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Pranidipine

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File:Pranidipine structure.svg

Pranidipine , OPC-13340, FRC 8411

Acalas®

NDA Filing in Japan

A calcium channel blocker potentially for the treatment of angina pectoris and hypertension.

CAS No. 99522-79-9

  • Molecular FormulaC25H24N2O6
  • Average mass448.468
methyl (2E)-3-phenylprop-2-en-1-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Methyl-(2E)-3-phenyl-2-propen-1-yl-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridindicarboxylat  (E)-Cinnamyl methyl (±)-1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate
Methyl cinnamyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydro-3,5-pyridinedicarboxylate
trans-Cinnamyl methyl 4-(3-nitrophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, methyl (2E)-3-phenyl-2-propen-1-yl ester

Pranidipine is a calcium channel blocker. It is a long acting calcium channel antagonist of the dihydropyridine group.[1]

 

PATENT

EP 0173126

http://www.google.com/patents/EP0173126A1?cl=en

PAPER

Der Pharmacia Sinica, 2014, 5(1):11-17

pelagiaresearchlibrary.com/der-pharmacia-sinica/vol5-iss1/DPS-2014-5-1-11-17.pdf

 

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Preparation of Pranidipine Hydrochloride(2):
To a suspension of (Z)-2-(3-nitrobenzylidene)-3-oxobutanoic acid(3) (1.2 kg, 5.10 mol) in dichloromethane (6 L)
was added triethylamine(0.77 kg, 7.65 mol) and cinnamyl chloride (0.85 kg, 5.61 mol). The reaction mixture was
heated to 45°C and maintained for 2 hrs. The suspension was cooled to 25 to 30°C and washed with 2.4 Lof DM
water. DCM layer was separated and concentrated under vacuum below 40°C. The concentrated mass was dissolved
in 7.2 L isopropyl alcohol and methyl-3-amino crotonate (0.52 kg, 4.5mol) was added to it. Temperatureof reaction
mixture was slowly raised to 70°C and maintained for 8 hours. Reaction mass was concentrated under vacuum
below 40°C.To the crude residue, ethyl acetate-HCl(0.28 kg, 7.6 mol) was added and the reaction mixture was
stirred for 24 hours at 25°C-30°C. Reaction mixturewas filtered and the solid residue was dried under
vacuum toafford 1.6 kg of Pranidipine hydrochloride (2)in 85% yield with 98 % purity.
1H-NMR(DMSO):
δ2.29 (s, 3H),2.32 (s, 3H), 3.55 (s, 3H), 4.60-4.74 (m, 2H), 5.04(s, 1H), 6.26-6.33 (m, 1H), 6.50 (d, 1H), 7.24-7.3
8 (m, 5H), 7.53(t, 1H), 7.63 (d,1H), 7.98-8.01 (m, 1H), 9.08 (brs, 1H)
 
Preparation of (Z)-2-(3-nitrobenzylidene)-3-oxobutanoic acid(3):
To a suspension of (Z)-t-butyl 2-(3-nitrobenzylidene)-3-oxobutanoate(10) (1.5 kg, 5.14 mol) in dichloromethane
(7.5 L) was added trifluoroacetic acid (1.76 kg, 15.44 mol) and reaction mass was stirred at 25°C to 30°C for 24 hrs.
The reaction mass was concentrated under vacuum below 40°C and stripped with toluene. The concentratedmass
was dissolved in 4.5 L toluene and the solution wasstirred for 8 hours at 25°C to 30°C. Reaction mixture was
filtered and solid washed with toluene and dried at35°C to 40°C to give 1.152 kg of (Z)-2-(3-nitrobenzylidene)-3-
oxobutanoic acid(3) in 96 % yield. M.P: 120°C; Mol.Wt: 235.20; Mol.Formula: C11H9NO5;1H-NMR(DMSO):
δ2.46 (s, 3H), 7.76-7.83 (m, 2H), 8.02 (d, 1H), 8.28-8.31 (dd, 1H), 8.51 (s, 1H), 13.63 (brs, 1H).Anal.Calcd for
C11H10NO5 : C, 55.93; H, 4.27; N, 5.93. Found: C, 56.19;H, 4.09; N, 6.27
Preparation of (Z)-tertiary- butyl 2-(3-nitrobenzylidene)-3-oxobutanoate(10):
To a suspension of 3-nitrobenzaldehyde(5) (1 kg, 6.61 mol) in isopropyl alcohol (6 L) was addedt-butylacetoacetate (1.14 kg, 7.27 mol),piperidine (0.12 kg, 1.32 mol) and acetic acid (0.79 kg, 1.32 mol). The reactionmass was stirred at 25°C to 30°C for 6 hrs. The suspension was cooled to -5 to 0°C, filtered, residuewashed withisopropyl alcohol and dried at 35°C to 40°C to give
1.750 kg of (Z)-t-butyl 2-(3-nitrobenzylidene)-3-oxobutanoate(10)in 91% yield; M.P: 80°C; Mol. Wt: 291.31; Mol.Formula: C15H17NO5
1H-NMR(CDCl3):
δ1.55(s, 9H), 2.44 (s, 3H), 7.50 (s, 1H),7.59 (t, 1H),7.80 (d, 1H), 8.24- 8.27 (dd,J=1H),δ8.41 (t, 1H).
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Patent Submitted Granted
Process for the preparation of 1,4 – dihydropyridines and novel 1,4-dihydropyridines useful as therapeutic agents [US2003230478] 2003-12-18
Advanced Formulations and Therapies for Treating Hard-to-Heal Wounds [US2014357645] 2014-08-19 2014-12-04
METHODS OF TREATING CARDIOVASCULAR AND METABOLIC DISEASES [US2014322199] 2012-08-06 2014-10-30
Protein Carrier-Linked Prodrugs [US2014323402] 2012-08-10 2014-10-30
sGC STIMULATORS [US2014323448] 2014-04-29 2014-10-30
TREATMENT OF ARTERIAL WALL BY COMBINATION OF RAAS INHIBITOR AND HMG-CoA REDUCTASE INHIBITOR [US2014323536] 2012-12-07 2014-10-30
Agonists of Guanylate Cyclase Useful For the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders [US2014329738] 2014-03-28 2014-11-06
METHODS, COMPOSITIONS, AND KITS FOR THE TREATMENT OF CANCER [US2014335050] 2012-05-25 2014-11-13
ROR GAMMA MODULATORS [US2014343023] 2012-09-18 2014-11-20
High-Loading Water-Soluable Carrier-Linked Prodrugs [US2014296257] 2012-08-10 2014-10-02

 

Pranidipine.png

Publication Number Publication Date IPCR Assignee/Applicant Structure hits Tools
1.

US-20150342954-A1

2015-12-03
2-BENZYL, 3-(PYRIMIDIN-2-YL) SUBSTITUTED PYRAZOLES USEFUL AS SGC STIMULATORS
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
2.

EP-2558474-B1

2015-11-25
2, 4-PYRIMIDINEDIAMINE COMPOUNDS AND PRODRUGS THEREOF AND THEIR USES
EN
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
3.

US-20150307580-A1

2015-10-29
OXYNTOMODULIN ANALOGS
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
4.

US-20150305974-A1

2015-10-29
METHODS AND DEVICES FOR TREATING HYPERTENSION
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
5.

WO-2015164658-A1

2015-10-29
METHODS AND DEVICES FOR TREATING HYPERTENSION
EN
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
6.

EP-2527360-B1

2015-10-28
Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders
EN
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
7.

WO-2015157471-A1

2015-10-15
INOS-INHIBITORY COMPOSITIONS AND THEIR USE AS BREAST CANCER THERAPEUTICS
EN
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
8.

US-20150284411-A1

2015-10-08
NOVEL AZABENZIMIDAZOLE HEXAHYDROFURO[E,2-B]FURAN DERIVATIVES
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
9.

US-20150283202-A1

2015-10-08
AGONISTS OF GUANYLATE CYCLASE USEFUL FOR THE TREATMENT OF HYPERCHOLESTEROLEMIA, ATHEROSCLEROSIS, CORONARY HEART DISEASE, GALLSTONE, OBESITY AND OTHER CARDIOVASCULAR DISEASES
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1
10.

US-9150512-B2

2015-10-06
Tricyclic lactam derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors
COC(=O)C1=C(C)NC(C)=C(C1C1=CC(=CC=C1)[N+]([O-])=O)C(=O)OC\C=C\C1=CC=CC=C1

References

Jin Yang, Keisuke Fukuo, Shigeto Morimoto, Tadaaki Niinobu, Toshimitsu Suhara, Toshio Ogihara (2000). “Pranidipine Enhances the Action of Nitric Oxide Released From Endothelial Cells”. Hypertension 35: 82–85. doi:10.1161/01.hyp.35.1.82.

 

http://pelagiaresearchlibrary.com/der-pharmacia-sinica/vol5-iss1/DPS-2014-5-1-11-17.pdf………NICARDIPINE

Pranidipine
Pranidipine structure.svg
Names
IUPAC name

methyl (2E)-phenylprop-2-en-1-yl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
Other names

2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid O5-methyl O3-[(E)-3-phenylprop-2-enyl] ester
Identifiers
99522-79-9 Yes
ChEMBL ChEMBL1096842 
ChemSpider 4940726 
Jmol interactive 3D Image
MeSH C048161
PubChem 6436048
UNII 9DES9QVH58 Yes
Properties
C25H24N2O6
Molar mass 448.46786

 

//////////

CC1=C(C(C(=C(N1)C)C(=O)OCC=CC2=CC=CC=C2)C3=CC(=CC=C3)[N+](=O)[O-])C(=O)OC

see dipine series………..http://organicsynthesisinternational.blogspot.in/p/dipine-series.html

Nilvadipine – Wikipedia, the free encyclopedia

manidipine

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DR ANTHONY CRASTO

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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 GLENMARK PHARMACEUTICALS LTD, Research Centre as Principal Scientist, Process Research (bulk actives) at Mahape, Navi Mumbai, India. Total Industry exp 29 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 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 29 year tenure till date Aug 2016, Around 30 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 9 million plus hits on Google, 2.5 lakh plus connections on all networking sites, 25 Lakh plus views on dozen plus blogs, 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 13 lakh plus views on New Drug Approvals Blog in 212 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

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