US 2019/0055260 A1 · OPTICALLY ACTIVE 2-HYDROXY TETRAHYDROTHIENOPYRIDINE DERIVATIVES, PREPARATION METHOD AND USE IN MANUFACTURE OF MEDICAMENT THEREOF

Abstract

Optically active 2-hydroxytetrahydrothienopyridine derivatives represented by Formula I and pharmaceutically acceptable salts, preparation method and use in the manufacture of a medicament thereof are disclosed. The pharmacodynamic experiment results show that the present compounds of Formula I are useful for inhibiting platelet aggregation. The pharmacokinetic experiment results show that the present compound of Formula I can be converted in vivo into pharmacologically active metabolites and are therefore useful for inhibiting platelet aggregation. Therefore, the present compounds are useful for the manufacture of a medicament for preventing or treating thrombosis and embolism related diseases.

Claims9

Dependent claims

1-4. (canceled)

A compound or a pharmaceutically acceptable salt or hydrate thereof, wherein the compound is

(S)-methyl 2-(2-propanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-3;
(S)-methyl 2-(2-butanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-4;
(S)-methyl 2-(2-(2-acetoxybenzoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-5;
(S)-methyl 2-(2-pivaloyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-7;
(S)-methyl 2-(2-(2,2-dimethylbutanoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-8;
(S)-methyl 2-(2-cinnamoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-9;
(S)-methyl 2-(2-(4-methoxybenzoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-11;
(S)-methyl 2-(2-phenylacetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-12;
(S)-methyl 2-(2-(phenoxyacetoxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-13;
(S)-methyl 2-(2-(ethoxycarbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-14;
(S)-methyl 2-(2-(isobutoxycarbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-15;
(S)-methyl 2-(2-(isopropoxycarbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-16;
(S)-methyl 2-(2-(benzyloxycarbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-17;
(S)-methyl 2-(2-(N,N-dimethylcarbamoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-18;
(S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)-acetate I-19;
(S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(4-chlorophenyl)-acetate I-20;
(S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-phenyl-acetate I-21;
(S)-methyl 2-(2-(pyrrolidine-1-carbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-22;
(S)-methyl 2-(2-(methoxycarbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-23;
(S)-methyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-bromophenyl)-acetate I-24;
(S)-ethyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)-acetate I-25;
(S)-ethyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-26;
(S)-ethyl 2-(2-acetoxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-bromophenyl)-acetate I-27;
(S)-methyl 2-(2-propanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)-acetate I-28;
(S)-methyl 2-(2-propanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-bromophenyl)-acetate I-29;
(S)-ethyl 2-(2-propanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)-acetate I-30;
(S)-ethyl 2-(2-propanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-31;
(S)-ethyl 2-(2-propanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-bromophenyl)-acetate I-32;
(S)-methyl 2-(2-butanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)-acetate I-33;
(S)-methyl 2-(2-butanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-bromophenyl)-acetate I-34;
(S)-ethyl 2-(2-butanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)-acetate I-35;
(S)-ethyl 2-(2-butanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-36;
(S)-ethyl 2-(2-butanoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-bromophenyl)-acetate I-37;
(S)-ethyl 2-(2-pivaloyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-38;
(S)-ethyl 2-(2-(2,2-dimethylbutanoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-39;
(S)-methyl 2-(2-feruloyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-40;
(S)-methyl 2-(2-benzoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-fluorophenyl)-acetate I-41;
(S)-methyl 2-(2-nicotinoyloxy-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(4-chlorophenyl)-acetate I-42;
(S)-methyl 2-(2-(2-hydroxybenzoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-43;
(S)-methyl 2-(2-(t-butoxycarbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-44;
(S)-methyl 2-(2-(N,N-diethylcarbamoyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-45;
and
(S)-methyl 2-(2-(piperdine-1-carbonyloxy)-6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)-2-(2-chlorophenyl)-acetate I-46.

40 more elements

Dependencies are inferred from the claim text.

Facts

Application

16/008,436Filed 14 Jun 2018

Priority

CN 201010104091.52 Feb 2010

Published

21 Feb 2019

Term ends

Not estimatedThe source records don’t support an estimate.

Classification11 codes

C07D 495/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/4365
Ortho- or peri-condensed with heterocyclic ring systems: the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
A61P 7/00
Drugs for disorders of the blood or the extracellular fluid
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Family

Application13/576,534Continuation · filed 18 Sep 2012

Application14/322,939Continuation · filed 3 Jul 2014

Application15/275,967Continuation · filed 26 Sep 2016

Application16/008,436Continuation

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From the US filing history. Foreign family members aren’t listed.

Optically active 2-hydroxy tetrahydrothienopyridine derivatives, preparation method and use in manufacture of medicament thereof

Life of this patent

Optically active 2-hydroxy tetrahydrothienopyridine derivatives, preparation method and use in manufacture of medicament thereof

Life of this patent

Abstract

Claims9