PF-610355

• Molecular Formula C₃₄H₃₉N₃O₆S
• Average mass 617.755 Da

PF 610655, PF-00610355; PF-610,355

862541-45-5  cas

• 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

PF-610355

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
UNII	ZH5SMU97AJ
ChEMBL	CHEMBL1240967
Chemical data
Formula	C34H39N3O6S
Molar mass	617.76 g·mol−1

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