e.g. Filippa Pettersson or Cancer Res. 75(6) , 1102-12, (2015) or 10.1002/anie.201600521

Synthesis and biological evaluation of ticagrelor derivatives as novel antiplatelet agents

H Zhang, J Liu, L Zhang, L Kong, H Yao…

Index: Bioorganic and Medicinal Chemistry Letters, , vol. 22, # 11 p. 3598 - 3602

Full Text: HTML

Citation Number: 19

Abstract

... Bioorganic & Medicinal Chemistry Letters. ... That is, there are still unmet medical needs for the treatment of ACS and its complications, and novel antiplatelet agents with fast onset of action, less interindividual variability, and low risk of bleeding are desirably needed. ...

N-(((4S,5R)-2,2-dimethyl-5-vinyl-1 ,3-dioxolan-4-yl)methylene)-1-phenylmethanamine oxide Structure

N-(((4S,5R)-2,2...

~%

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

((3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol Structure

((3aR,4R,6R,6aR...

~%

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

D-Lyxofuranose (9CI) Structure

D-Lyxofuranose (9CI)

~%

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

Methyl 2,3-O-isopropylidene-5-O-(p-tolylsulfonyl)-beta-D-ribofuranoside Structure

Methyl 2,3-O-is...

~%

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

D-erythro-Pent-4-enose, 4,5-dideoxy-2,3-O-(1-methylethylidene)- (9CI) Structure

D-erythro-Pent-...

~%

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

(3aS,4S,7R,7aS)-6-benzyl-2,2-dimethyltetrahydro-4H-4,7-methano[1,3]dioxolo[4,5-d][1,2]oxazine Structure

(3aS,4S,7R,7aS)...

~%

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

(3aS,4S,6aR)-4-(iodomethyl)-6-methoxy-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxole Structure

(3aS,4S,6aR)-4-...

~%

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ol Structure

(3aR,4S,6R,6aS)...

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

N-(((4S,5R)-2,2-dimethyl-5-vinyl-1 ,3-dioxolan-4-yl)methylene)-1-phenylmethanamine oxide Structure

N-(((4S,5R)-2,2...

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

((3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol Structure

((3aR,4R,6R,6aR...

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

Methyl 2,3-O-isopropylidene-5-O-(p-tolylsulfonyl)-beta-D-ribofuranoside Structure

Methyl 2,3-O-is...

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

D-erythro-Pent-4-enose, 4,5-dideoxy-2,3-O-(1-methylethylidene)- (9CI) Structure

D-erythro-Pent-...

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

(3aS,4S,7R,7aS)-6-benzyl-2,2-dimethyltetrahydro-4H-4,7-methano[1,3]dioxolo[4,5-d][1,2]oxazine Structure

(3aS,4S,7R,7aS)...

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

D-Lyxofuranose (9CI) Structure

D-Lyxofuranose (9CI)

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

(3aS,4S,6aR)-4-(iodomethyl)-6-methoxy-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxole Structure

(3aS,4S,6aR)-4-...

~%

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

6-Hydroxy-2-(propylsulfanyl)pyrimidin-4(3H)-on Structure

6-Hydroxy-2-(pr...

~%

4,6-dichloro-2-propylsulfanylpyrimidin-5-amine Structure

4,6-dichloro-2-...

4,6-dihydroxy-5-((E)-2-(4-methylphenyl)diazenyl)-2-(propylsulfanyl)pyrimidine Structure

4,6-dihydroxy-5...

~%

4,6-dichloro-2-propylsulfanylpyrimidin-5-amine Structure

4,6-dichloro-2-...

2-[[(3aS,4R,6S,6aR)-4-[7-[[(1R,2S)-2-(3,4-Difluorophenyl)cyclopropyl]amino]-5-(propylthio)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-3-yl]-2,2-dimethyl-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-6-yl]oxy]ethanol Structure

2-[[(3aS,4R,6S,...

~91%

Ticagrelor Structure

(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ol Structure

(3aR,4S,6R,6aS)...

~%

Ticagrelor Structure

Ticagrelor InterMediate1 Structure

Ticagrelor Inte...

~%

Ticagrelor Structure

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-hydroxy-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamicacid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

~%

Ticagrelor Structure

N-[(3aS,4R,6S,6aR)-Tetrahydro-6-(2-hydroxyethoxy)-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-yl]carbamic acid phenylmethyl ester Structure

N-[(3aS,4R,6S,6...

~%

Ticagrelor Structure

1,2-Difluorobenzene Structure

1,2-Difluorobenzene

~%

Ticagrelor Structure

4,6-dichloro-2-propylsulfanylpyrimidin-5-amine Structure

4,6-dichloro-2-...

~%

Ticagrelor Structure

N-(((4S,5R)-2,2-dimethyl-5-vinyl-1 ,3-dioxolan-4-yl)methylene)-1-phenylmethanamine oxide Structure

N-(((4S,5R)-2,2...

~%

Ticagrelor Structure

((3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol Structure

((3aR,4R,6R,6aR...

~%

Ticagrelor Structure

Methyl 2,3-O-isopropylidene-5-O-(p-tolylsulfonyl)-beta-D-ribofuranoside Structure

Methyl 2,3-O-is...

~%

Ticagrelor Structure

D-erythro-Pent-4-enose, 4,5-dideoxy-2,3-O-(1-methylethylidene)- (9CI) Structure

D-erythro-Pent-...

~%

Ticagrelor Structure

(3aS,4S,7R,7aS)-6-benzyl-2,2-dimethyltetrahydro-4H-4,7-methano[1,3]dioxolo[4,5-d][1,2]oxazine Structure

(3aS,4S,7R,7aS)...

~%

Ticagrelor Structure

(3aS,4S,6aR)-4-(iodomethyl)-6-methoxy-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxole Structure

(3aS,4S,6aR)-4-...

~%

Ticagrelor Structure

4,6-dihydroxy-5-((E)-2-(4-methylphenyl)diazenyl)-2-(propylsulfanyl)pyrimidine Structure

4,6-dihydroxy-5...

~%

Ticagrelor Structure

4,6-dichloro-5-((E)-2-(4-methylphenyl)diazenyl)-2-(propylsulfanyl)pyrimidine Structure

4,6-dichloro-5-...

~%

Ticagrelor Structure

(1S)-2-Chloro-1-(3,4-difluorophenyl)ethanol Structure

(1S)-2-Chloro-1...

~%

Ticagrelor Structure

(2S)-2-(3,4-Difluorophenyl)oxirane Structure

(2S)-2-(3,4-Dif...

~%

Ticagrelor Structure

(1R,2R)-Ethyl 2-(3,4-difluorophenyl)cyclopropanecarboxylate Structure

(1R,2R)-Ethyl 2...

~%

Ticagrelor Structure

trans-(1R,2R)-2-(3,4-difluorophenyl)cyclopropanecarbonyl chloride Structure

trans-(1R,2R)-2...

~%

Ticagrelor Structure

(1R,2R)-2-(3,4-difluorophenyl)cyclopropane carboxamide Structure

(1R,2R)-2-(3,4-...

~%

Ticagrelor Structure

D-Lyxofuranose (9CI) Structure

D-Lyxofuranose (9CI)

~%

Ticagrelor Structure

2-Chloro-1-(3,4-difluorophenyl)ethanone Structure

2-Chloro-1-(3,4...

~%

Ticagrelor Structure

((3aR,4R,6R,6aR)-6-Methoxy-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol Structure

((3aR,4R,6R,6aR...

~%

(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ol Structure

(3aR,4S,6R,6aS)...

Methyl 2,3-O-isopropylidene-5-O-(p-tolylsulfonyl)-beta-D-ribofuranoside Structure

Methyl 2,3-O-is...

~%

(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ol Structure

(3aR,4S,6R,6aS)...

(3aS,4S,6aR)-4-(iodomethyl)-6-methoxy-2,2-dimethyl-tetrahydro-2H-furo[3,4-d][1,3]dioxole Structure

(3aS,4S,6aR)-4-...

~%

(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ol Structure

(3aR,4S,6R,6aS)...

D-Lyxofuranose (9CI) Structure

D-Lyxofuranose (9CI)

~%

(3aR,4S,6R,6aS)-6-Aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxol-4-ol Structure

(3aR,4S,6R,6aS)...

From ATP to AZD6140: the discovery of an orally active rever...

[Bioorganic and Medicinal Chemistry Letters, , vol. 17, # 21 p. 6013 - 6018]