-H stretching),
3109 (aromatic C-H stretching),
2944(aliphatic C-H stretching),
1677 (C=O stretching),
1594-1445(aromatic region),
1174 (C-N stretching),
779 (C-Cl stretching).

NMR
ð 1.77-1.72 ppm (t, 2H, -CH2),
1.83-1.79 (t, 2H, -CH2),
2.50-2.45(t, 2H, -CH2),
2.63-2.58 (m, 6H, CO-CH2-CH2 of carbostyryl,CH2 of piperazine),
2.91-2.86 (m, 2H, -CH2 of piperazine),
3.06(s, 4H, -CH2 of piperazine),
6.30-6.29 (s, 1H, -ArH),
6.53-6.50 (dof d, 1H,-ArH),
6.98-6.93 (m, 1H, -ArH),
7.05-7.02 (d, 1H, -ArH),
7.16-7.10 (d, 2H, -ArH),
7.79 (s, 1H, -NH)






1H NMR spectrum of Aripiprazole (CDCl3, 298 K, 600 MHz): 8.52 (s,1H),
7.14-7.15 (m,2H), 7.04 (d,1H,J=8.30 Hz), 6.96 (dd,1H,J=7.10,2.52Hz), 6.52
(dd,1H,J=8.30,2.30 Hz), 6.36 (d,1H,J=2.30 Hz), 3.96 (t,2H,J=6.25 Hz), 3.07 (m,4H), 2.89
(t,2H,J=7.50 Hz), 2.65 (m,4H), 2.62 (t,2H,J=7.50 Hz), 2.48 (t,2H,J=7.55 Hz), 1.82
(m,2H), 1.71 (m,2H).

1H-NMR spectral data of Aripiprazole (DMSO-d6, 298 K, 600 MHz): 9.98 

(s,1H), 7.28-7.30 (m,2H), 7.12 (dd,1H,J=7.10,2.35 Hz), 7.04 (d,1H,J=8.30 Hz), 6.48 

(dd,1H,J=8.30,2.35 Hz), 6.45 (d,1H,J=2.35 Hz), 3.96 (t,2H,J=6.45 Hz), 2.97 (m,4H), 2.78 

(t,2H,J=7.45 Hz), 2.52 (m,4H), 2.41 (t,2H,J=7.45 Hz), 2.38 (t,2H,J=7.15 Hz), 1.72 

(m,2H), 1.58 (m,2H)

1H NMR spectrum of Aripiprazole (CD3OH, 298 K, 500 MHz): 9.80 (bs,1H), 

7.18-7.24 (m,2H), 7.02-7.09 (m,2H), 6.54 (dd,1H,J=8.25,2.45 Hz), 6.44 (d,1H,J=2.49 

Hz), 3.97 (t,2H,J=6.15 Hz), 3.06 (m,4H), 2.85 (t,2H,J=7.35 Hz), 2.67 (m,4H), 2.47-2.54 

(m,4H), 1.79 (m,2H), 1.73 (m,2H). 

1. Sixth polymorph of Aripiprazole - an antipsychotic drug.

   www.rsc.org/suppdata/ce/c2/c2ce25306b/c2ce25306b.pdf‎
   

   
   

   H NMR spectrum of Aripiprazole (CDCl3, 298 K, 600 MHz): 8.52 (s,1H),. 7.14-7.15 (m,2H), 7.04 (d,1H,J=8.30 Hz), 6.96 (dd,1H,J=7.10,2.52Hz), 6.52. (dd,1H ...
   
   
   

   Spectroscopic studies of aripiprazoleDownload the full text		Download the full text
   Author:	Li Jianfeng 1, Liu Aixiang 1, Xia Guang-xin 1, 2, was also abundant, Shen Jing Shan 1 *
   Journal Name:	Spectroscopy and Spectral Analysis
   Title:	200 727 (05)
   Post time:	2006.12.18
   Download URL:	www.gpxygpfx.com/qikan/manage/wenzhang/2007-05-0863.pdf

   
   http://www.gpxygpfx.com/qikan/manage/wenzhang/2007-05-0863.pdf

Aripiprazole (7-[4-[4- (2,3-dichlorophenyl) piperazin-1-yl] butoxy]-3,4- dihydro- 1H quinolin-2-one) is an anti - psychotic drug.

US20120316180

https://www.google.com/patents/US20120316180

¹H-NMR spectrum (DMSO-d₆, TMS) shown in FIG. 23. Specifically, it has characteristic peaks at 1.55-1.63 ppm (m, 2H), 1.68-1.78 ppm (m, 2H), 2.35-2.46 ppm (m, 4H), 2.48-2.56 ppm (m, 4H 4-DMSO), 2.78 ppm (t, J=7, 4 Hz, 2H), 2.97 ppm (brt, J=4.6 Hz, 4H), 3.92 ppm (t, J=6.3 Hz, 2H), 6.43 ppm (d, J=2.4 Hz, 1H), 6.49 ppm (dd, J=8.4 Hz, J=2.4 Hz, 1H), 7.04 ppm (d, J=8.1 Hz, 1H), 7.11-7.17 ppm (m, 1H), 7.28-7.32 ppm (m, 2H) and 10.00 ppm (s, 1H);


 IR (KBr) spectrum shown in FIG. 21. Specifically, it has clear infrared absorption bands at 2943, 2817, 1686, 1377, 1202, 969 and 774 cm⁻¹.

Aripiprazole methanol solvate

HPLC purity: 99.39%, Methanol content: 6.57% Elemental analysis: C: 59.88%, H: 6.60%, N: 8.62% and calculated values for C₂IH₃ICl₂N₃O₃. C: 59.95%, H: 6.45%, N: 8.74%

IR Spectrum (KBr, cm-¹): 3196, 3108, 2948, 2819, 1675, 1628, 1595, 1578, 1522, 1449, 1378, 1335, 1274, 1243, 1197, 1173, 1140, 1127, 1040, 997, 960, 859, 830, 809, 784, 748, 713 and 532.

¹H NMR (300 MHz, CDCl₃, ppm) : 1.65 - 1.85 («ι, 4H), 2.49 (t, 2H), 2.51 (t, 2H), 2.59 - 2.64 (m, 4H), 2.89 (t, 2H), 3.08 (m, 4H), 3.49 (s, 3H),

3.97 (t, 2H), 6.32 (d, IH), 6.51- 6.54 (dd, IH), 6.94 - 6.97 (m, IH), 7.05 (d, IH), 7.11 - 7.17 (m, 2H), 8.04 (s, IH).

¹³C NMR (300 MHz, DMSO-d₆, ppm): 23.19, 24.38, 27.14, 30.90, 50.17, 51.08, 53.12, 58.07, 67.7, 102.2, 108.7, 115.5, 118.5, 124.39, 127.31, 127.34, 128.4, 133.8, 138.1, 151.1, 158.5 and 172.41.

Mass Spectrum (M+): 448.2, 285.1/ 218.1, 176.0, and 164.1. The XRD shows the peaks at 9.4, 10.7, 11.4, 11.8, 12.3, 13.3, 17.3, 18.4, 19.8, 23.3, 24.3, 25.6, 26.8, 28.0, 28.9, 31.2° + 0.2 2 theta values

(R)-2-(2-hydroxy-1-phenylethyl)isoindoline-1,3-dione

Equimolar ratios of both heated at 145 deg c for 4 hrs and then the oil  titurated in DCM , Dried over sodium sulphate , evapn gives oil , used as such for next step. is a method of protection of amino gp

 2-[(1R)-2-Hydroxy-1-phenylethyl]-1H-isoindole-1,3(2H)-dione

205380-30-9  cas no

SpectralData

¹H NMR (400 MHz, 298 K, CDCl₃) δ_H 7.83 – 7.74 (2H, m, Pht), 7.70 – 7.60 (2H, m, Pht), 7.49 (2H, d, ³J_HH = 7.4 Hz, Ph), 7.41 – 7.23 (3H, m, Ph), 

5.51 (1H, dd, ³J_HH = 8.9 Hz, ³J_HH = 5.0 Hz, CH), 

4.76 – 4.66 (1H, m, CH₂), 

4.24 (1H, dd, ³J_HH = 11.4 Hz, ⁴J_HH = 4.9 Hz, CH₂), 

3.47 (1H, s, OH).

¹³C NMR (100 MHz, 298 K, CDCl₃) δ_C 168.89 (C=O), 

136.88, 134.08 (Pht), 131.72, 128.70, 128.13, 127.97 (Ph), 123.31 (Pht), 

61.98 (CH₂), 57.46 (CH).

MS (ESI⁺) m/z 290.1 ([M+Na]⁺)

IR (cm^-1) ν 3457, 1772, 1700, 1611, 1585, 1495, 1467, 1388, 1358, 1332, 1288, 1266, 1185, 1172, 1120, 1065, 1040, 1013, 999, 962, 919, 877, 838, 793, 765, 719, 698.

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M. D. Chen, M. Z. He, X. Zhou, L. Q. Huang, Y. P. Ruan and P. Q. Huang, Tetrahedron, 2005, 61, 1335-1344http://dx.doi.org/10.1016/j.tet.2004.10.109

 http://www.sciencedirect.com/science/article/pii/S0040402004019143

Aguilar, Nuria; Moyano, Albert; Pericas, Miquel A.; Riera, Antoni 
Synthesis, 1998 ,  3,   p. 313 - 316

Late-stage success for Sanofi/Regeneron RA drug sarilumab « New Drug Approvals

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2,2,2-Trifluoro-1-(4-methoxyphenyl)ethanol

2,2,2-Trifluoro-1-(4-methoxyphenyl)ethanol

 

2,2,2-trifluoro-1-(4-methoxyphenyl)-ethanol 2,2,2-trifluor-1-(4-methoxyphenyl)ethanol 2,2,2-trifluoro-1-(4-méthoxyphényl)éthanol 2,2,2-トリフルオロ-1-(4-メトキシフェニル)エタノール
Physical Properties
Melting Point: n/a Boiling Point: 87-88 ºC (1 mmHg) Density: n/a Refractive Index: n/a
H1 NMR Spectrum:	Predict NMR spectrum

 

Data

1H NMR (CDCl₃, 400 MHz) d ppm 3.24 - 3.37 (m, 1 H)
3.80 (s, 3 H) O-CH3
4.91 (q, J=6.85 Hz, 1 H) C-H
6.92 (d, J=8.80 Hz, 2 H) arom-H ortho to oxygen
7.37 (d, J=8.80 Hz, 2 H) arom-H

 13C NMR (CDCl₃, 101 MHz) d ppm
55.51 (CH₃) O-CH3
72.60 (q, J_C-C-F = 31.50 Hz, CH) CH-(OH)-CF3
114.28 (CH) AROM-C
120.44 – 128.84 (q, J_C-F = 281.70 Hz, CF₃)
126.54 (d, J_C-C-C-F = 1.47 Hz, CH) CARBON ATOM ON AROM RING ATTACHED TO -CH-(OH)-CF3
129.07 (C) AROM-C META TO OXYGEN ATOM
160.60 (C) AROM C-O-CH3

 19F NMR (CDCl₃, 377 MHz) d ppm -78.61 (d, J = 6.81 Hz) 

GC-MS (EI) 206 ([M]+, 37%), 137 (100%), 109 (27%), 94 (28%), 77 (25%), 69 (4%).

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Kelly, C. B.; Colthart, A. M.; Constant, B.D.; Corning, S.R.; Dubois, L. N. E.;  Genovese, J. T.; Radziewicz, J. L.; Sletten, E. M.; Whitaker, K. R.; Tilley, J. J. Org. Lett.2011, 13, 1646.

Krishnamurti, R.; Bellew, D. R.; Prakash, G. K. S.  J.  Org. Chem. 1991, 56, 984.
DOI: 10.1021/jo00001a002