US 6,783,774 B1 · Substance that stop any kind of bleeding within one second for medical, surgical, postsurgical and dental uses

Abstract

There is disclosed a method for stopping bleeding and forming black blood coagulation on contact, comprising administering powdered L-threo-hex-2-enono-1,4-lactone thereof to a bleeding site in an amount of 0.1568 grams for every milliliter of blood. This includes cancer, liver diseases and hemophiliac bleeding in patients or animals in whom the thrombocytopenia or coagulation factors disorders result. Accordingly, the said mechanism of action of powdered L-threo-hex-2-enono-1,4-lactone in the formation of blood coagulation on contact is the unique common pathway for all blood coagulations, which overturns the mechanisms of intrinsic and extrinsic pathways for blood coagulation cascade being the unique pathways for blood coagulation in which the coagulation factors 1, 2, 5, 7, 8, 9, 10 and platelet factor 3 are essential for the pathways.

Claims20

Dependent claims

A method for stopping bleeding at a bleeding site of a human or an animal in body tissue caused by pathological changes, trauma or surgery, comprising administering topically to the bleeding site powdered D,L-threo-hex-2-enono-1,4-lactone and excipients.

A method of stopping bleeding which comprises administering an effective amount of D,L-threo-hex-2-enono-1,4-lactone derivative, D,L-threo-hex-2-enono-1,4-lactone-2-R1-5-R2-R3, wherein R1 is of the formula —CH2—R wherein R is a C5-22 straight-chain or branched alkyl;

a C1-10 straight-chain or branched-chain alkyl group having 1 to 3 substituents selected from the group consisting of:
(1) C1-6 alkoxycarbonyl, (2) phenyl or naphthyl optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (3) benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (4) phenylcarbonyloxy or naphthylcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (5) benzylcarbonyloxy or phenethylcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxy and benzyloxy, (6) 2,3,5-trimethyl-1,4-benzoquinonyl, (7)2,3-dimethoxy-5-methyl-1,4-benzoquinonyl and (8) 2-methyl-1,4-napthoquinonyl;
a C2-20 alkenyl group having one to three substituents selected from the group consisting of phenyl, naththyl, benzyl or phenethyl, 3-pyridyl, thienyl and furyl;
a phenyl, naphthyl, benzyl, phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C-5 alkyl, methoxy, methylenedioxy and hydroxyl;
a C1-9 acyl group selected from the group consisting of:
formyl, acetyl, propionyl, n-butyryl, isobutyryl, benzoyl, morpholino-carbonyl, C1-3 alkoxycarbonyl prrolidinocarbonyl, 1-3 alkoxycarbonyl, phenylcarbonyl or naphthylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy, benzylcarbonyl or phenethylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
benzylcarbonyl or phenethycarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
a phenyloxy, naphthyloxy, benzyloxy or phenethyloxy optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
R2 is hydrogen or hydroxy, and R3 is hydogen, or acyl;
or R2 and R3 may together form an O,O-isopropylidene residue;
or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, vehicle or diluent therefor;
wherein R3 is acyl.

16 more elements

A method of stopping bleeding which comprises administering an effective amount of D,L-threo-hex-2-enono-1,4-lactone derivative, D,L-threo-hex-2-enono-1,4-lactone-2-R1-5-R2-6-R3 wherein R1 is of the formula —CH2—R, wherein R is a C5-22 straight-chain or branched alkyl;

a C1-10 straight-chain or branched-chain alky group having one to three substituents selected from the group consisting of:
(1) C1-6 alkoxycarbonyl, (2) phenyl or naphthyl optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (3) benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (4) phenylcarbonyloxy or naphthycarbonyloxy optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (5) benzylcarbonyloxy or phenethylcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxy and benzyloxy, (6) 2,3,5-trimethyl-1,4-benzoquinonyl, (7)2,3-dimethoxy-5-methyl-1,4-benzoquinonyl and (8) 2-methyl-1,4-napthoquinonyl;
a C2-20 alkenyl group having one to three substituents selected from the group consisting of phenyl, naththyl, benzyl or phenethyl, 3-pyridyl, thienyl and furyl;
a phenyl, naphthyl, benzyl, phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, methoxy, methylenedioxy and hydroxyl;
a C1-9 acyl group selected from the group consisting of:
formyl, acetyl, propionyl, n-butyryl, isobutyryl, benzoyl, morpholino-carbonyl, C1-3 alkoxycarbonyl prrolidinocarbonyl, 1-3 alkoxycarbonyl, phenylcarbonyl or naphthylcarbonyl optionally substituted with one to three substituents selected from the group consisting of hydroxyl, C1-5 alkyl and C1-3 alkoxy, benzylcarbonyl or phenethylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
benzylcarbonyl or phenethycarbonyl optionally substituted with one to three substituents selected from the group consisting of hydroxyl, C1-5 alkyl and C1-3 alkoxy;
a phenyloxy, naphthyloxy, benzyloxy or phenethyloxy optionally substituted with one to three substituents selected from the group consisting of hydroxyl, C1-5 alkyl and C1-3 alkoxy;
R2 is hydrogen or hydroxy;
and R3 is hydogen, or acyl;
or R2 and R3 may together form an O,O-isopropylidene residue, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, vehicle or diluent therefor;
wherein, R1 is —(CH2)10COOCH3, R2 is hydroxyl and R3 is hydrogen.

13 more elements

A method of stopping bleeding which comprises administering to the bleeding site an effective amount of D,L-threo-hex-2-enono-1,4-lactone derivative, D,L-threo-hex-2-enono-1,4-lactone-2-R1-5-R2-6-R3 to stop bleeding on contact, wherein R1 is of the formula —CH2—R, wherein R is a C5-22 straight-chain or branched alkyl;

a C1-10 straight-chain or branched-chain alky group having one to three substituents selected from the group consisting of:
(1) C1-6 alkoxycarbonyl, (2) phenyl or naphthyl optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (3) benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (4) phenylcarbonyloxy or naphthycarbonyloxy optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (5) benzylcarbonyloxy or phenethylcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxy and benzyloxy, (6) 2,3,5-trimethyl-1,4-benzoquinonyl, (7)2,3-dimethoxy-5-methyl-1,4-benzoquinonyl and (8) 2-methyl-1,4-napthoquinonyl;
a C2-20 alkenyl group having one to three substituents selected from the group consisting of phenyl, naththyl, benzyl or phenethyl, 3-pyridyl, thienyl and furyl;
phenyl, naphthyl, benzyl, phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, methoxy, methylenedioxy and hydroxyl;
a C1-9 acyl group selected from the group consisting of:
formyl, acetyl, propionyl, n-butyryl, isobutyryl, benzoyl, morpholino-carbonyl, C1-3 alkoxycarbonyl prrolidinocarbonyl, 1-3 alkoxycarbonyl, phenylcarbonyl or naphthylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy, benzylcarbonyl or phenethylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
benzylcarbonyl or phenethycarbonyl optionally substituted with one to three substituents selected from the group consisting of hydroxyl, C1-5 alkyl and C1-3 alkoxy;
a phenyloxy, naphthyloxy, benzyloxy or phenethyloxy optionally substituted with one to three substituents selected from the group consisting of hydroxyl, C1-5 alkyl and C1-3 alkoxy;
R2 is hydrogen or hydroxy;
and R3 is hydogen, or acyl;
or R2 and R3 may together form an O,O-isopropylidene residue;
or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, vehicle or diluent therefor;
wherein R1 is —(CH2)17CH3, R2 is hydroxyl and R3 is nicotynoyl.

15 more elements

A method of stopping bleeding which comprises administering to the bleeding site an effective amount of D,L-threo-hex-2-enono-1,4-lactone-2-R1-5-R2-6-R3, wherein R1 is of the formula —CH2—R, wherein R is C5-22 straight chain or branched alkyl;

a C1-10 straight chain or branched chain alkyl group having one to three substituents selected from the group consisting of:
(1) C1-6 alkoxycarbonyl, (2) phenyl or naphthyl optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (3) benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (4) phenylcarbonyloxy or naphthcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (5) benzylcarbonyloxy or phenethycarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (6) 2,3,5-trimethyl-1,4-benzoquinonyl, (7) 2,3-dimethoxy-5-methyl-1,4-benzoquinoyl and (8) 2-methyl-1,4-naphthquinonyl;
a C2-20 alkenyl group having one to three substituents selected from phenyl, naphthyl, benzyl, phenethyl, 3-pyridyl, thienyl and furyl;
a phenyl, napthyl, benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, methoxy, methyleneioxy and hydroxyl;
a C1-9 acyl group selected from the group consisting of formyl, acetyl propionyl, n-butyry, isobutyryl, benzoyl, morpholino-carbonyl,C1-3 alkoxycarbonylpyrrolininocarbonyl, C1-3 alkoxycarbonyl, phenylcarbonyl or naphthylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl C1-5 alkyl and C1-3 alkoxy, benzylcarbonyl or phenethylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
a phenyloxy, naphthloxy, benzyloxy or phenethyloxy optionally substituted wih one to thre substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
R2 is hydrogen or hydroxy;
and
R3 is hydrogen, or acyl;
or R2 and R3 may together form an O,O-isopropylidene residue;
or pharmaceutically acceptable salt thereof.

15 more elements

A method of stopping bleeding which comprises administering an effective amount of D,L-threo-hex-2-enono-1,4-lactone derivative, D,L-threo-hex-2-enono-1,4-lactone-2-R1-5-R2-6-R3, wherein R1 is of the formula —CH2—R, wherein R is a C5-22 straight-chain or branched alkyl;

a C1-10 straight-chain or branched-chain alky group having one to three substituents selected from the group consisting of:
(1) C1-6 alkoxycarbonyl, (2) phenyl or naphthyl optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (3) benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (4) phenylcarbonyloxy or naphthycarbonyloxy optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (5) benzylcarbonyloxy or phenethylcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxy and benzyloxy, (6) 2,3,5-trimethyl-1,4-benzoquinonyl, (7)2,3-dimethoxy-5-methyl-1,4-benzoquinonyl and (8) 2-methyl-1,4-napthoquinonyl;
a C2-20 alkenyl group having one to three substituents selected from the group consisting of phenyl, naththyl, benzyl or phenethyl, 3-pyridyl, thienyl and furyl;
a phenyl, naphthyl, benzyl, phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, methoxy, methylenedioxy and hydroxyl;
a C1-9 acyl group selected from the group consisting of:
formyl, acetyl, propionyl, n-butyryl, isobutyryl, benzoyl, morpholinocarbonyl, C1-3 alkoxycarbonyl prrolidinocarbonyl, 1-3 alkoxycarbonyl, phenylcarbonyl or naphthylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy, benzylcarbonyl or phenethylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
benzylcarbonyl or phenethycarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
a phenyloxy, naphthyloxy, benzyloxy or phenethyloxy optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
R2 is hydrogen or hydroxy;
and R3 is hydogen, or acyl;
or R2 and R3 may together form an O,O-isopropylidene residue;
or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, vehicle or diluent therefor, wherein R1 is phenyloxy, naphthyloxy, benzyloxy, or phenethyloxy group which may have one to three substituent(s), the substituent being selected from the group consisting of:
hydroxyl group, C1-5 alkyl group and C1-3 alkoxy group;
wherein R1 is straight chain alkyl having 9 to 20 carbon atoms.

18 more elements

A method of stopping bleeding which comprises administering to the bleeding site an effective amount of D,L-threo-hex-2-enono-1,4-lactone derivative, D,L-threo-hex-2-enono-1,4-lactone-2-R1-5-R2-6-R3, wherein R1 is of the formula —CH2—R, wherein R is a C5-22 straight-chain or branched alkyl;

a C1-10 straight-chain or branched-chain alky group having one to three substituents selected from the group consisting of:
(1) C1-6 alkoxycarbonyl, (2) phenyl or naphthyl optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (3) benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (4) phenylcarbonyloxy or naphthycarbonyloxy optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (5) benzylcarbonyloxy or phenethylcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxy and benzyloxy, (6) 2,3,5-trimethyl-1,4-benzoquinonyl, (7)2,3-dimethoxy-5-methyl-1,4-benzoquinonyl and (8) 2-methyl-1,4-napthoquinonyl;
a C2-20 alkenyl group having one to three substituents selected from the group consisting of phenyl, naththyl, benzyl or phenethyl, 3-pyridyl, thienyl and furyl;
a phenyl, naphthyl, benzyl, phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, methoxy, methylenedioxy and hydroxyl;
a C1-9 acyl group selected from the group consisting of:
formyl, acetyl, propionyl, n-butyryl, isobutyryl, benzoyl, morpholino-carbonyl, C1-3 alkoxycarbonyl prrolidinocarbonyl, 1-3 alkoxycarbonyl, phenylcarbonyl or napbthylcarbonyl optionally substituted with one to three substituents selected from the group consisting of hydroxyl, C1-5 alkyl and C1-3 alkoxy, benzylcarbonyl or phenethylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
benzylcarbonyl or phenethycarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
a phenyloxy, naphthyloxy, benzyloxy or phenethyloxy optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
R2 is hydrogen or hydroxy;
and R3 is hydogen, or acyl;
or R2 and R3 may together form an O,O-isopropylidene residue, or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, vehicle or diluent therefor;
wherein R1 is phenyloxy, naphthyloxy, benzyloxy, or phenenethyloxy group which may have one to three-substituent(s), the substituent being selected from the group consisting of:
C1-5 alkyl group and C1-3 alkoxy group wherein R2 is hydroxyl.

16 more elements

A method of stopping bleeding which comprises administering to the bleeding site an effective amount of D,L-threo-hex-2-enono-1,4-lactone derivative, D,L-threo-hex-2-enono-1,4-lactone-2-R1-5-R2-6-R3, wherein R1 is of the formula —CH2—R, wherein R is a C5-22 straight-chain or branched alkyl;

a C1-10 straight-chain or branched-chain alky group having one to three substituents selected from the group consisting of:
(1) C1-6 alkoxycarbonyl, (2) phenyl or naphthyl optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (3) benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (4) phenylcarbonyloxy or naphthycarbonyloxy optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (5) benzylcarbonyloxy or phenethylcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxy and benzyloxy, (6) 2,3,5-trimethyl-1,4-benzoquinonyl, (7)2,3-dimethoxy-5-methyl-1,4-benzoquinonyl and (8) 2-methyl-1,4-napthoquinonyl;
a C2-20 alkenyl group having one to three substituents selected from the group consisting of phenyl, naththyl, benzyl or phenethyl, 3-pyridyl, thienyl and furyl;
a phenyl, naphthyl, benzyl, phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, methoxy, methylenedioxy and hydroxyl;
a C1-9 acyl group selected from the group consisting of:
formyl, acetyl, propionyl, n-butyryl, isobutyryl, benzoyl, morpholino-carbonyl, C1-3 alkoxycarbonyl prrolidinocarbonyl, 1-3 alkoxycarbonyl, phenylcarbonyl or naphthylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy, benzylcarbonyl or phenethylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
benzylcarbonyl or phenethycarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
a phenyloxy, naphthyloxy, benzyloxy or phenethyloxy optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
R2 is hydrogen or hydroxy;
and R3 is hydogen, or acyl;
or R2 and R3 may together form an O,O-isopropylidene residue;
or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, vehicle or diluent therefor;
wherein R1 is phenyloxy, naphthyloxy, benzyloxy, or phenenethyloxy group which may have one to three substituent(s), the substituent being selected from the group consisting of:
C1-5 alkyl group and C1-3 alkoxy group;
wherein R3 is hydrogen.

19 more elements

A method of stopping bleeding which comprises administering to the bleeding site an effective amount of D,L-threo-hex-2-enono-1,4-lactone derivative, D,L-threo-hex-2-enono-1,4-lactone-2-R1-5-R2-R3, wherein R1 is of the formula —CH2—R, wherein R is a C5-22 straight-chain or branched alkyl;

a C1-10 straight-chain or branched-chain alky group having one to three substituents selected from the group consisting of:
(1) C1-6 alkoxycarbonyl, (2) phenyl or naphthyl optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (3) benzyl or phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (4) phenylcarbonyloxy or naphthycarbonyloxy optionally substituted with one to three substituents selected from the group consisting of C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxyl and benzyloxy, (5) benzylcarbonyloxy or phenethylcarbonyloxy optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, C1-3 alkoxy, halogen, nitro, amino, oxo, hydroxy and benzyloxy, (6) 2,3,5-trimethyl-1,4-benzoquinonyl, (7)2,3-dimethoxy-5-methyl-1,4-benzoquinonyl and (8) 2-methyl-1,4-napthoquinonyl;
a C2-20 alkenyl group having one to three substituents selected from the group consisting of phenyl, naththyl, benzyl or phenethyl, 3-pyridyl, thienyl and furyl;
a phenyl, naphthyl, benzyl, phenethyl optionally substituted with one to three substituents selected from the group consisting of:
C1-5 alkyl, methoxy, methylenedioxy and hydroxyl;
a C1-9 acyl group selected from the group consisting of:
formyl, acetyl, propionyl, n-butyryl, isobutyryl, benzoyl, morpholino-carbonyl, C1-3 alkoxycarbonyl prrolidinocarbonyl, 1-3 alkoxycarbonyl, phenylcarbonyl or naphthylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy, benzylcarbonyl or phenethylcarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
benzylcarbonyl or phenethycarbonyl optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
a phenyloxy, naphthyloxy, benzyloxy or phenethyloxy optionally substituted with one to three substituents selected from the group consisting of:
hydroxyl, C1-5 alkyl and C1-3 alkoxy;
R2 is hydrogen or hydroxy;
and R3 is hydogen, or acyl;
or R2 and R3 may together form an O,O-isopropylidene residue;
or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, vehicle or diluent therefor;
wherein R1 is phenyloxy, naphthyloxy, benzyloxy, or phenenethyloxy group which may have one to three substituent(s), the substituent being selected from the group consisting of:
C1-5 alkyl group and C1-3 alkoxy group, wherein R3 and hydroxyl or R2 form O,O-isopropylidene residue.