Pentafluoroethyllithium. Generation and use in synthesis

Gassman, Paul G.; O’Reilly, Neil J.

doi:10.1016/s0040-4039(00)95005-6

Cited by 74 publications

(18 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The sulfoximine 19 was found to be less potent by af actor of approximately 10 compared with the sulfone and did not fully meet the criteria for furtheri nv ivo characterization. However,s ulfoximine 19 exhibited an approximately eightfold improvement in aqueous solubility compared with sulfone 18 (nephelometry:7 4mgL À1 [19]v ersus 9mgL À1 [18]). Accordingly,t his derivativew as also selected for furtheri nv ivo characterization.…”

Section: Discovery Of Vilaprisanmentioning

confidence: 99%

Discovery of Vilaprisan (BAY 1002670): A Highly Potent and Selective Progesterone Receptor Modulator Optimized for Gynecologic Therapies

et al. 2018

View full text Add to dashboard Cite

Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone‐dependent. Steroidal and non‐steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the treatment of such diseases. Steroidal SPRMs, including mifepristone and ulipristal acetate, have proven effective in clinical trials. However, several steroidal SPRMs containing a dimethylamino substituent have been associated with elevated liver enzymes in patients. An earlier drug discovery program identified lonaprisan as a highly selective SPRM that did not show drug‐related change in liver enzyme activity. Building on data obtained from that work, here we describe the research program that culminated in the discovery of a novel steroidal SPRM, vilaprisan, which combines an extremely high potency with very favorable drug metabolism and pharmacokinetic properties. Vilaprisan has entered clinical development and is currently undergoing phase 3 clinical trials.

show abstract

Section: Discovery Of Vilaprisanmentioning

confidence: 99%

Discovery of Vilaprisan (BAY 1002670): A Highly Potent and Selective Progesterone Receptor Modulator Optimized for Gynecologic Therapies

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Though more reactive, perfluoroalkyllithium and magnesium reagents are comparatively less stable; C 2 F 5 Li, for example, has been reported to have a half-life of 8 hours at −78 • C 114,115 . Perfluoroalkylmagnesium reagents are typically generated at −50 to 0 • C 116 , and consequently are often used under Barbier conditions.…”

Section: Brmentioning

confidence: 99%

Fluorinated Organozinc Reagents

Davis

Burton

2009

Patai's Chemistry of Functional Groups

View full text Add to dashboard Cite

Introduction Fluoroalkenylzinc Reagents Perfluoroaryl Zinc Reagents Fluorinated Allyl and Propargylzinc Reagents Perfluoroalkynylzinc Reagents Perfluoroalkylzinc Reagents Dialkoxyphosphinyldifluoromethylzinc Reagents Carboalkoxydifluoromethylenezinc Reagents

show abstract

“…The compounds described in this study were synthesized by the following methods: Boc-L-amino aldehyde was condensed with perfluoroethyl [15] or perfluoropropyl lithium generated in situ by the addition of methyllithium (complexed with lithium bromide) to the corresponding perfluoroalkyl iodide at -78°C. The resulting Boc-fluoro alcohol was deprotected and coupled to Boc-Phe-His-OH or other dipeptides to give the precursor to the fluoro ketones.…”

Section: Pepsin and Cathepsin D Assaysmentioning

confidence: 99%

Highly potent and specific inhibitors of human renin

et al. 1987

View full text Add to dashboard Cite

We have designed and synthesized a series of small peptides containing a perfluoroalkyl ketone group at the C‐terminal position of the angiotensin I sequence as inhibitors of human renin. From this series of compounds, 8 and 10 showed strong inhibition of human renin (IC50 = 3 × 10−9, 7 × 10−9 M, respectively). Compound 10 did not inhibit pepsin and cathepsin D at 10−4 M. Comparison of the IC50 of compound 8 and compound 11 (8.7 × 10−7 M) demonstrated the marked effect of the perfluoropropyl group on the potency of inhibition on renin, presumably due to the strong electron‐withdrawing effect causing the ketone in 8 to exist predominantly as the hydrate — thus mimicking the tetrahedral transition state during hydrolysis of the scissile Leu10—Val11 amide bond.

show abstract

Pentafluoroethyllithium. Generation and use in synthesis

Cited by 74 publications

References 23 publications

Discovery of Vilaprisan (BAY 1002670): A Highly Potent and Selective Progesterone Receptor Modulator Optimized for Gynecologic Therapies

Discovery of Vilaprisan (BAY 1002670): A Highly Potent and Selective Progesterone Receptor Modulator Optimized for Gynecologic Therapies

Fluorinated Organozinc Reagents

Highly potent and specific inhibitors of human renin

Contact Info

Product

Resources

About