NicOx : Garufi ... e la Rivoluzione Pharma (8 lettori)
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viralic
Forumer storico
..........da parte mia è tutto chiaro!!!......Non farò mai più illazioni circa supposto trading da parte del summenzionato Forumer!!Chiedo scusa al diretto interessato per i dubbi avanzati in passato.
Tutti possono fare errori di valutazione.......chi sbaglia ad ascoltare "vocine" rivelatisi errate, e chi sbaglia a non credere ad affermazioni pubbliche. L'importante e saperlo riconoscere e CHIEDERE SCUSA !!!
Non so se mi abbia messo nella lista ignora....nel qual caso qualcuno volenteroso gli faccia pervenire il mio post....Grazie.
doctor NO
NO nel DNA
NicOx Research Institute Hier à 19:47
Synthesis of novel nitric oxide (NO)-releasing esters of timolol
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Valerio Chirolia, , , Minerva R. Batugob, Stefano Biondia, Annalisa Bonfantia, Stefania Brambillaa, David C. Galeb, Lin Lib, Daniela Migliettaa, Fabio Nicolia, Ganesh A. Prassanab, Daniela Ronchettia, William F. Vernierb and Wesley K.M. Chongb
aNicOx Research Institute, Via Ariosto 21, 20091 Bresso (Milan), Italy
bPfizer Global Research and Development-La Jolla, 10770 Science Center Drive, San Diego, CA 92121, USA
Received 26 February 2009; revised 20 March 2009; accepted 23 March 2009. Available online 27 March 2009.
Abstract
A novel class of timolol derivatives with nitric oxide (NO)-donating moieties achieved chemical stability yet under physiologically relevant conditions released timolol and NO. Hindered esters A were designed and synthesized, whose ‘triggered’ release relied on enzymatic hydrolysis of the nitrate ester in A to B, that in turn cyclized to liberate timolol.
Graphical abstract
Full-size image (27K)
Keywords: Beta-blocker, Vasorelaxation assay, Nitric oxide conjugate, Timolol, Trigger
Article Outline
Acknowledgements
References
Figure 1. 3-Dimensional model8 of timolol O-(2,6-dimethoxybenzoate), highlighting in the drawn oval, the carbonyl hindered to nucleophilic substitution by the flanking methoxy groups.
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Scheme 1. Hypothetical mechanism for the release of timolol: the triggering strategy undergoing through intramolecular cyclization reaction.
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Table 1.
Chemical stability in solution (buffer pH 5.7, Tween 80 0.5%, BAK 0.02%, T = room temperature) and incubation with rabbit corneal homogenate esterase liability of timolol benzoates 1–10
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a Ratio = (Area% tx/Area% t0)% by HPLC.
b Enzymatic liability was determined in presence of rabbit corneal homogenate (protein concentration was adjusted to 1 mg/mL with MCBD 153 medium obtained from Sigma–Aldrich) through the determination of timolol released into the incubating buffer at 37 °C over time. Specifically, timolol content was determined assessing the displacing activity on recombinant human β-receptors labelled with l-[4,6-propyl-3H]dihydro alprenolol16 of corneal extracts previously exposed to vehicle of test compounds.
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Table 2.
Chemical stability in solution (buffer pH 5.7, Tween 80 0.5%, BAK 0.02%, T = room temperature) and enzymatic liability of compounds 11–15
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a Ratio = (Area % tx/Area % t0) %.
b Enzymatic liability was determined as specified in Table 1.
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Table 3.
Vasodilating potency of timolol, ISMN,24 trigger compounds 11 and 12 in presence and absence of the guanylate cyclase inhibitor ODQ (10 μM)
Vasorelaxant potency was determined in rabbit aortic rings precontracted with 3 μM methoxamine. EC50 (effective concentration giving 50% of response) were estimated for each test compound from the logic curve obtained by plotting the percentage of vasorelaxant effects as a function of concentration. The EC50 could not be calculated for compounds with efficacy below 50% at the highest testable concentration of 100 μM (NC). Results are expressed as mean ± SEM of four independent experiments.
p < 0.05 versus condition in absence of ODQ.
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Corresponding author. Tel.: +39 0261036326.
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GULY GULY
lo vedi che non stai attento!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! questa nuova molecola credo venga sviluppata con Nicox al posto del farmaco per il glaucoma abbandonato un'anno fa Io posto le notizie utili ma il problema è che a te servono veramente le vignette tanto il risultato è lo stesso
doctor NO
NO nel DNA
http://www.bbbiotech.ch/fileadmin/u...a/Rapporti_finanziari/2009/PM_BIO_Q109_IT.pdf
loro della BB biotech hanno già capito e sono passati dallo 0,7 al 1% del loro portafoglio investito in Nicox<<<<<leggete il report ed in particolar modo l'ultima parte su potenziali blockbusters biotech<<<<<<<<<<<<<<<<<<<<<<<<<<<<< analizzado il report hanno sempre un milione di azioni e sono al 2,1 % di capitale di nicox!!!!!!!!!!!!!
loro della BB biotech hanno già capito e sono passati dallo 0,7 al 1% del loro portafoglio investito in Nicox<<<<<leggete il report ed in particolar modo l'ultima parte su potenziali blockbusters biotech<<<<<<<<<<<<<<<<<<<<<<<<<<<<< analizzado il report hanno sempre un milione di azioni e sono al 2,1 % di capitale di nicox!!!!!!!!!!!!!
ugotega
Forumer storico
doctor NO
NO nel DNA
(WO/2009/049961) NOUVEAUX DÉRIVÉS D'ASPIRINE DONNEURS NO
FRUTTERO, Roberta [IT/IT]; (IT) (US Seulement ).
GASCO, Alberto [IT/IT]; (IT) (US Seulement ).
LAZZARATO, Loretta [IT/IT]; (IT) (US Seulement ).
DONNOLA, Monica [IT/IT]; (IT) (US Seulement ).
ROLANDO, Barbara [IT/IT]; (IT) (US Seulement ).
BIONDI, Stefano [IT/IT]; (IT) (US Seulement ).Inventeurs:FRUTTERO, Roberta; (IT).
GASCO, Alberto; (IT).
LAZZARATO, Loretta; (IT).
DONNOLA, Monica; (IT).
ROLANDO, Barbara; (IT).
BIONDI, Stefano; (IT).Mandataire:BARCHIELLI, Giovanna; Nicox Research Institute Srl, Via L. Ariosto 21, I-20091 Bresso (Milano) (IT).Données relatives
à la priorité:60/960,912 19.10.2007 USTitre:(FR) NOUVEAUX DÉRIVÉS D'ASPIRINE DONNEURS NO
(EN) NEW NO-DONOR ASPIRIN DERIVATIVES
Abrégé:
États désignés:AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
Organisation régionale africaine de la propriété intellectuelle (ARIPO) (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Organisation eurasienne des Brevets (OEAB) (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
Organisation européenne des brevets (OEB) (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR)
Organisation africaine de la propriété intellectuelle (OAPI) (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). Langue de publication:anglais (EN) Langue de dépôt:anglais (EN)
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FRUTTERO, Roberta [IT/IT]; (IT) (US Seulement ).
GASCO, Alberto [IT/IT]; (IT) (US Seulement ).
LAZZARATO, Loretta [IT/IT]; (IT) (US Seulement ).
DONNOLA, Monica [IT/IT]; (IT) (US Seulement ).
ROLANDO, Barbara [IT/IT]; (IT) (US Seulement ).
BIONDI, Stefano [IT/IT]; (IT) (US Seulement ).Inventeurs:FRUTTERO, Roberta; (IT).
GASCO, Alberto; (IT).
LAZZARATO, Loretta; (IT).
DONNOLA, Monica; (IT).
ROLANDO, Barbara; (IT).
BIONDI, Stefano; (IT).Mandataire:BARCHIELLI, Giovanna; Nicox Research Institute Srl, Via L. Ariosto 21, I-20091 Bresso (Milano) (IT).Données relatives
à la priorité:60/960,912 19.10.2007 USTitre:(FR) NOUVEAUX DÉRIVÉS D'ASPIRINE DONNEURS NO
(EN) NEW NO-DONOR ASPIRIN DERIVATIVES
Abrégé:
(FR) La présente invention concerne des dérivés d'aspirine donneurs NO, un procédé destiné à leur préparation et des compositions pharmaceutiques les contenant.
(EN) The present invention refers to new NO-donors aspirin derivatives, a process for their preparation and pharmaceutical compositions containing them.
(EN) The present invention refers to new NO-donors aspirin derivatives, a process for their preparation and pharmaceutical compositions containing them.
États désignés:AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RS, RU, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
Organisation régionale africaine de la propriété intellectuelle (ARIPO) (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Organisation eurasienne des Brevets (OEAB) (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
Organisation européenne des brevets (OEB) (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MT, NL, NO, PL, PT, RO, SE, SI, SK, TR)
Organisation africaine de la propriété intellectuelle (OAPI) (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG). Langue de publication:anglais (EN) Langue de dépôt:anglais (EN)
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viralic
Forumer storico
Coxi dixit:
Non so se la Nicox potrà farcela da sola, ma la situazione oggi lo permette di più che in passato. I managers delle grandi sono preda di phobos, i manager Nicox non più da tempo.
Vedremo. Comunque non torneremo a mio avviso sotto i 9 euro. Nessuno lo vuole.
Nessuno lo vuole.....forse sarebbe meglio cambiare il soggetto: Noi non lo vorremmo, evidentemente qualcuno continua a volere Nicox sotto i 9 euro !! E' la triste realtà, per il momento..in futuro vedremo........se ci sarà il partner però !!!
Non so se la Nicox potrà farcela da sola, ma la situazione oggi lo permette di più che in passato. I managers delle grandi sono preda di phobos, i manager Nicox non più da tempo.
Vedremo. Comunque non torneremo a mio avviso sotto i 9 euro. Nessuno lo vuole.
Nessuno lo vuole.....forse sarebbe meglio cambiare il soggetto: Noi non lo vorremmo, evidentemente qualcuno continua a volere Nicox sotto i 9 euro !! E' la triste realtà, per il momento..in futuro vedremo........se ci sarà il partner però !!!
doctor NO
NO nel DNA
Coxi dixit:
Non so se la Nicox potrà farcela da sola, ma la situazione oggi lo permette di più che in passato. I managers delle grandi sono preda di phobos, i manager Nicox non più da tempo.
Vedremo. Comunque non torneremo a mio avviso sotto i 9 euro. Nessuno lo vuole.
Vic osserva bene il book delle finte vendite per renderti conto di come è manipolato il titolo
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