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PF 610355 Revisited

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PF-610355

  • Molecular Formula C34H39N3O6S
  • Average mass 617.755 Da

PF 610655, PF-00610355; PF-610,355

2-[3-[2-[[(2R)-2-hydroxy-2-[4-hydroxy-3-(methylsulfonylamino)phenyl]ethyl]amino]-2-methyl-propyl]phenyl]-N-[[3-(4-hydroxyphenyl)phenyl]methyl]ethanamide
862541-45-5  cas
ChemSpider 2D Image | PF-610355 | C34H39N3O6S
  • Originator Pfizer
  • Class Antiasthmatics; Benzeneacetamides; Sulfonamides
  • Mechanism of Action Beta 2 adrenergic receptor agonists
  • Orphan Drug StatusNo
  • On Fast trackNo

Highest Development Phases

  • Discontinued Asthma; Chronic obstructive pulmonary disease

Most Recent Events

  • 11 Aug 2011 Discontinued – Phase-I for Asthma in Belgium (Inhalation)
  • 11 Aug 2011 Discontinued – Phase-II for Asthma in Sweden (Inhalation)
  • 11 Aug 2011 Discontinued – Phase-II for Asthma in Germany (Inhalation)

PF-610355 (also known as PF-00610355 or PF-610,355) is an inhalable[1] ultra-long-acting β2 adrenoreceptor agonist[2] (ultra-LABA) that was investigated as a treatment of asthma and COPD by Pfizer.[3] It utilizes a sulfonamide agonist headgroup, that confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties minimized systemic exposure following inhalation and reduced systemically-mediated adverse events.[4] Its in vivo duration on action confirmed its potential for once-daily use in humans.[5]

The investigation and development of PF-610355 were discontinued in 2011,[6] likely for strategic and regulatory reasons.[7]

 

 

PF-610355). Mp 197−199 °C.

1 H NMR (600 MHz, d6-DMSO) δ 0.89 (s, 3H), 0.91 (s, 3H), 2.54 (s, 2H), 2.59−2.68 (m, 2H), 2.89 (s, 3H), 3.44 (s, 2H), 4.31 (d, 2H), 4.42 (dd, 1H), 6.80−8.83 (m, 3H), 6.97−7.02 (m, 2H), 7.08−7.12 (m, 3H), 7.16 (t, 1H), 7.19 (d, 1H), 7.30 (t, 1H), 7.37−7.41 (m, 4H), and 8.50 (t, 1H).

13C NMR (151 MHz, d6-DMSO) δ 26.39, 26.64, 39.85, 42.22, 42.48, 46.36, 50.15, 52.71, 72.00, 115.14, 115.70, 123.76, 124.02, 124.29, 124.38, 124.76, 125.23, 126.49, 127.57, 127.63, 128.40, 128.71, 130.82, 131.13, 135.38, 135.73, 138.43, 139.94, 140.20, 149.76, 157.11, and 170.28.

HRMS (ESI): calcd (M + H)+ 618.2632, found 618.2641. Found: C, 65.70%; H, 6.33%; N, 6.71%; S, 5.24%. C34H39N3O6S·0.17H2O requires C, 65.78%; H, 6.39%; N, 6.77%; S, 5.16%

PAPER

Optimization of the Manufacturing Route to PF-610355 (2): Synthesis of the API

Chemical Research and Development, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, U.K., CT13 9NJ
Org. Process Res. Dev., 2013, 17 (2), pp 202–212
DOI: 10.1021/op300342y
Publication Date (Web): February 5, 2013
Copyright © 2013 American Chemical Society

Abstract

Abstract Image

PF-610355 is a novel inhaled β-2 adrenoreceptor agonist. Process development of the final intermediate and the API are discussed with emphasis on the control of physical properties and subsequent isolations. This includes development of a constant volume distillation and evaluation of Nutsche filtration, agitated filter drying, and centrifugation to prevent particle attrition. The optimized process employed to manufacture 100 kg of the API is described.

 

 

 

PAPER

Optimization of the Manufacturing Route to PF-610355 (1): Synthesis of Intermediate 5

Chemical Research and Development, Pfizer Global Research and Development, Ramsgate Road, Sandwich, Kent, U.K., CT13 9NJ
Org. Process Res. Dev., 2013, 17 (2), pp 193–201
DOI: 10.1021/op300341n
Publication Date (Web): February 5, 2013
Copyright © 2013 American Chemical Society

Abstract

Abstract Image

Tertiary carbinamine 5 is an isolated intermediate in the synthesis of a novel, inhaled β-2 adrenoreceptor agonist PF-610355. Process development for the key amide-formation and Ritter reactions, together with reaction understanding studies are discussed in context of the synthesis of 5. The optimized process employed to manufacture 140 kg of 5 is described, and was shown to have superior metrics to the preliminary commercial route.

References

  1. Jump up^ Diderichsen, Paul Matthias; Cox, Eugène; Martin, Steven W.; Cleton, Adriaan; Ribbing, Jakob (November 2013). “Predicted Heart Rate Effect of Inhaled PF-00610355, a Long Acting β-Adrenoceptor Agonist, in Volunteers and Patients With Chronic Obstructive Pulmonary Disease”. British Journal of Clinical Pharmacology. 76 (5): 752–62. doi:10.1111/bcp.12080. PMC 3853534free to read. PMID 23323609.
  2. Jump up^ Cazzola, Mario; Luigino Calzetta; Maria Gabriella Matera3 (May 2011). “β2-adrenoceptor agonists: current and future direction”. Br J Pharmacol. 163 (1): 4–17. doi:10.1111/j.1476-5381.2011.01216.x. PMC 3085864free to read. PMID 21232045.
  3. Jump up^ “Pfizer Pipeline as of January 27, 2010” (PDF). Pfizer Inc. p. 6. Retrieved 9 April 2016.
  4. Jump up^ Glossop, PA; Lane, CA; Price, DA; Bunnage, ME; Lewthwaite, RA; James, K; Brown, AD; Yeadon, M; Perros-Huguet, C; Trevethick, MA; Clarke, NP; Webster, R; Jones, RM; Burrows, JL; Feeder, N; Taylor, SC; Spence, FJ (23 September 2010). “Inhalation by Design: Novel Ultra-Long-Acting β2-Adrenoreceptor Agonists for Inhaled Once-Daily Treatment of Asthma and Chronic Obstructive Pulmonary Disease That Utilize a Sulfonamide Agonist Headgroup”. Journal of Medicinal Chemistry. 53 (18): 6640–52. doi:10.1021/jm1005989. PMID 20804199.
  5. Jump up^ Acton, Q. Ashton (ed.). Issues in Medical Chemistry. 2011 Edition. ScholarlyEditions. ISBN 978-1-464-96440-4.
  6. Jump up^ “AdisInsight: PF 610355”. Springer International Publishing AG. Retrieved 25 March 2016.
  7. Jump up^ Cazzola, M; Page, CP; Rogliani, P; Matera, MG (1 April 2013). “β2-Agonist Therapy in Lung Disease”. American Journal of Respiratory and Critical Care Medicine. 187 (7): 693. doi:10.1164/rccm.201209-1739PP. PMID 23348973.
PF-610355
PF-610355.svg
Systematic (IUPAC) name
N-[(4′-Hydroxy-3-biphenylyl)methyl]-2-[3-(2-{[(2R)-2-hydroxy-2-{4-hydroxy-3-[(methylsulfonyl)amino]phenyl}ethyl]amino}-2-methylpropyl)phenyl]acetamide
Clinical data
Routes of
administration
Inhalation
Legal status
Legal status
  • Development terminated
Identifiers
CAS Number 862541-45-5
ATC code None
PubChem CID 11505444
ChemSpider 9680243 Yes
UNII ZH5SMU97AJ Yes
ChEMBL CHEMBL1240967 Yes
Chemical data
Formula C34H39N3O6S
Molar mass 617.76 g·mol−1

///////////PF 610355


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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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