- 1,2,3-Triazole-containing uracil derivatives with excellent pharmacokinetics as a novel class of potent human deoxyuridine triphosphatase inhibitors
-
Deoxyuridine triphosphatase (dUTPase) has emerged as a potential target for drug development as a 5-fluorouracil-based combination chemotherapy. We describe the design and synthesis of a novel class of human dUTPase inhibitors, 1,2,3-triazole-containing u
- Miyakoshi, Hitoshi,Miyahara, Seiji,Yokogawa, Tatsushi,Endoh, Kanji,Muto, Toshiharu,Yano, Wakako,Wakasa, Takeshi,Ueno, Hiroyuki,Chong, Khoon Tee,Taguchi, Junko,Nomura, Makoto,Takao, Yayoi,Fujioka, Akio,Hashimoto, Akihiro,Itou, Kenjirou,Yamamura, Keisuke,Shuto, Satoshi,Nagasawa, Hideko,Fukuoka, Masayoshi
-
supporting information; experimental part
p. 6427 - 6437
(2012/09/22)
-
- COMPOUNDS AND METHOD FOR REDUCING URIC ACID
-
Uric acid in mammalian subjects is reduced and excretion of uric acid is increased by administering a compound of Formula (I) or a pharmaceutically acceptable salt thereof. In Formula (I) m is 0, 1, 2, 3 or 4; n is 0 or 1; m + n is not more than 4; t is 0 or 1; q is 0 or 1; and r is 0, 1 or 2. R6 is hydrogen, methyl or ethyl and R12 is hydrogen or methyl, or R6 is hydroxy and R12 is hydrogen, or R6 is O and R12 is absent, or R6 and R12 together are -CH2CH2-. R7 is hydrogen or alkyl having from 1 to 3 carbon atoms. One of R8 and R9 is alkyl having from 1 to 3 carbon atoms, and the other is hydrogen or alkyl having from 1 to 3 carbon atoms. R10 is hydrogen, halo, alkyl having from 1 to 3 carbon atoms or alkoxy having from 1 to 3 carbon atoms. X is C(O) and r is 0 and t is 0; or X is NH(R11) wherein R11 is hydrogen or alkyl having from 1 to 3 carbon atoms. A is phenyl, unsubstituted or substituted by 1 or 2 groups selected from halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy; or a 5 or 6 membered heteroaromatic ring having 1 or 2 ring heteroatoms selected from N, S and O and the heteroaromatic ring is covalently bound to the remainder of the compound of Formula (I) by a ring carbon; or cycloalkyl having from 3 to 6 ring carbon atoms wherein the cycloalkyl is unsubstituted or one or two ring carbons are independently monosubstituted by methyl or ethyl. The uric acid-lowering effects of the Compounds of Formula (I) are used to treat or prevent a variety of conditions including gout, hyperuricemia, elevated levels of uric acid that do not meet the levels customarily justifying a diagnosis of hyperuricemia, renal dysfunction, kidney stones, cardiovascular disease, risk for developing cardiovascular disease, tumor-lysis syndrome, and cognitive impairment.
- -
-
Page/Page column 81
(2010/01/07)
-
- Pyridoindolone derivatives substituted in the 3-position by a phenyl, their preparation and their application in therapeutics
-
The present invention relates to pyridoindolone derivatives substituted in the 3-position by a phenyl of general formula (I): to processes for preparing the same and to their use in therapeutics.
- -
-
Page/Page column 11
(2010/02/15)
-
- Regioselective synthesis of 1,8-dihydroxytetralins through a tandem reduction/intramolecular hydroxyalkylation of 4-(3-hydroxyphenyl)alkanoates
-
A series of 4-(3-hydroxyphenyl)butanoates 3 has been prepared and transformed into 1,8-dihydroxytetralins of general formula 2 by treatment with 2 equivalents of DIBALH followed by quenching with aqueous NH4Cl. A possible mechanism for this novel totally regioselective intramolecular hydroxyalkylation is suggested and the factors affecting the stability of 1,8-dihydroxytetralins 2 are also discussed.
- Guanti, Giuseppe,Banfi, Luca,Riva, Renata
-
p. 11945 - 11966
(2007/10/02)
-
- PYRAN DERIVATIVES AND THEIR USE AS INHIBITORS OF 5-LIPOXYGENASE
-
The invention concerns a cyclic ether derivative of the formula I, wherein Ar1 is optionally substituted phenyl, naphthyl or a 9-or 10-membered bicyclic heterocyclic moiety; A1 is a direct link to X1 or (l-3C)alkylene; X1 is oxy, thio, sulphinyl, sulphony
- -
-
-
- Tandem Reduction / Intramolecular Hydroxyalkylation of (3-Hydroxyphenyl)alkanoates: a New Regioselective Approach to 1,8-Dihydroxytetralins
-
4-(3-hydroxyphenyl)-butanoates 4, on treatment with DIBALH, followed by hydrolytic work-up, undergo a novel completely regioselective intramolecular hydroxyalkylation reaction to give 1,8-dihydroxytetralins.The yield of the reaction depends heavily on the structure of starting material, best results being achieved with 3,3-disubstituted butanoates.
- Guanti, Giuseppe,Banfi, Luca,Narisano, Enrica,Riva, Renata,Thea, Sergio
-
p. 3919 - 3922
(2007/10/02)
-