Process development of ABT-450 – A first generation NS3/4A protease inhibitor for HCV

Caspi, Daniel D.; Cink, Russell D.; Clyne, Dean S.; Diwan, Moiz; Engstrom, Kenneth M.; Grieme, Timothy; Mei, Jianzhang; Miller, Robert W.; Mitchell, Clifford R.; Napolitano, José G.; Nere, Nandkishor K.; Ravn, Matthew M.; Sheikh, Ahmad Y.; Wagaw, Seble; Zhang, Hongqiang

doi:10.1016/j.tet.2019.05.064

Cited by 18 publications

(38 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Multicomponent crystal forms of pharmaceuticals, especially hydrates, are frequently observed (Stahly, 2007;Cruz-Cabeza et al, 2015) and are increasingly common in recently approved drugs (Caspi et al, 2019;Cink et al, 2020;Califano et al, 2016;Brackemeyer et al, 2017;Pangan et al, 2018). Hydrates, solvates and cocrystals present challenges during development because of the implications for in vivo solubility, manufacturing and storage (Hilfiker et al, 2006;Pudipeddi & Serajuddin, 2005;Threlfall, 1995).…”

Section: Introductionmentioning

confidence: 99%

Polymorphism and surface diversity arising from stress-induced transformations – the case of multicomponent forms of carbamazepine

Rauber¹,

Arhangelskis²,

Bond³

et al. 2021

Acta Crystallogr B Struct Sci Cryst Eng Mater

Self Cite

View full text Add to dashboard Cite

Stress-induced transformations of labile multicomponent organic solids may have a significant impact on industrial manufacturing processes, for example, in the pharmaceutical field. This study considers 15 carbamazepine (CBZ) multicomponent crystal forms, with the aim of identifying the structural and surface features that drive the outcome of thermal stress-induced transformations. Analysis of the crystal structures, and specifically the degree of similarity with the CBZ polymorphs produced by desolvation-like processes, identifies some degree of correlation between structural features. In particular, mutually exclusive supramolecular motifs identified previously within CBZ crystal structures are frequently (but not invariably) preserved, and thereby provide some indication of the anticipated polymorphic outcome. This is broadly consistent with established models relating reactant and product crystal phases. Some of the CBZ multicomponent materials show surface modifications indicative of the formation of a liquid intermediate phase, which provides an alternative dissolution/recrystallization mechanism and different polymorphic outcomes compared to the direct solid–solid transformation pathway. Other cases show intermediates of varying stoichiometry and instances of chemical decomposition. Hence, the product of thermal decomposition is frequently affected by the physical properties of the coformer, such as boiling point and reactivity. This can lead to a dependence on experimental conditions, especially when events such as recrystallization, chemical decomposition of the coformer, solubilization and peritectic melting occur concomitantly. This study highlights that the overall picture is complex, even within this series of closely related materials.

show abstract

Section: Introductionmentioning

confidence: 99%

Polymorphism and surface diversity arising from stress-induced transformations – the case of multicomponent forms of carbamazepine

Rauber¹,

Arhangelskis²,

Bond³

et al. 2021

Acta Crystallogr B Struct Sci Cryst Eng Mater

Self Cite

View full text Add to dashboard Cite

show abstract

“…Grazoprevir and asunaprevir both contain vinyl-ACCA, whereas simeprevir 261 and paritaprevir 262 require its incorporation to allow for macrocyclisation through ring-closing metathesis. 263 The synthesis of vinyl-ACCA as outlined by Boehringer Ingelheim in 2005 is regarded as the gold standard for the production of this compound (Scheme 42A). 264 Their synthetic strategy involved resolution of the N-Boc-protected vinyl-ACCA methyl ester (cis-190) by Alcalase 2.4L (a Bacillus licheniformis protease formulation).…”

Section: Review Articlementioning

confidence: 99%

“…After peptide coupling of vinyl-ACCA (199), L-hydroxyproline ((2S,4R)-186) and L-6-heptenylglycine (198), ring-closing metathesis of the two terminal olefins allowed for the synthesis of paritaprevir (Scheme 44A). 263 Resolution of the N-acetylprotected racemate with acylase I afforded L-6-heptenylglycine with 499% ee on large scale. 272 Alternatively, the corresponding N-Boc-protected precursor could be resolved by subjecting its ethyl ester to protease-catalysed hydrolysis.…”

Section: Review Articlementioning

confidence: 99%

Biocatalytic routes to anti-viral agents and their synthetic intermediates

Slagman

Fessner

2021

Chem. Soc. Rev.

View full text Add to dashboard Cite

show abstract

“…RCM macrocyclization (mRCM) represents a methodology of major current interest for the production of antiviral therapeutics. 7 , 20 The first indication that even low concentrations of water might impede mRCM emerged in reactions involving the dianiline catalyst Ru-1 ( Chart 1 ). In our hands, Ru-1 was exceptionally efficient, 21 outperforming even the leading nitro-Grela catalyst Ru-2 in mRCM of challenging, highly flexible substrates bearing multiple polar sites.…”

mentioning

confidence: 99%

The Impact of Water on Ru-Catalyzed Olefin Metathesis: Potent Deactivating Effects Even at Low Water Concentrations

et al. 2021

View full text Add to dashboard Cite

Ruthenium catalysts for olefin metathesis are widely viewed as water-tolerant. Evidence is presented, however, that even low concentrations of water cause catalyst decomposition, severely degrading yields. Of 11 catalysts studied, fast-initiating examples (e.g., the Grela catalyst RuCl 2 (H 2 IMes)(=CHC 6 H 4 -2-O i Pr-5-NO 2 ) were most affected. Maximum water tolerance was exhibited by slowly initiating iodide and cyclic (alkyl)(amino)carbene (CAAC) derivatives. Computational investigations indicated that hydrogen bonding of water to substrate can also play a role, by retarding cyclization relative to decomposition. These results have important implications for olefin metathesis in organic media, where water is a ubiquitous contaminant, and for aqueous metathesis, which currently requires superstoichiometric “catalyst” for demanding reactions.

show abstract

Process development of ABT-450 – A first generation NS3/4A protease inhibitor for HCV

Cited by 18 publications

References 21 publications

Polymorphism and surface diversity arising from stress-induced transformations – the case of multicomponent forms of carbamazepine

Polymorphism and surface diversity arising from stress-induced transformations – the case of multicomponent forms of carbamazepine

Biocatalytic routes to anti-viral agents and their synthetic intermediates

The Impact of Water on Ru-Catalyzed Olefin Metathesis: Potent Deactivating Effects Even at Low Water Concentrations

Contact Info

Product

Resources

About