Note : Les revendications sont présentées dans la langue officielle dans laquelle elles ont été soumises.
The embodiments of the invention in which an exclu-
sive property or privilege is claimed are defined as follows:
l. A therapeutic composition comprising in combination as
active ingredients, a pyridine derivative having anti-blood-
platelet-aggregation activity and a derivative having beta-
blocking properties, said combination of active ingredients
having synergistic anti-thrombotic activity;
said pyridine derivative being selected from compounds
having the formula:
<IMG>
(I)
in which:
X represents oxygen or sulfur;
R represents a phenyl or benzoyl group which may carry
one or more substituents selected from halogen atoms and the
straight- or branched-chain lower alkyl groups, the straight-
or branched-chain lower alkoxy groups, the nitro, amino,
sulfonylamino, carboxy, lower alkoxycarbonyl, cyano, phenyl,
hydroxy(lower)alkyl, methylene-dioxy and ethylene-dioxy
groups; an alpha-naphthyl group or a thienyl group;
R1 represents a hydrogen or halogen atom or a hydroxy
group, a straight- or branched-chain lower alkyl group, a
straight- or branched-chain lower alkoxy group, or a phenyl
group;
R' represents a lower alkyl group; and
n is an integer from 1 to 15;
and the symbols R1 may have different meanings in each radical
CHR1 when n is greater than 1;
19
said beta-blocking derivatives being selected from
compounds having the formulas:
<IMG> (II)
and
<IMG> (III)
in which:
R2 is a mono- or polycyclic, carbo- or heterocyclic
radical having at least one ring of aromatic character, and
which is attached to the oxygen atom by a ring carbon atom;
R3 is hydrogen or the acyl radical of an organic
carboxylic acid; and
R4 is a substituted or unsubstituted aliphatic,
cycloaliphatic or araliphatic hydrocarbon radical; and
R5 is hydrogen or a lower alkyl radical;and
the pharmaceutically acceptable inorganic or organic acid
addition salts thereof.
2. The therapeutic composition of claim 1 wherein:
R2 is attached to the oxygen atom by a carbon atom of
an aromatic ring.
3. The therapeutic composition of claim 2 wherein R2 is a
carbocyclic radical selected from the group consisting of
phenyl and partially saturated bicyclic or polycyclic radicals.
4. The therapeutic composition of claim 3 wherein R2 is
selected from the group consisting of the naphthyl, indanyl,
and fluorene radicals.
5. The therapeutic composition of claim 1 wherein R2 is a
heterocyclic radical containing one or more nitrogen, oxygen or
sulfur atoms.
6. The therapeutic composition of claim 5 wherein R2 is a
partially saturated monocyclic or bicyclic heterocyclic radical.
7. The therapeutic composition of claim 6 wherein R2 is
selected from the group consisting of the pyridyl, pyrimidyl,
indolyl and quinolyl radicals.
8. The therapeutic composition of claim 1 wherein R2 is
substituted with a substituted or unsubstituted aliphatic or
cycloaliphatic hydrocarbon radical, an esterified or etherified
hydroxy or mercapto group, or an acyl, carboxy, nitro,
substituted or unsubstituted amino group, or an oxo group.
21
9. The therapeutic composition of claim 1 wherein R3 is a
lower alkanoyl.
10. The therapeutic composition of claim 9 wherein R3 is
benzoyl.
11. The therapeutic composition of claim 1 wherein R4 is
straight- or branch-chained lower alkyl, cycloalkyl or lower
phenyl alkyl groups.
12. The therapeutic composition of claim 1 wherein the
pyridine derivative of formula I is selected from the group
consisting of:
5-(2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine,
(ticlopidine);
5-(3,4,5-trimethoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2-hydroxy-2-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c}
pyridine;
5-p-chlorobenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-p-chlorobenzyl-4,5,6,7-tetrahydro-furo[3,2-c]pyridine;
5-(3,5-dimethoxy-benzyl)3-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(3,4,5-trimethoxy-benzyl)-4,5,6,7-tetrahydro-furo[3,2-c]
pyridine;
5-(3-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-methyl-benzyl)-4,5,6,7-tetrahydro-furo[3,2-c]pyridine;
5-(4-methyl-benzyl)-4,5,6,7-tetrahydro-furo[3,2-c]pyridine;
5-(2-fluoro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3,4-dichloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
22
5-(2-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2-phenyl-ethyl)-4,5,6,7-tetrahydro-furo[3,2 c]pyridine;
5-(1-methyl-2-hydroxy-2-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-methyl-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-methyl-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(4-methyl-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(4-fluoro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2,6-dichloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(2-nitro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(4-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2-p-hydroxyphenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-p-methoxyphenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-p-chloroyphenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-hydroxy-2-o-methoxyphenyl-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-hydroxy-2-m-methoxyphenyl-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(3-o-chloroyphenyl-3-hydroxy-propyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(1-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-hydroxy-3-p-nitrophenyl-propyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(3-hydroxy-3-phenyl-propyl)-4,5,6,7-tetrahydro-thieno[3,2.-c]
pyridine;
5-(2-benzoyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-o-bromobenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
23
5-p-nitrobenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2-p-fluoroyphenyl-2-hydroxy ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2,5 dimethoxy-2-phenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-
thieno[3,2-c]pyridine;
5-(2,3,4-trimethoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-benzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3,4-dimethoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(3-(4-fluoro-benzoyl)-propyl]-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-o-methoxycarbonylbenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-o-carboxybenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-o-methoxycarbonylbenzyl-6-methyl-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(?-naphthyl-methyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-[(5-chloro-2-thienyl)methyl]-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-[2-hydroxy-2-(2-thienyl)-ethyl]-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-o-cyanobenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3,4-methylenedioxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-[2-(4-bis-phenyl)-2-hydroxy-ethyl]-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-o-hydroxy-methylbenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
24
5-benzhydryl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(l-o-chlorophyenyl-butyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(1-o-chlorophyenyl-pentyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(l-o-chlorophyenyl-propyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(l-o-chlorobenzyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c}
pyridine;
5-(l-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
13. The therapeutic composition of claim 1 wherein the
pyridine derivative is 5-(2-chloro benzyl-4,5,6,7-tetrahydro-
thieno [3,2-C] pyridine (ticlopidine) hydrochloride.
14. The therapeutic composition of claim 1 wherein the beta-
blocking derivative of formual II is selected from the group
consisting of:
l-isopropylamino-3-[(1)-naphthyloxy]-2-propanol (propranolol):
(?)l-isopropylamino-3-[4-(2-methoxy-ethyl)-phenoxy]-2-propanol
(metoprolol);
2-[4-(2-hydroxy-3-isopropylamino-propoxy)-phenyl] acetamide
(atenolol);
3'-acetyl-4'-(2-hydroxy-3-isopropylamino-propoxy)-butyranilide
(acebutolol);
1-(4-indolyl-oxy)-3(isopropylamino)-2-propanol (Pindolol):
(-)-l-tert-butylamino)-3-[3-(4-morpholino-1,2,5-thiadiazol-3-yl)
oxy]-2-propanol (timolol);
l-(tert-butylamino)-3-(2-chloro-5-methyl-phenoxy)-2 propanol
(bupranolol);
(?)-5-[3-tert-butylamino)-2-hydroxy-propoxy]3,4-dihydro-2H-
naphthalenone (bunolol);
1-(2'-allyl-phenoxy)-3-isopropylamino-2-propanol (alprenolol):
and 1-(2-allyloxy-phenoxy)-3-isopropylamino-2-propanol
(oxprenolol).
15. The therapeutic composition of claim 1 wherein the beta-
blocking derivative of formula III is selected from the group
consisting of:
2-isopropylamino-1-(1-naphthyl)-ethanol;
2-tert-butylamino-1-(2,5 dimethoxy-phznyl)-ethanol;
1-(3,4-dichlorophenyl)-2-isopropylamino-ethanol;
2-isopropylamino-1-(4-nitro-phenyl)-propanol;
2-isapropylamino-1-(methylsulfonylaminophenyl)-ethanol;
1-(4-carbamoyl-3-hydroxyphenyl)-2-tert-butylamino-ethanol;
and 2-tert-butylamino 1-(1,2,3,4-tetrahydro-5-naphthyl)-ethanol.
16. The therapeutic composition of claim 1 wherein the
pyridine derivative having anti-blood-platelet-aggregation
activity is ticlopidine hydrochloride and the beta-blocking
derivative is selected from the group consisting of propranolol,
acebutolol, metoprolol, and antenolol.
17. A therapeutic composition in unit dosage form comprising
a therapeutically administrable carrier and as active
ingredients, a pyridine derivative having anti-blood-platelet-
aggregation activity and a derivative having beta-blocking
properties, said combination of active ingredients having
synergistic anti-thrombotic activity;
26
in which:
R2 is a mono- or polycyclic, carbo- or heterocyclic
radical having at least one ring of aromatic character, and
which is attached to the oxygen atom by a ring carbon atom;
R3 is hydrogen or the acyl radical of an organic
carboxylic acid; and
R4 is a substituted or unsubstituted aliphatic,
cycloaliphatic or araliphatic hydrocarbon radical; and
R5 is hydrogen or a lower alkyl radical; and the
pharmaceutically acceptable inorganic or organic acid addition
salts thereof.
28
said pyridine derivative being selected from compounds
having the formula:
<IMG> (I)
in which:
X represents oxygen or sulfur;
R represents a phenyl or benzoyl group which may carry
one or more substituents selected from halogen atoms and the
straight- or branched-chain lower alkyl groups, the straight-
or branched-chain lower alkoxy groups, the nitro, amino,
sulfonylamino, carboxy, lower alkoxycarbonyl, cyano, phenyl,
hydroxy(lower)alkyl, methylene-dioxy and ethylene-dioxy
groups; an alpha-naphthyl group or a thienyl group;
R1 represents a hydrogen or halogen atom or a hydroxy
group, a straight- or branched-chain lower alkyl group, a
straight- or branched-chain lower alkoxy group, or a phenyl
group;
R' represents a lower alkyl group; and
n is an integer from l to 15;
and the symbols R1 may have different meanings in each radical
CHR1 when n is greater than 1;
said beta-blocking derivatives being selected from
compounds having the formulas:
<IMG> (II)
and
<IMG> (III)
27
18. The therapeutic dosage unit of claim 16 containing about
0.05 to about 0.2 g of said pyridine derivative and about 0.01
to about 0.15 g of said beta-blocking derivative.
19. The therapeutic dosage unit of claim 17 wherein the
pyridine derivative of formula I is selected from the group
consisting of:
5-(2-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine,
(ticlopidine);
5-(3,4,5-trimethoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(4-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2-hydroxy-2-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-p-chlorobenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-p-chlorobenzyl-4,5,6,7-tetrahydro-furo[3,2-c]pyridine;
5-(3,5-dimethoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(3,4,5-trimethoxy-benzyl)-4,5,6,7-tetrahydro furo[3,2-c]
pyridine;
5-(3-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-methyl-benzyl)-4,5,6,7-tetrahydro-furo[3,2-c]pyridine;
5-(4-methyl-benzyl)-4,5,6,7-tetrahydro-furo[3,2-c]pyridine;
5-(2-fluoro benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3,4-dichloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(2-phenyl-ethyl)-4,5,6,7-tetrahydro thieno[3,2-c]pyridine;
5-(2-phenyl-ethyl)-4,5,6,7-tetrahydro-furo[3,2-c]pyridine;
5-(1-methyl-2-hydroxy-2-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-methyl-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine,
29
5-(3-methyl-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(4-methyl-benzyl)-4,5,6,7-tetrahydro thieno[3,2-c]pyridine;
5-(4-fluoro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2,6-dichloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(2-nitro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(4-hydroxy-benzyl) 4,5,6,7-tetrahydro-thieno[3,2-c]pyridine,
5-(2-p-hydroxyphenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-p-methoxyphenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-p-chloroyphenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-hydroxy-2-o-methoxyphenyl-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2-hydroxy-2-m-methoxyphenyl-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(3-o-chloroyphenyl-3-hydroxy-propyl) -4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(1-phenyl-ethyl3-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-hydroxy-3-p-nitrophenyl-propyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(3-hydroxy-3-phenyl-propyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(2-benzoyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-o-bromobenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-p-nitrobenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-chloro-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3-hydroxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2-p-fluoroyphenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(2,5-dimethoxy-2-phenyl-2-hydroxy-ethyl)-4,5,6,7-tetrahydro-
thieno[3,2-c]pyridine;
5-(2,3,4-trimethoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-benzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(2-methoxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3,4-dimethoxy-benzyl?-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-[3-(4-fluoro-benzoyl)-propyl]-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-o-methoxycarbonylbenzyl-4,596,7-tetrahydro-thieno[3,2-c]
pyridine;
5-o-carboxybenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-o-methoxycarbonylbenzyl-6-m2thyl-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-(?-naphthyl-methyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-[(5-chloro-2-thienyl)methyl] 4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-[2-hydroxy-2-(2-thienyl)-ethyl]-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-o-cyanobenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(3,4-methylenedioxy-benzyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-[2-(4-bis-phenyl)-2-hydroxy-ethyl]-4,5,6,7-tetrahydro-thieno
[3,2-c]pyridine;
5-o-hydroxy-methylbenzyl-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-benzhydryl-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
5-(l-o-chlorophyenyl-butyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
5-(1-o-chlorophyenyl-pentyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyridine;
31
5-(l-o-chlorophyenyl-propyl)-4,5,6,7-tetrahydro-thieno[3,2-c]
pyrldine;
5-(1-o-chlorobenzyl-ethyl)-4,5,6,7 tetrahydro-thieno[3,2-c]
pyridine;
5-(1-phenyl-ethyl)-4,5,6,7-tetrahydro-thieno[3,2-c]pyridine;
20. The theraoeutic dosage unit of claim 17 wherein the
pyridine derivative is 5-(2-chloro-benzyl-4,5,6,7-tetrahydro-
thieno [3,2-C] pyridine (ticlopidine) hydrochloride.
21. The therapeutic dosage unit of claim 17 wherein the beta-
blocking derivative of formual II is selected from the group
consisting of:
l-isopropylamino-3-[(1)-naphthyloxy]-2-propanol (propranolol);
(?)l-isopropylamino-3-[4-(2-methoxy-ethyl)-phenoxy)-2-propanol
(metoprolol);
2-[4-(2-hydroxy-3-isopropylamino-propoxy)-phenyl]acetamide
(atenolol);
3'-acetyl-4l-(2-hydroxy-3-isopropylamino-propoxy)-butyranilide
(acebutolol);
1-(4-indolyl-oxy)-3(isopropylamino)-2-propanol (Pindolol):
1-(tert-butylamino)-3-[3-(4-morpholino-1,2,5-thiadiazol-3-yl)
oxy]-2-propanol (timolol);
l-(tert-butylamino)-3-(2-chloro-5-methyl-phenoxy)-2-propanol
(bupranolol);
(?)-5-[3-tert-butylamino)-2-hydroxy-propoxy]3,4-dihydro-2H-
naphthalenone (bunolol);
1-(2l-allyl-phenoxy)-3-isopropylamino-2-propanol (alprenolol);
and 1-(2-allyloxy-phenoxy)-3 isopropylamino-2-propanol
(oxprenolol).
32
22. The therapeutic dosage unit of claim 17 wherein the beta-
blocking derivative of formula III is selected from the group
consisting of:
2-isopropylamino-1-(1-naphthyl)-ethanol;
2-tert-butylamino-1-(2,5-dlmethoxy-phenyl)-ethanol;
1-(3,4-dichlorophenyl)-2-isopropylamino-ethanol;
2-isopropylamino-1-(4-nitro-phenyl)-propanol;
2-isopropylamino-1-(methylsulfonylaminophenyl)-ethanol;
1-(4-carbamoyl-3-hydroxyphenyl)-2-tert-butylamino-ethanol;
and 2-tert-butylamino-1-(1,2,3,4-tetrahydro-5-naphthyl)-ethanol.
23. The therapeutic dosage unit of claim 17 wherein the
pyridine derivative having anti-blood-platelet-aggregation
activity is ticlopidine hydrochloride and the beta-blocking
derivative is selected from the group consisting of propranolol,
acebutolol, metoprolol, and antenolol.
24. The therapeutic dosage unit of claim 23 containing about
0.05 to about 0.2 g of ticlopidine hydrochloride and about 0.01
to about 0.15 g of one of said beta-blocking derivatives.
33