April 2015 – All About Drugs

Myself recovering from leg swelling

Uncategorized 1 Response »

Apr 172015

DR ANTHONY CRASTO at Metro hospital Manpada Thane, India

13-16 Apr, 2015

I am back

ENJOY

TAKE A TOUR

FREE

FIJI ISLAND

SUVA

The Treasure Island Resort Lunch Tour is a great option for your next Fiji itinerary.

Tavarua Island Resort, Fiji

////////

Design and Synthesis of Pyridinylisoxazoles and Their Anticancer Activities

Uncategorized Comments Off

Apr 102015

YANG Hongliang, XU Guoxing, BAO Meiying, ZHANG Dapeng, LI Zhiwei, PEI Yazhong
Design and Synthesis of Pyridinylisoxazoles and Their Anticancer Activities

2014 Vol. 35 (12): 2584-2592 [Abstract] ( 781 ) [HTML 0KB] [PDF 2464KB] (116 )
doi: 10.7503/cjcu20140333

Chemical Journal of Chinese Universities 2014, Vol. 35 Issue (12): 2584-2592 DOI: 10.7503/cjcu20140333

Abstract Based on the X-ray co-crystal structures of reported allosteric kinase inhibitors bound to their corresponding protein kinases, a pharmacophore model was proposed. To examine the validity of this hypothesis, 21 new pyridinylisoxazole derivatives were designed and synthesized. Their structures were confirmed using 1H NMR, 13C NMR and MS data. Their inhibitory effects against human breast cancer cell(MCF-7) proliferation were evaluated. Preliminary results indicated that some of these pyridinylisoxazole derivatives possess potent anti-proliferative activities, with IC50 data in the micromolar range. The mechanism-of-action of these compounds is under investigation.

Cite this article:

Design and Synthesis of Pyridinylisoxazoles and Their Anticancer Activities

YANG Hongliang¹, XU Guoxing¹, BAO Meiying², ZHANG Dapeng¹, LI Zhiwei¹, PEI Yazhong¹

1. The Center for Combinatorial Chemistry and Drug Discovery, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China;
2. Changchun Discovery Sciences Co. Ltd., Changchun 130012, China

YANG Hongliang,XU Guoxing,BAO Meiying et al. Design and Synthesis of Pyridinylisoxazoles and Their Anticancer Activities[J]. Chemical Journal of Chinese Universities, 2014, 35(12): 2584-2592.

URL:

http://www.cjcu.jlu.edu.cn/EN/10.7503/cjcu20140333 OR http://www.cjcu.jlu.edu.cn/EN/Y2014/V35/I12/2584

Displaying image006.png

Displaying image007.png

Displaying image010.png

VENLAFAXINE PART 1/3

GENERIC Comments Off

Apr 102015

Venlafaxine

CAS : 93413-69-5

CAS Name: 1-[2-(Dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexanol

Additional Names: (±)-1-[a-[(dimethylamino)methyl]-p-methoxybenzyl]cyclohexanol; N,N-dimethyl-2-(1-hydroxycyclohexyl)-2-(4-methoxyphenyl)ethylamine; venlafexine

Molecular Formula: C17H27NO2

Molecular Weight: 277.40

Percent Composition: C 73.61%, H 9.81%, N 5.05%, O 11.54%

SEE

part 1………http://orgspectroscopyint.blogspot.in/2015/04/venlafaxine.html / http://newdrugapprovals.org/2015/04/09/venlafaxine-part-12/

part 2……..http://newdrugapprovals.org/2015/04/09/venlafaxine-22/

PART 3…..http://orgspectroscopyint.blogspot.in/2015/04/venlafaxine-part-33.html

Chemistry

The chemical structure of venlafaxine is designated (R/S)-1-[2-(dimethylamino)-1-(4 methoxyphenyl)ethyl] cyclohexanol hydrochloride or (±)-1-[a [a- (dimethylamino)methyl] p-methoxybenzyl] cyclohexanol hydrochloride, and it has the empirical formula of C₁₇H₂₇NO₂. It is a white to off-white crystalline solid. Venlafaxine is structurally and pharmacologically related to the atypical opioid analgesic tramadol, and more distantly to the newly released opioid tapentadol, but not to any of the conventional antidepressant drugs, including tricyclic antidepressants, SSRIs, MAOIs, or RIMAs.^[66]

Venlafaxine
Systematic (IUPAC) name


(RS)-1-[2-dimethylamino-1-(4-methoxyphenyl)-ethyl]cyclohexanol
Clinical data
Trade names	Effexor XR, Effexor, Trevilor
AHFS/Drugs.com	monograph
Licence data	US Daily Med:link
Pregnancy category	AU: B2 US: C
Legal status	AU:Prescription Only (S4) CA: ℞-only UK:POM US:℞-only
Routes of administration	Oral
Pharmacokinetic data
Bioavailability	42±15%^[1]
Protein binding	27±2% (parent compound), 30±12% (active metabolite,desvenlafaxine)^[2]
Metabolism	Hepatic (~50% of the parent compound is metabolised on first pass through the liver)^[1]^[2]
Half-life	5±2 h (parent compound for immediate release preparations), 15±6 h (parent compound for extended release preparations), 11±2 h (active metabolite)^[1]^[2]
Excretion	Renal (87%; 5% as unchanged drug; 29% asdesvenlafaxine and 53% as other metabolites)^[1]^[2]
Identifiers
CAS Registry Number	93413-69-5
ATC code	N06AX16
PubChem	CID 5656
DrugBank	DB00285
ChemSpider	5454
UNII	GRZ5RCB1QG
ChEBI	CHEBI:9943
ChEMBL	CHEMBL637
Chemical data
Formula	C₁₇H₂₇N O₂
Molecular mass	277.402 g/mol

Derivative Type: Hydrochloride

CAS : 99300-78-4

Manufacturers’ Codes: Wy-45030

Trademarks: Effexor (Wyeth)

Molecular Formula: C17H27NO2.HCl

Molecular Weight: 313.86

Percent Composition: C 65.06%, H 8.99%, N 4.46%, O 10.20%, Cl 11.30%

Properties: White to off-white crystalline solid from methanol/ethyl acetate, mp 215-217°. Soly (mg/ml): 572 water. Partition coefficient (octanol/water): 0.43.

Melting point: mp 215-217°

Log P: Partition coefficient (octanol/water): 0.43

Derivative Type: (+)-Form

Properties: Crystals from ethyl acetate, mp 102-104°. [a]D25 +27.6° (c = 1.07 in 95% ethanol).

Melting point: mp 102-104°

Optical Rotation: [a]D25 +27.6° (c = 1.07 in 95% ethanol)

Derivative Type: (+)-Form hydrochloride

Manufacturers’ Codes: Wy-45655

Properties: Crystals from methanol/ether, mp 240-240.5°. [a]D25 -4.7° (c = 0.945 in ethanol).

Melting point: mp 240-240.5°

Optical Rotation: [a]D25 -4.7° (c = 0.945 in ethanol)

Derivative Type: (-)-Form

Properties: Crystals from ethyl acetate, mp 102-104°. [a]D25 -27.1° (c = 1.04 in 95% ethanol).

Melting point: mp 102-104°

Optical Rotation: [a]D25 -27.1° (c = 1.04 in 95% ethanol)

Derivative Type: (-)-Form hydrochloride

Manufacturers’ Codes: Wy-45651

Properties: Crystals from methanol/ether, mp 240-240.5°. [a]D25 +4.6° (c = 1.0 in ethanol).

Melting point: mp 240-240.5°

Optical Rotation: [a]D25 +4.6° (c = 1.0 in ethanol)

Therap-Cat: Antidepressant.

Keywords: Antidepressant; Serotonin Noradrenaline Reuptake Inhibitor (SNRI).

1H NMR

HSQC

Displaying image.png

1H NMR PREDICT OF HCL

Venlafaxine hydrochloride NMR spectra analysis, Chemical CAS NO. 99300-78-4 NMR spectral analysis, Venlafaxine hydrochloride H-NMR spectrum

13C NMR PREDICT OF HCL

Venlafaxine hydrochloride NMR spectra analysis, Chemical CAS NO. 99300-78-4 NMR spectral analysis, Venlafaxine hydrochloride C-NMR spectrum

Venlafaxine

BASE

Venlafaxine NMR spectra analysis, Chemical CAS NO. 93413-69-5 NMR spectral analysis, Venlafaxine H-NMR spectrum

Literature References:

Serotonin noradrenaline reuptake inhibitor (SNRI). Prepn: G. E. M. Husbands et al., EP 112669; US4535186 (1984, 1985 both to Am. Home Prods.);

and resolution of isomers: J. P. Yardley et al., J. Med. Chem. 33, 2899 (1990). Receptor binding studies: E. A. Muth et al., Biochem. Pharmacol. 35, 4493 (1986).

HPLC determn in biological fluids: D. R. Hickset al., Ther. Drug Monit. 16, 100 (1994).

Clinical pharmacokinetics: K. J. Klamerus et al., J. Clin. Pharmacol. 32, 716 (1992).

Clinical trial in major depression: E. Schweizer et al., J. Clin. Psychopharmacol. 11, 233 (1991).

Review of pharmacology and clinical efficacy in depression: S. A. Montgomery, J. Clin. Psychiatry 54, 119-126 (1993).

Clinical trial in generalized anxiety disorder: A. J. Gelenberg et al., J. Am. Med. Assoc. 283, 3082 (2000).

External links[Drug information

Diagnostic tools

The Hunter Serotonin Toxicity Criteria: simple and accurate diagnostic decision rules for serotonin toxicity

Patient experiences

P.S.
: The views expressed are my personal and in no-way suggest the views
of the professional body or the company that I represent.

COCK WILL TEACH YOU NMR

COCK SAYS MOM CAN TEACH YOU NMR

DRUG APPROVALS BY DR ANTHONY MELVIN CRASTO …..FOR BLOG HOME CLICK HERE

amcrasto@gmail.com

Simple and effective method for two-step synthesis of 2-(1,3-dithian-2-ylidene)-acetonitrile

spectroscopy, SYNTHESIS Comments Off

Apr 012015

Simple and effective method for two-step synthesis of 2-(1,3-dithian-2-ylidene)-acetonitrile

Simple and effective method for two-step synthesis of 2-(1,3-dithian-2-ylidene)-acetonitrile (75% overall yield) and molecular modeling calculation of the mechanism by B3LYP and the 6-311++G(2df,2p) basis set.

http://dx.doi.org/10.5935/0100-4042.20140308

Publicado online: dezembro 12, 2014

Método alternativo para a síntese e mecanismo de 2-(1,3-ditiano-2-ilideno)-acetonitrila

Marcelle S. Ferreira; José D. Figueroa-Villar*

Quim. Nova, Vol. 38, No. 2, 233-236, 2015

Artigo http://dx.doi.org/10.5935/0100-4042.20140308

*e-mail: jdfv2009@gmail.com

MÉTODO ALTERNATIVO PARA A SÍNTESE E MECANISMO DE 2-(1,3-DITIANO-2-ILIDENO)-ACETONITRILA

Marcelle S. Ferreira e José D. Figueroa-Villar* Departamento de Química, Instituto Militar de Engenharia, Praça General Tiburcio 80, 22290-270

Rio de Janeiro – RJ, Brasil

Recebido em 18/08/2014; aceito em 15/10/2014; publicado na web em 12/12/2014

ALTERNATIVE METHOD FOR SYNTHESIS AND MECHANISM OF 2-(1,3-DITHIAN-2-YLIDENE)-ACETONITRILE. We report an alternative method for the synthesis of 2-(1,3-dithian-2-ylidene)-acetonitrile using 3-(4-chlorophenyl)-3-oxopropanenitrile and carbon disulfide as starting materials. The methanolysis of the intermediate 3-(4-chlorophenyl)-2-(1,3-dithian-2-ylidene)-3- oxopropanenitrile occurs via three possible intermediates, leading to the formation of the product at a 75% overall yield. Molecular modeling simulation of the reaction pathway using B3LYP 6-311G++(2df,2p) justified the proposed reaction mechanism. Keywords: 2-(1,3-dithian-2-ylidene)-acetonitrile; reaction mechanism; methanolysis; molecular modeling.

3-(4-clorofenil)-2-(1,3-ditiano-2-ilideno)-3-oxopropanonitrila (3): Cristal amarelo. Rendimento: 95%, 2,80 g, pf 158-160 °C, lit.21 159-160 °C;

IV (KBr, cm-1): 2198 (CN), 1612 (C=O), 1585, 1560 (aromático), 678 cm -1 (C-S);

1H RMN (300 MHz, CDCl3) δ 2,38 (m, J 6,9, 2H, CH2); 3,01 (t, J 6,6, 2H, SCH2); 3,17 (t, J 7,2 , 2H, SCH2); 7,43 (d, J 8,5, 2H); 7,83 (d, J 8,5, 2H);

13C RMN (75 MHz, CDCl3) δ 23,9 (CH2), 30,4 (SCH2), 104,2 (CCO), 117,5 (CN), 128,9, 130,5, 135,6, 139,2 (aromático), 185,2 (C=CS), 185,4 (CO).

21…….Rudorf, W. D.; Augustin, M.; Phosphorus Sulfur Relat. Elem. 1981, 9, 329.

…………………………………….

Síntese da 2-(1,3-ditiano-2-ilideno)-acetonitrila (1) Em um balão de fundo redondo de 100 mL foram adicionados 0,400 g (1,4 mmol) de 3-(4-clorofenil)-2-(1,3-ditiano-2-ilideno)-3- -oxopropanonitrila (2) dissolvidos em 15 mL de THF seco, 0,140 g (20 mmol) de sódio e 15 mL de metanol seco sob atmosfera de nitrogênio. A mistura reacional foi mantida sob agitação à 25 °C por 48 h. Em seguida, a mistura reacional foi dissolvida em 30 mL de água destilada e extraída com acetato de etila (3 x 20 mL). A fase orgânica foi seca em sulfato de sódio anidro, filtrada e concentrada a vácuo para se obter o produto bruto, que foi purificado por cromatografia em coluna (silica gel e hexano:acetato de etila 7:3).

2-(1,3-ditiano-2-ilideno)-acetonitrila (1): Cristal branco. Rendimento: 75%, 165 mg, pf. 60-63 °C, lit1 60-62 °C;

1 H RMN (300 MHz, CDCl3) δ 2,23 (m, J 6,8, 2H, CH2); 3,01 (t, J 7,5, 2H, SCH2); 3,06 (t, J 6,9, 2H, SCH2), 5,39 (s, 1H, CH);

13C RMN (75 MHz, CDCl3) δ 22,9 (CH2), 28,7 (SCH2), 28,8 (SCH2), 90,4 (CHCN), 116,3 (CN), 163,8 (C=CS).

1………Yin, Y.; Zangh, Q.; Liu, Q.; Liu, Y.; Sun, S.; Synth. Commun. 2007, 37, 703.

CAS 113998-04-2

C6 H7 N S2
Acetonitrile, 2-(1,3-dithian-2-ylidene)-
157.26

Melting Point

60-62 °C

1H NMR predict

2-(1,3-dithian-2-ylidene)-acetonitrile

ACTUAL 1H NMR VALUES

1 H RMN (300 MHz, CDCl3)

δ 2,23 (m, J 6,8, 2H, CH2);

3,01 (t, J 7,5, 2H, SCH2);

3,06 (t, J 6,9, 2H, SCH2),

5,39 (s, 1H, CH);

……………………..

13C NMR PREDICT

ACTUAL 13C NMR VALUE

13C RMN (75 MHz, CDCl3)

δ 22,9 (CH2),

28,7 (SCH2),

28,8 (SCH2),

90,4 (CHCN),

116,3 (CN),

163,8 (C=CS)

COSY NMR PREDICT

SYNTHESIS

2-(1,3-ditiano-2-ilideno)-acetonitrila (1): Cristal branco. Rendimento: 75%, 165 mg, pf. 60-63 °C, lit1 60-62 °C;1 H RMN (300 MHz, CDCl3) δ 2,23 (m, J 6,8, 2H, CH2); 3,01 (t, J 7,5, 2H, SCH2); 3,06 (t, J 6,9, 2H, SCH2), 5,39 (s, 1H, CH);

13C RMN (75 MHz, CDCl3) δ 22,9 (CH2), 28,7 (SCH2), 28,8 (SCH2), 90,4 (CHCN), 116,3 (CN), 163,8 (C=CS).

WILL BE UPDATED WATCH OUT…………………

Departamento de Química, Instituto Militar de Engenharia, Praça General Tiburcio

Instituto Militar de Engenharia, Rio de Janeiro. BELOW

Entrada do antigo Instituto de Química da UFRGS, um prédio histórico

Equipe – Os módulos foram fabricados na Unisanta sob a supervisão do professor Luiz Renato Lia, coordenador do Curso de Engenharia Química, …

Instituto de Florestas da Universidade Federal Rural do Rio de Janeiro

Praça General Tibúrcio

Praça General Tibúrcio com o Morro da Urca ao fundo

P.S. : The views expressed are my personal and in no-way suggest the views of the professional body or the company that I represent.

Enzymatic resolution of antidepressant drug precursors in an undergraduate laboratory

drugs, spectroscopy, SYNTHESIS Comments Off

Apr 012015

Enzymatic resolution of antidepressant drug precursors in an undergraduate laboratory

EducaçãoQuim. Nova 2015, 38(2), 285-287

Enzymatic resolution of antidepressant drug precursors in an undergraduate laboratory

Luís M. R. SolanoI; Nuno M. T. LourençoII,*

This paper describes a multi-step chemo-enzymatic synthesis of antidepressant drug precursors.

http://dx.doi.org/10.5935/0100-4042.20140306

Publicado online: novembro 13, 2014

Quim. Nova, Vol. 38, No. 2, 285-287, 2015

Educação http://dx.doi.org/10.5935/0100-4042.20140306

*e-mail: nmtl@tecnico.ulisboa.pt

ENZYMATIC RESOLUTION OF ANTIDEPRESSANT DRUG PRECURSORS IN AN UNDERGRADUATE LABORATORY

Luís M. R. Solanoa and Nuno M. T. Lourençob,* a Faculdade de Farmácia da Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal b Departamento de Bioengenharia, Instituto de Biotecnologia e Bioengenharia, Instituto Superior Técnico, Av. Rovisco Pais, 1, 1049-001 Lisboa, Portugal

Recebido em 07/07/2014; aceito em 17/09/2014; publicado na web em 13/11/2014

The use of biocatalysts in synthetic chemistry is a conventional methodology for preparing enantiomerically enriched compounds. Despite this fact, the number of experiments in chemical teaching laboratories that demonstrate the potential of enzymes in synthetic organic chemistry is limited. We describe a laboratory experiment in which students synthesized a chiral secondary alcohol that can be used in the preparation of antidepressant drugs. This experiment was conducted by individual students as part of a Drug Synthesis course held at the Pharmacy Faculty, Lisbon University. This laboratory experiment requires six laboratory periods, each lasting four hours. During the first four laboratory periods, students synthesized and characterized a racemic ester using nuclear magnetic resonance spectroscopy and gas chromatography. During the last two laboratory periods, they performed enzymatic hydrolysis resolution of the racemic ester using Candida antarctica lipase B to yield enantiomerically enriched secondary alcohol. Students successfully prepared the racemic ester with a 70%-81% overall yield in three steps. The enzymatic hydrolysis afforded (R)- secondary alcohol with good enantioselectivity (90%–95%) and reasonable yields (10%–19%). In these experiments, students were exposed to theoretical and practical concepts of aromatic acylation, ketone reduction, esterification, and enzymatic hydrolysis. Keywords: sec-alcohols; esters; lípase; enantiomers; resolution.

READ AT

http://quimicanova.sbq.org.br/imagebank/pdf/v38n2a20.pdf