Tricyclo compounds, a process for their production and a pharmaceutical composition containing the same
AssigneeFujisawa Pharmaceutical Co., Ltd.
InventorsMasakuni Okuhara, Hirokazu Tanaka, Toshio Goto, Tohru Kino, Hiroshi Hatanaka
Life of this patent
Estimating the term…
Abstract
This invention relates to tricyclo compounds useful for treatment and prevention of resistance by transplanation, graft-versus-host diseases by medulla ossium transplanation, autoimmune diseases, infectious diseases, and the like, which can be represented by the formula: 1 to a process for their production, to a pharmaceutical composition containing the same and to a use thereof.
Claims19
A compound of the formula:
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- wherein R1 is hydroxy or protected hydroxy, R2 is hydrogen, hydroxy or protected hydroxy, R is methyl, ethyl, propyl or allyl, n is an integer of 1 or 2, and the symbol of a line and dotted line is a single bond or a double bond, and salt thereof.
A compound of claim 3, wherein R1 hydroxy, 1-(lower alkythio) (lower)alkoxy, trisubstituted silyloxy or acyloxy.
A compound of claim 4, wherein R1 is hydroxy, lower alkylthiomethoxy, tri(lower)alkylsilyloxy, lower alkyl-diarylsilyloxy, lower alkanoyloxy which may have carboxy, cyclo(lower)alkoxy(lower)alkanoyloxy which may have two lower alkyl groups on the cycloalkyl moiety, camphorsulfonyloxy, carboxy(lower)alkylcarbamoyloxy, tri(lower)alkylsilyl(lower)alkoxycarbonyl(lower)-alkylcarbamoyloxy, aroyloxy which may have one or two nitro, arenesulfonyloxy which may have halogen or ar(lower)alkanoyloxy which may have lower alkoxy and trihalo(lower)alkyl, and R2 is hydroxy or lower alkanoyloxy.
A process for production of the compound of the formula:
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- wherein R1 is hydroxy or protected hydroxy, R2 is hydrogen, hydroxy or protected hydroxy, R3 is methyl, ethyl, propyl or allyl, n is an integer of 1 or 2, and the symbol of a line and dotted line is a single bond or a double bond, and salt thereof, which comprises
- (a) culturing a FR-900506, FR-900520 and/or FR-900525 substance(s)-producing strain belonging to the genus Streptomyces in a nutrient medium and recovering the FR-900506, FR-900520 and/or FR-900525 substance(s) to R3 the FR-900506, FR-900520 and/or FR-900525 substance(s);
- (b) culturing a FR-900520 and/or FR-900523 substance(s)-producing strain belonging to the genus Streptomyces in a nutrient medium and recovering the FR-900520 and/or FR-900523 substance(s) to give the FR-900520 and/or FR-900523 substance(s);
- (c) introducing a hydroxy-protective group into a compound of the formula:
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- wherein R2, R3 n and the symbol of a line and dotted line are each as defined above, to give a compound of the formula:
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- a
- wherein R2, R3, n and the symbol of a line and dotted line are each as defiend above, and R1 is protected hydroxy, or a salt thereof;
- (d) introducing a hydroxy-protective group into a compound of the formula:
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- wherein R1, R3, n and the symbol of a line and the dotted line are each as defined above, or a salt thereof, to give a compound of the formula:
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- wherein R1, R3, n and the symbol of a line and dotted line are each as defined above, and Ra2 is protected hydroxy, or a salt thereof;
- (3) reacting a compound of the formula:
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- wherein R1, R2 and n are each as defined above, and Rb2 is a leaving group, or a salt thereof with a base, to give a compound of the formula:
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- wherein R1, R3 and n are each as defined above, or a salt thereof;
- (f) oxidizing a compound of the formula:
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- wherein R1, R3 and n are each as defined above, or a salt thereof, to give a compound of the formula:
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- wherein R1, R3 and n are each as defiend above, or a salt thereof;
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- (g) reducing a compound of the formula:
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- wherein R1, R2, n and the symbol of a line and dotted line are each as defined above, or a salt thereof, to give a compound of the formula:
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- wherein R1, R2, n and the symbol of a line and dotted line are each as defined above, or a salt thereof, and (h) removing a carboxy-protective group from a compound of the formula:
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- wherein R2, R3, n and the symbol of a line and dotted line are each as defined above, and Rb1 is protected carboxy(lower)alkylcarbamoyloxy, or a salt thereof to give a compound of the formula:
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- wherein R2, R3, n and the symbol of a line and dotted line are each as defined above, and Rc1 is carboxy(lower)alkylcarbamoyloxy, or a salt thereof.
A biologically pure culture of the microorganism Streptomyces tsukubaensis No. 9993.
A biologically pure culture of the microorganisms Streptomyces hygrosconicus subsp. yakushimaensis No. 7238.
Dependencies are inferred from the claim text.