Hydroperylene derivatives

Details Hydroperylene derivatives Hydroperylene derivatives

2002-11-21

2004-01-06

Trinh, Ba K. (Department: 1625)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C549S543000

Reexamination Certificate

active

06673834

ABSTRACT:

SUMMARY OF THE INVENTION
The invention relates to hydroperylene derivatives which are formed by the fungus, DSM 14452, during fermentation, or are subsequently derivatized, to processes for preparing them and to their use as pharmaceuticals and inhibitors of blood platelets, as well as to sid novel fungus itself.
BACKGROUND OF THE INVENTION
Hydroperylene derivatives, such as hexahydroperylene derivatives or octahydroperylene derivatives, are formed by various microorganisms. Examples of known hydroperylene derivatives are:
Altertoxins I, II and III (M. E. Stark et al. J. Nat. Prod. 49, 866-871, 1986),
Alteichin (D. Robeson et al. Experientia, 40, 1248-1250, 1984),
the Alterlosins (A. Stierle et al. J. Nat. Prod. 52, 42-47, 1989) and
Alterperylenol from Alternaria species (T. Okuno et al. Tetrahedron Lett. 24, 5653-5656, 1983);
Stemphyltoxins and Stemphypyrenol, which are from cultures of Stemphylium botryosum (A. Arnone et al. J. Chem. Soc. Perkin Trans.1, 1986, 525-530).
The altertoxins and the stemphyltoxins are phytotoxins, which, as a result of their mutagenic effect, can also diminish the value of human foodstuffs. They have herefore been thoroughly described in more than 70 publications (T. J. Schrader et al. Teratog. Carcinog., Mutagen., 21, 261-274, 2001). The dangers which emanate from the altertoxins and stemphyltoxins are naturally dealt with in this literature, including the wide distribution, and the cancer-causing effect, of these compounds, which contain epoxides (oxiranes). In addition to this, alterperylenol has been reported to have a weak telomerase-inhibiting effect (K-I. Togashi et al. Oncol. Res. 10, 449-453, 1998); however, at 30 &mgr;M, the IC
50
value, which is characteristic for inhibition of the enzyme, is low.
Thromboembolic diseases are the most frequent cause of death, particularly in the western industrial nations. An effective prophylaxis and therapy for these diseases is therefore of exceptional importance. A thrombus is understood as being a blood clot which has been formed intravitally and intravascularly. Thrombi are formed following thrombocyte aggregation in arteries, in particular. Damage to the blood vessel wall, retarded blood flow and accelerated clotting all favor thrombus formation. The thrombocytes (blood platelets) are disc-shaped, anucleate blood cells which ensure hemostasis and blood coagulation when injury occurs. Thrombocytes bring about hemostasis by means of aggregation in a complicated process; thrombocyte aggregation is consequently an essential process for homeotherms. Hypofunction of the thrombocytes leads to severe hemorrhages, even in the case of relatively small injuries; on the other hand, an increased tendency towards coagulation increases the danger of thrombosis and embolism. Since platelet hyperfunction, in particular, frequently has fatal consequences, several substances have already been employed as inhibitors of thrombocyte aggregation. Those which are well known include acetylsalicylic acid (Aspirin®), ticlopidine (Tiklyd®) and the related clopidogrel; however, because of side-effects, the use of all these preparations is restricted. For this reason, there is a great need for inhibitors of intracellular platelet activation, which can be used for the therapy and long-term prophylaxis of arterial thromboembolic events. Agents of this nature can be employed, for example, in connection with myocardial infarction, in connection with unstable angina or in connection with strokes.
DETAILED DESCRIPTION OF THE INVENTION
In the endeavor to find effective compounds for preventing or treating blood coagulation diseases, it has now been found that thioperylenol, which is formed by the fungal strain DSM 14452, and other hydroperylene derivatives, are able to effectively inhibit blood platelet aggregation.
The invention, therefore, relates to a compound of formula I
including all stereoisomeric forms of said compound of formula I, mixtures of said forms and compounds in any ratio, and physiologically tolerated salts thereof, wherein:
R1, R2, R3, R4, R5, R6, R7, R8, R10 and R11 are independently selected from the group consisting of
hydrogen;
(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of:
—OH; ═O; —O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: —CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; —O—(C
2
-C
6
)-alkenyl, in which alkenyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of:
—CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; —O—(C
2
-C
6
)-alkynyl, in which alkynyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: —CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; -aryl, in which aryl is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: halogen; —(C
1
-C
4
)-alkyl, in which alkyl is a straight or branched chain; —O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; —OH and —(C
1
-C
4
)-alkyl, in which alkyl is a straight or branched chain and is substituted by one, two or three substituents selected from the group consisting of halogen; —C(O)—OH; —C(O)—O—NH
2
; —C(O)—O—(C
1
-C
4
)-alkyl, in which alkyl is a straight or branched chain; —NH—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: —CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; —NH—(C
2
-C
6
)-alkenyl, in which alkenyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: —CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; —NH—(C
2
-C
6
)-alkynyl, in which alkynyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: —CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; —NH
2
and halogen;
(C
2
-C
6
)-alkenyl, in which alkenyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of:
—OH; ═O; —O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: —CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; —O—(C
2
-C
6
)-alkenyl, in which alkenyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: —CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; —O—(C
2
-C
6
)-alkynyl, in which alkynyl is a straight or branched chain and is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: —CN; —NH
2
; ═N—OH and ═N—O—(C
1
-C
6
)-alkyl, in which alkyl is a straight or branched chain; -aryl, in which aryl is unsubstituted or substituted by one, two or three substituents independently selected from the group consisting of: halogen; —(C
1
-C
4
)-alkyl, in which alkyl is a straight or branched chain; —O—(C
1
-C
6
)-alkyl, in which alkyl is a strai

Affiliated with

Also associated with

Rating

Hydroperylene derivatives does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Hydroperylene derivatives, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Hydroperylene derivatives will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3215370