- PYRAZOLYL-AMINO-SUBSTITUTED PYRAZINES AND THEIR USE FOR THE TREATMENT OF CANCER
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The present invention relates to compounds of Formula (I): and to their pharmaceutical compositions, and to their methods of use. These novel compounds provide a treatment for myeloproliferative disorders and cancer.
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Page/Page column 69
(2008/12/04)
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- Process for preparing 1,2,4-thiadiazole derivatives
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An improved process for the production of 5-amino-1,2,4-thiadiazol-3-yl-(2-(lower)-alkoxyimino)acetic acids starting from 5-substituted- or unsubstituted-3-amino-isoxazole compounds is disclosed herein. The title compounds are useful as acylating agents for the production of 7-acylaminocephalosporins.
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- Practical preparation of (Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methoxyiminoacetic acid: A side-chain of the fourth generation of cephem antibiotics
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A Z-isomer (4) of 2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)acetic acid, which is the common acyl moiety of clinically useful cephem antibiotics, has been prepared from the aminoisoxazoles through the skeletal rearrangement in several routes. Reaction of 3-amino-5-methoxyisoxazole (7) with alkoxycarbonyl isothiocyanates gave methyl 2-(5-alkoxycarbonylamino-1,2,4-thiadiazol-3-yl)acetates (8), which were converted into the target compound 4 through the reaction of the corresponding keto ester with O-methylhydroxylamime. Compound 4 was prepared similarly from 3-aminoisoxazole (10). Also, O-methylation of 2-hydroxyimino-2-(5-methoxycarbonylamino-1,2,4-thiazol-3-yl)acetate (15) with methyl iodide or dimethyl sulfate in the presence of barium oxide and barium hydroxide octahydrate was found to afford exclusively the desired Z-isomer (14a) of methyl 2-(5-methoxycarbonylamino-1,2,4-thiadiazol-3-yl)-2-(methoxyimino)aceta te, which was led to 4.
- Tatsuta,Miura,Gunji,Tamai,Yoshida,Inagaki,Kurita
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p. 1701 - 1707
(2007/10/02)
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- Synthesis and evaluation of antiinflammatory activities of a series of corticosteroid 17α-esters containing a functional group
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A series of 21-desoxy-21-chlorocorticosteroids that contain a functionalized ester group at 17α has been prepared and examined to separate their systemic activity from topical antiinflammatory activity. Introduction of the functionalized ester group at 17α was carried out by an acid-catalyzed formation of cyclic ortho esters with 17α,21-hydroxyl groups of corticosteroids and subsequent acid-catalyzed hydrolysis. As for the functional group, chloro, methoxy, acetoxy, cyano, cyclopropyl, or alkoxycarbonyl group was introduced at the terminal carbon atom of the 17α-alkanoate group. The topical antiinflammatory activity and systemic activity of these compounds were examined and found to be signficantly dependent on the functionalities in the 17α-esters. Among these derivatives, a series of 17α-(alkoxycarbonyl)alkanoates (17α-OCO(CH2)(n)COOR) showed an excellent separation of the systemic activity from topical activity. The effects of the number of methylene groups (n) and of the alkyl groups of the ester (R) on either topical or systemic activity of the corticosteroid derivatives were also investigated.
- Ueno,Maruyama,Miyake,Nakao,Nakao,Umezu,Nitta
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p. 2468 - 2473
(2007/10/02)
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