11 The Use of Antithrombotic Drugs in Artery Disease

As, Gallus

doi:10.1016/s0308-2261(18)30028-6

Cited by 23 publications

(16 citation statements)

References 237 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After 2 h, the solution was diluted with H2O and extracted with CH2CI2 to leave an oil which was chromatographed on a column of silica gel using a mixture of hexanes and EtOAc (17:3) as eluent to give 7, R = OEt (29.62 g, 61 %). Recrystallization from a mixture of hexanes and CH2CI2 (8:1) gave analytically pure material: mp 71-72 °C; IR (KBr) 1740 (C02Et) cm-1; NMR (CDCla) S 1.26 (3H, t, J = 7 Hz, CO2CH2C/Í3), 3.91 (2H, s, C772C02Et), 4.22 (2H, q,«7 = 7 Hz, OCH2), 7.25-7.45 (6H, m, aromatic ), 7.50-7.75 (4H, m, aromatic H); MS m/z 308 (MH+). Anal.…”

Section: Methodsmentioning

confidence: 99%

“…Elution with a mixture of hexanes and EtOAc NMR (CDCla) 51.19 (3H, t,«7 = 7 Hz, OCH2C773), I. 45 (9H, s, OC(C773)3), 3.44 (2H, overlapping AB q, CJfj-aryl), 4.18 (3H, q, C77C02C772CH3), 4.43 (2H, s, OCH2), 6.72 (1H, dd, «7=7 Hz, J' = 2 Hz, aryl H ortho to O), 6.75 (1H, d, «7 = 2 Hz, aryl H ortho to 0), 6.86 (1H, d, «7= 7 Hz, aryl H para to 0), 7.17 (1H, t, «7= 7 Hz, aryl H meta to 0), 7.25-7.42 (6H, m, aromatic ), 7.50-7.70 (4H, m, aromatic 77); MS m/z 528 (M+). Anal.…”

Section: (E)-and (Z)-ethyl A-[[3-[[(ll-dimethylethoxy)carbonyl]methox...mentioning

confidence: 99%

“…The mixture was stirred for 30 min before being diluted with saturated NH4CI solution and extracted with EtgO to give an oil (1.46 g) which was dissolved in CH3CN (70 mL). Methyl bromoacetate (0.60 g, 3.9 mmol), K2C03 (0.59 g, 4.3 mmol), and KI (catalytic quantity) were added, and the mixture was heated at reflux for 1 h. The mixture was filtered through Celite and concentrated and the residual oil subjected sequentially to column and radial chromatography over silica gel using CHCls as eluent to give (Z)-9a (0.97 g, 56%): IR (film) 1765,1740,1215 cm-1; NMR (CDCls) 1.20 (3H, t, J = 7 Hz, OCH2C773), 3.79 (3H, s, C02C773), 4.39 (2H, q, «7 = 7 Hz, OCT72CH3), 4.62 (2H, s OC772), 6.90 (1H, dd, «7=7 Hz, «7' = 2 Hz, aromatic 77 ortho to O), 6.98 (1H, d, «7 = 2 Hz, aromatic 77 ortho to O), 7.10 (1H, d, «7= 7 Hz, aromatic 77para to O), 7.23 (0.45H, s, C77C13), 7.25-7.45 (7H, m, aromatic 77), 7.55-7.73 (4H, m, aromatic 77), 7.62 (E)-Ethyla-[[3-(2-methoxy-2-oxoethoxy)phenyl]methylene]-4,5-diphenyl-2-oxazoleacetate ((E)•9a) was prepared from (£)-14 (2.88 g, 5.5 mmol) via an analogous procedure to that described for (Z)-14 to afford (E)-9a (2.33 g, 100%): IR (film) 1760,1715,1450 cm-1; NMR (CDC13) 1.27 (3H, t, «7 = 7 Hz, OCH2C773), 3.59 (3H, s, OC773), 4.28 (2H, q, «7 = 7 Hz, OC772CH3), 4.39 (2H, s, OCH2), 5.22 (0.4H, s, C772C12), 6.73 (1H, d, «7 = 2 Hz, aromatic 77 ortho to O), 6.85-6.95 (2H, m, aromatic 77 ortho and para to O), 7.19 (1H, t, «7 = 7 Hz, aromatic 77 meta to O), 7.20-7.40 (6H, m, aromatic 77), 7.53 (2H, m, aromatic 77), 7.68 (2H, m, aromatic 77), 8.03 (1H, s, olefinic 77); MS m/z 484 (MH+). Anal.…”

Section: Ethyla-[[3-(2-hydroxy-2-oxoethoxy)phenyl]methyl]-45diphenyl-...mentioning

confidence: 99%

“…The solvent was removed the residue diluted with 1 N HC1 and extracted with CH2C12 to give an oil. NMR (CDCls) & 1.23 (3H, t,J=7 Hz, OCH2Ctfa), 1.27 (3H, t,J=7 Hz, OCH2CH3), 3.30-3.60 (2H, m, CHüAr), 3.90 (1H, ddd, J -22 Hz, J' = 10 Hz, J" = 5 Hz, CflP(0)(OEt)2), 4.00-4.20 (4H, m, OCff2), 6.61 (2H, m, aromatic H ortho and para to OH), 6.83 (1H, aromatic H ortho to OH), 7.01 (1H, t, J = 8 Hz, aromatic H meta to OH), 7.28 (6H, m, aromatic H), 7.40-7.60 (4H, m, aromatic H), 7.92 (1H, s, OH); MS m/z 478 (MH+). Anal.…”

Section: Ethyla-[[3-(2-hydroxy-2-oxoethoxy)phenyl]methyl]-45diphenyl-...mentioning

confidence: 99%

“…The residue was chromatographed on a column of silica gel using Et^O/hexane (1:1) as eluent to furnish 30a (15.88 g, 95%) as an oil. IR (film) 1765,1740 cm-1; NMR (CDCla) 2.16 (3H, s, SCHa), 3.36 (2H, ABX dq, Jab = 14 Hz, J'ax = 8.3 Hz, JBX * 7.3 Hz, ArC Hi), 3.75 (3H, s, C02Ctf3), 4.17 (1H, t,J= 7.5, CH&CH), 4.55 (2H, s, OCff2), 6.75 (1H, dd, J = 7 Hz, J'= 2 Hz, aromatic Hortho to O), 6.80 (1H, d, J = 2 Hz, aromatic Hortho to 0), 6.89 (1H, d, J = 7 Hz, aromatic H para to 0), 7.19 (1H, t, J = 7 Hz, aromatic H meta to OH), 7.25-7.40 (6H, m, aromatic ), 7.50- NMR (CDCla) 2.15 (3H, s, SCff3), 3.34 (2H, ABX dq, Jab = 14 Hz, Jax = 8.6 Hz, JBx = 7.3 Hz, ArCH2), 4.39 (1H, ABX dd, Jax + Jbx = 15.9 Hz, CHaSCH), 4.57 (2H, s, OCH2), 6.76 (1H, dd, J = 7 Hz, J' = 2 Hz, aromatic H ortho to 0), 6.80-6.90 (2H, m, aromatic H ortho and para to O), 7.16 (1H, t, J 7 Hz, aromatic H meta to OH), 7.25-7.40 (6H, m, aromatic H), 7.50-7.70 (4H, m, aromatic ), 8.18 (30b). A solution of 30a (6.68 g, 14.5 mmol) in MeOH (200 mL) was cooled to -10 °C and a solution of Oxone (10.36 g, 16.9 mmol) in H20 (100 mL) added in one portion.…”

Section: Ethyla-[[3-(2-hydroxy-2-oxoethoxy)phenyl]methyl]-45diphenyl-...mentioning

confidence: 99%

See 4 more Smart Citations

Nonprostanoid prostacyclin mimetics. 4. Derivatives of 2-[3-[2-(4,5-diphenyl-2-oxazolyl)ethyl]phenoxy]acetic acid substituted .alpha. to the oxazole ring

Meanwell

Mj²,

Jj³

et al. 1993

J. Med. Chem.

View full text Add to dashboard Cite

The 4,5-diphenyloxazole derivatives 2-4 were previously identified as nonprostanoid prostacyclin (PGI2) mimetics. A series of derivatives of 2-4 bearing substitutents at the carbon atom alpha to the oxazole ring were synthesized and evaluated as inhibitors of ADP-induced aggregation of human platelets in vitro. In the unsaturated series, the alpha-carbethoxy derivative 10a, evaluated as an equal mixture of geometrical isomers, inhibited platelet aggregation with an IC50 of 0.36 microM. Evaluation of the individual methyl ester derivatives (E)-9a and (Z)-9a revealed that (E)-9a was 10-fold more potent than (Z)-9a. In the saturated series, the alpha-carbomethoxy-substituted compound 12a inhibited platelet aggregation with an IC50 of 0.08 microM, 15-fold more potent than the unsubstituted prototype 2. The potency of 12a was found to be sensitive to variation of the methoxy moiety. The ethyl (12b) and isopropyl (12d) esters were less effective as were the acid 12e and a series of amides (12f-h). Other substituents introduced at this site of the pharmacophore included P(O)(OEt)2 (25), SCH3 (31a), S(O)CH3 (31b), SO2CH3 (31c), isopropyl (31d), phenyl (31f), and CH2OH (31i). However, none were significantly more potent inhibitors of platelet function than the parent compound 2. The results indicate the presence of a pocket in the PGI2 receptor protein that preferentially recognizes small, polar but uncharged substituents. The structure-activity correlates are suggestive of a hydrogen-bond interaction between a donor moiety on the PGI2 receptor and the methoxycarbonyl functionality of 12a that is sensitive to both the size of the substituent and its stereochemical presentation in this structural class of PGI2 mimetic. The ethyl ester 12b dose-dependently displaced [3H]iloprost from human platelet membranes and stimulated adenylate cyclase. However, the maximal stimulation was less than that recorded for iloprost, indicating that 12b functions as a partial agonist at the PGI2 receptor.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: (E)-and (Z)-ethyl A-[[3-[[(ll-dimethylethoxy)carbonyl]methox...mentioning

confidence: 99%