(+)-Rolipram

(S)-(+)-Rolipram is a PDE4-inhibitor and an anti-inflammatory agent, less potent than its R enantiomer.Target: PDE4B; PDE4DRolipram, a selective inhibitor of the cyclic AMP-specific phosphodiesterase (PDE IV). Rolipram did not inhibit 5-lipoxygenase activity but did inhibit human monocyte production of leukotriene B4 (LTB4, IC50 3.5 microM). Rolipram inhibited arachidonic acid-induced inflammation in the mouse, while the low Km-cyclic-GMP PDE inhibitor. Rolipram had a modest effect on LT

(+)-rolipram is the (S)-enantiomer of rolipram. It is an enantiomer of a (-)-rolipram.

To a solution of 3an(0.2 mmol) in THF (10 mL) was added hydrazine hydrate (0.5 mL) and the solution was stirred for 24 h. After complete consumption of the starting material, the reaction mixture was extracted with dichloromethane and concentrated in vacuum, the residue was dissolved in a mixture of Et3N (0.6 mL) and toluene (3 mL) and the resultant solution heated at 110 °C for 20 h. After cooling to rt, the solvents were evaporated under reduced pressure. The residue was purified by flash chromatography (silica gel, ethyl acetate) to yield colorless crystals (78percent).Thechiral catalyst 0.10 mmol shown in terms of the malonate 5.0 mmol shown interms of 3 - (cyclopentoxy) -4- methoxy phenyl night shown in terms of thechemical formula 2 in the alkyne 1.0 mmol, and the chemical formula 7, and thechemical formula 6 was stirred in the mixed solvent of the saturation sodiumchloride aqueous solution (saturated sodium chloride aqueous solution) 2.0 mLdepartment toluene 0.2 mL of 20 for 24 hours. Thereaction mixture the solvent was removed using the dichloromethane(CH(sub)2(/sub)Cl(sub)2(/sub)) solvent after doing the extraction under thereduced pressure and the product was separated after the stirring end using thecolumn chromatography and the chirality (R) - rolipram precursor was obtained(95percent yield). (R)- , (enantiomeric excess) (CHIRALCEL AD-H, 90:10, :, 210 nm, 1.0 ml/, t()=19.7, t()=42.2, 87percent ee, (R)-form). Themanufactured chirality (R) - rolipram precursor the enantiomeric excess wasmeasured using the high effectiveness liquid chromatography (the CHIRALCELAD-H, 90:10, hexane isopropyl alcohol, 210 nm, 1.0 ml /, T (major product)=19.7 minute, T (by-product) =42.2 minute, 87percent ee, (R) -form).

S-(+)-Rolipram inhibits human monocyte cyclic AMP-specific PDE4 with IC50 of 0.75 μM, has anti-inflammatory and anti-depressant activity in the central nervous system, less potent than its R enantiomer

Molecular Weight:275.34
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:275.15214353
Monoisotopic Mass:275.15214353
Topological Polar Surface Area:47.6
Heavy Atom Count:20
Complexity:341
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes