New Drug Approvals

Home » Uncategorized » EVP 4593

EVP 4593

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

ORGANIC SPECTROSCOPY

Read all about Organic Spectroscopy on ORGANIC SPECTROSCOPY INTERNATIONAL 

Categories

Blog Stats

  • 4,186,346 hits

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,792 other subscribers

add to any

Share

QNZ

Image result for EVP 4593

EVP4593; EVP 4593; EVP-4593

M.Wt 356.42 545380-34-5; QNZ (EVP4593); QNZ; 6-Amino-4-(4-phenoxyphenylethylamino)quinazoline; N4-(4-phenoxyphenethyl)quinazoline-4,6-diamine;
Formula C₂₂H₂₀N₄O
CAS No 545380-34-5

QNZ(EVP4593) is a derivative of 6-aminoquinazoline class that has been previously isolated as an inhibitor of PMA/PHA-induced NF-κB pathway activation in Jurkat cells (IC50= 9 nM).

QNZ(EVP4593) is a derivative of 6-aminoquinazoline class that has been previously isolated as an inhibitor of PMA/PHA-induced NF-κB pathway activation in Jurkat cells (IC50= 9 nM).
IC50 Value: 9 nM [1]
Target: NF-kB signaling
in vitro: The efficacy of EVP4593 was dose-dependent in the range between 100 uM and 400 uM in the fly food. The EVP4593 had no significant effect on climbing performance of HD flies at 50 ?M. The EVP4593 had no toxic effects on Drosophila in the range of concentrations tested in our assays (50 – 400 ?M) [1]. Addition of 300 nM of EVP4593 resulted in strong attenuation of SOC Ca2+ influx in YAC128 MSN neurons. On average the amplitude of SOC Ca2+ entry in YAC128 MSN was reduced from 0.30 ± 0.02 (n = 29) in the presence of DMSO control to 0.11 ± 0.02 (n = 54) in the presence of 300 nM of EVP4593 (p < 0.001).
in vivo:

Paper

Identification of 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine as a novel, highly potent and specific inhibitor of mitochondrial complex I

Author affiliations

Abstract

By probing the quinone substrate binding site of mitochondrial complex I with a focused set of quinazoline-based compounds, we identified substitution patterns as being critical for the observed inhibition. The structure activity relationship study also resulted in the discovery of the quinazoline 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine (EVP4593) as a highly potent inhibitor of the multisubunit membrane protein. EVP4593 specifically and effectively reduces the mitochondrial complex I-dependent respiration with no effect on the respiratory chain complexes II–IV. Similar to established Q-site inhibitors, EVP4593 elicits the release of reactive oxygen species at the flavin site of mitochondrial complex I. Recently, EVP4593 was nominated as a lead compound for the treatment of Huntingtons disease. Our results challenge the postulated primary mode-of-action of EVP4593 as an inhibitor of NF-κB pathway activation and/or store-operated calcium influx.

Graphical abstract: Identification of 4-N-[2-(4-phenoxyphenyl)ethyl]quinazoline-4,6-diamine as a novel, highly potent and specific inhibitor of mitochondrial complex I
PAPER
Bioorganic & Medicinal Chemistry (2003), 11(3), 383-391.

Abstract

We disclose here a new structural class of low-molecular-weight inhibitors of NF-κB activation that were designed and synthesized by starting from quinazoline derivative 6a. Structure–activity relationship (SAR) studies based on 6a elucidated the structural requirements essential for the inhibitory activity toward NF-κB transcriptional activation, and led to the identification of the 6-amino-4-phenethylaminoquinazoline skeleton as the basic framework. In this series of compounds, 11q, containing the 4-phenoxyphenethyl moiety at the C(4)-position, showed strong inhibitory effects on both NF-κB transcriptional activation and TNF-α production. Furthermore, 11q exhibited an anti-inflammatory effect on carrageenin-induced paw edema in rats.


Compound 11q exhibited a highly inhibitory activity toward NF-κB activation and also showed an anti-inflammatory effect.

Image for unlabelled figure
11q (72 mg, 77% yield):
mp 168–170 C;
1 H NMR (DMSO-d6) d 8.33 (br s, 2H), 7.45 (d, J=8.9 Hz, 1H), 7.40–7.34 (m, 2H), 7.28 (d, J=8.6 Hz, 2H), 7.20–7.07 (m, 3H), 6.98–6.92 (m, 4H), 5.59 (br s, 2H), 3.79–3.72 (m, 2H), 2.95 (t, J=7.3 Hz, 2H);
MS (TOF) m/z 357 (M + H)+; anal. calcd for C22H20N4O 1.0H2O: C, 70.57; H, 5.65; N, 14.96. Found: C, 70.48; H, 5.60; N, 14.87.
REF
Bioorganic & Medicinal Chemistry (2003), 11(18), 3869-3878.
JP 2004059454
 CN 1709259
Bioorganic & Medicinal Chemistry Letters (2009), 19(19), 5665-5669
Journal of Medicinal Chemistry (2014), 57(6), 2247-2257
Patent ID Patent Title Submitted Date Granted Date
US2006188938 Compounds for inhibiting beta-amyloid production and methods of identifying the compounds 2006-08-24
US2007037855 Compounds for inhibiting beta-amyloid production and methods of identifying the compounds 2007-02-15
US2007185130 Compounds for inhibiting beta-amyloid production and methods of identifying the compounds 2007-08-09
US2007191409 Compounds for inhibiting beta-amyloid production and methods of identifying the compounds 2007-08-16
US2008058330 Compounds and Combinations Thereof for Inhibiting Beta-Amyloid Production and Methods of Use Thereof 2008-03-06
US2009082371 Treatment of Viral Disease and Cancer With Nf-kappaB Inhibitors 2009-03-26
US2010016218 CONTROLLED-RELEASE APOPTOSIS MODULATING COMPOSITIONS AND METHODS FOR THE TREATMENT OF OTIC DISORDERS 2010-01-21
US2010022661 CONTROLLED RELEASE COMPOSITIONS FOR MODULATING FREE-RADICAL INDUCED DAMAGE AND METHODS OF USE THEREOF 2010-01-28
US2010215735 Compounds for Inhibiting Beta-Amyloid Production and Methods of Identifying the Compounds 2010-08-26
US2010216784 Compounds for Inhibiting Beta-Amyloid Production and Methods of Identifying the Compounds 2010-08-26
Patent ID Patent Title Submitted Date Granted Date
US2010087374 Methods for Treatment and Diagnosis of Pulmonary Diseases Based on the Expression of SERCA2 Protein 2009-10-05 2010-04-08
US2009177228 Coated suture thread and production thereof 2006-02-21 2009-07-09
US2008139457 Therapeutic compositions comprising chorionic gonadotropins and HMG CoA reductase inhibitors 2006-09-14 2008-06-12
US2014243425 CONTROLLED RELEASE COMPOSITIONS FOR MODULATING FREE-RADICAL INDUCED DAMAGE AND METHODS OF USE THEREOF 2014-05-01 2014-08-28
US2013202537 COMPOSITIONS FOR LABELING NERVES AND METHODS OF USE 2011-09-02 2013-08-08
US2013078224 INDUCTION/MONITORING OF ARTERIOGENESIS USING SDF1 AND PDGFB OR INHIBITION OF PHD2 2011-03-30 2013-03-28
US2012277199 Modulation of Gel Temperature of Poloxamer-Containing Formulations 2010-10-19 2012-11-01
US2012134922 PEPTIDES WHOSE UPTAKE IN CELLS IS CONTROLLABLE 2010-07-15 2012-05-31
US2012134931 PEPTIDES WHOSE UPTAKE IN CELLS IS CONTROLLABLE 2010-07-15 2012-05-31
US8685372 Peptides and aptamers for targeting of neuron or nerves 2010-04-15 2014-04-01
Patent ID Patent Title Submitted Date Granted Date
US2015297598 METHODS FOR TREATING RENAL DISEASE 2013-11-20 2015-10-22
US2015353604 COMPOSITIONS FOR LABELING NERVES AND METHODS OF USE 2015-06-10 2015-12-10
US2015359902 PRETARGETED ACTIVATABLE CELL PENETRATING PEPTIDE WITH INTRACELLULARLY RELEASABLE PRODRUG 2014-01-29 2015-12-17
US2016160263 PERSONALIZED PROTEASE ASSAY TO MEASURE PROTEASE ACTIVITY IN NEOPLASMS 2015-10-02 2016-06-09
US2016199446 CONTROLLED-RELEASE APOPTOSIS MODULATING COMPOSITIONS AND METHODS FOR THE TREATMENT OF OTIC DISORDERS 2016-01-19 2016-07-14

//////////

C1=CC=C(C=C1)OC2=CC=C(C=C2)CCNC3=NC=NC4=C3C=C(C=C4)N


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

This site uses Akismet to reduce spam. Learn how your comment data is processed.

DR ANTHONY CRASTO

Follow New Drug Approvals on WordPress.com

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 2,792 other subscribers
DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO Ph.D

DR ANTHONY MELVIN CRASTO, Born in Mumbai in 1964 and graduated from Mumbai University, Completed his Ph.D from ICT, 1991,Matunga, Mumbai, India, in Organic Chemistry, The thesis topic was Synthesis of Novel Pyrethroid Analogues, Currently he is working with AFRICURE PHARMA as ADVISOR, earlier assignment was with GLENMARK LIFE SCIENCES LTD, as CONSUlTANT, Retired from GLENMARK in Jan2022 Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 32 plus yrs, Prior to joining Glenmark, he has worked with major multinationals like Hoechst Marion Roussel, now Sanofi, Searle India Ltd, now RPG lifesciences, etc. He has worked with notable scientists like Dr K Nagarajan, Dr Ralph Stapel, Prof S Seshadri, etc, He did custom synthesis for major multinationals in his career like BASF, Novartis, Sanofi, etc., He has worked in Discovery, Natural products, Bulk drugs, Generics, Intermediates, Fine chemicals, Neutraceuticals, GMP, Scaleups, etc, he is now helping millions, has 9 million plus hits on Google on all Organic chemistry websites. His friends call him Open superstar worlddrugtracker. His New Drug Approvals, Green Chemistry International, All about drugs, Eurekamoments, Organic spectroscopy international, etc in organic chemistry are some most read blogs He has hands on experience in initiation and developing novel routes for drug molecules and implementation them on commercial scale over a 32 PLUS year tenure till date Feb 2023, Around 35 plus products in his career. He has good knowledge of IPM, GMP, Regulatory aspects, he has several International patents published worldwide . He has good proficiency in Technology transfer, Spectroscopy, Stereochemistry, Synthesis, Polymorphism etc., He suffered a paralytic stroke/ Acute Transverse mylitis in Dec 2007 and is 90 %Paralysed, He is bound to a wheelchair, this seems to have injected feul in him to help chemists all around the world, he is more active than before and is pushing boundaries, He has 100 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 100 Lakh plus views on dozen plus blogs, 227 countries, 7 continents, He makes himself available to all, contact him on +91 9323115463, email amcrasto@gmail.com, Twitter, @amcrasto , He lives and will die for his family, 90% paralysis cannot kill his soul., Notably he has 38 lakh plus views on New Drug Approvals Blog in 227 countries......https://newdrugapprovals.wordpress.com/ , He appreciates the help he gets from one and all, Friends, Family, Glenmark, Readers, Wellwishers, Doctors, Drug authorities, His Contacts, Physiotherapist, etc He has total of 32 International and Indian awards

Personal Links

View Full Profile →

TWITTER

  • RT @IndiaDST: The 2nd SCO Young Scientists Conclave #SCO_YSC is being hosted @jncasr , an autonomous institute of @IndiaDST , at its campus… 20 hours ago
  • RT @SciUp: Our Understanding Polymorphism online course is only a week away! This five-session course aims to give chemists and engineers a… 20 hours ago
  • RT @SciUp: Join us in Boston, US in May to get up-to-date intel on #flowchemistry. Our '5th Flow Chemistry & Continuous Processing' Confer… 20 hours ago
  • RT @SciUp: Join us online for our 'Work Up and Product Isolation' short course on 23-24 February & you will lean how to design simple and p… 20 hours ago
  • RT @thomasraji: Happy Birthday Mummyji !! Thanks for all your support and your invaluable life lessons.😍😍🎂💐💐🤩 You're not getting older...… 20 hours ago
  • RT @GuwahatiNiper: 74वें गणतंत्र दिवस कार्यक्रम की झलकियां। Glimpses of the 74th Republic Day programme. @Pharmadept @rajneeshtingal @bhagw1 day ago
  • RT @dst_neelima: DST supported NCoE on CCU at IITB was the knowledge partner in the parallel event organised by ETWG G20 on CCUS on 5 th Fe… 1 day ago
  • RT @dst_neelima: Glad to represent DST India In an International Conference on CCUS organised as a parallel event to Energy Transition Work… 1 day ago
  • Glimpse of 2nd National One Day Symposium on “Drug Discovery Research in India: Current State and Future Prospects… twitter.com/i/web/status/1… 2 days ago
  • RT @africureonline: World Cancer Day is observed annually on February 4th to raise awareness about the impact of cancer on individuals and… 2 days ago
  • RT @CSIRCIMAP: Activity 13: Dr N Kalaiselvi, DG CSIR & Secretary, DSIR under #CSIR_OneWeekOneLab inaugurated the ‘High Throughput Instrumen… 3 days ago
  • Career counseling to pharma students, At Govindrao Nikam College Of Pharmacy Sawarde,Tal - Chiplun, Ratnagiri, Mh 4… twitter.com/i/web/status/1… 3 days ago
  • RT @bluetech_media: We are proud to welcome Dr.@Anthony Melvin Crasto Advisor Africure Pharma, Global A WDT API INT RnD, Ex Glenmark LS, Wo… 3 days ago
  • Meet me at Global PHT 2023. as Guest of honor and speaker 𝐆𝐥𝐨𝐛𝐚𝐥 𝐏𝐡𝐚𝐫𝐦𝐚 𝐇𝐞𝐚𝐥𝐭𝐡𝐜𝐚𝐫𝐞 𝐓𝐞𝐜𝐡𝐧𝐨𝐥𝐨𝐠𝐲 𝐄𝐱𝐩𝐨 & 𝐒𝐮𝐦𝐦𝐢𝐭 𝟐𝟎𝟐𝟑… twitter.com/i/web/status/1… 4 days ago
  • Lifetime achievement award nomination at GlobalPHT 2023 𝐆𝐥𝐨𝐛𝐚𝐥 𝐏𝐡𝐚𝐫𝐦𝐚 𝐇𝐞𝐚𝐥𝐭𝐡𝐜𝐚𝐫𝐞 𝐓𝐞𝐜𝐡𝐧𝐨𝐥𝐨𝐠𝐲 𝐄𝐱𝐩𝐨 & 𝐒𝐮𝐦𝐦𝐢𝐭 (𝐆𝐥𝐨𝐛𝐚𝐥… twitter.com/i/web/status/1… 4 days ago

bloglovin

Follow my blog with Bloglovin The title of your home page You could put your verification ID in a comment Or, in its own meta tag Or, as one of your keywords Your content is here. The verification ID will NOT be detected if you put it here.
%d bloggers like this: