PF-610355
- Molecular Formula C34H39N3O6S
- Average mass 617.755 Da
PF 610655, PF-00610355; PF-610,355
- 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
Abstract
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
Abstract
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
- 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 3853534
. PMID 23323609. - 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 3085864. PMID 21232045.
- Jump up^ “Pfizer Pipeline as of January 27, 2010” (PDF). Pfizer Inc. p. 6. Retrieved 9 April 2016.
- 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.
- Jump up^ Acton, Q. Ashton (ed.). Issues in Medical Chemistry. 2011 Edition. ScholarlyEditions. ISBN 978-1-464-96440-4.
- Jump up^ “AdisInsight: PF 610355”. Springer International Publishing AG. Retrieved 25 March 2016.
- 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.
 |
|
| 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 |
|
| Identifiers | |
| CAS Number | 862541-45-5 |
| ATC code | None |
| PubChem | CID 11505444 |
| ChemSpider | 9680243  |
| UNII | ZH5SMU97AJ |
| ChEMBL | CHEMBL1240967 |
| Chemical data | |
| Formula | C34H39N3O6S |
| Molar mass | 617.76 g·mol−1 |
///////////PF 610355