- Oxamic acid analogues as LDH-C4-specific competitive inhibitors
-
We performed kinetic studies to determine whether oxamate analogues are selective inhibitors of LDH-C4, owing to their potential usefulness in fertility control and treatment of some cancers. These substances were shown to be competitive inhibitors of LDH isozymes and are able to discriminate among subtle differences that differentiate the active sites of LDH-A4, LDH-B4 and LDH-C4. N-Ethyl oxamate was the most potent inhibitor showing the highest affinity for LDH-C4. However, N-propyl oxamate was the most selective inhibitor showing a high degree of selectivity towards LDH-C4. Non-polar four carbon atoms chains, linear or branched, dramatically diminished the affinity and selectivity towards LDH-C4. N-Propyl oxamate significantly reduced ATP levels, capacitation and mouse sperm motility, in line with results shown by others, suggesting that LDH-C4 plays an essential role in mouse fertility.
- Rodriguez-Paez, Lorena,Chena-Taboada, Miguel Angel,Cabrera-Hernandez, Arturo,Cordero-Martinez, Joaquin,Wong, Carlos
-
-
Read Online
- Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
-
A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
- Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
-
p. 6942 - 6990
(2017/09/07)
-
- 3. 4 - diphenyl - 4H - 1, 2, 4 - triazole derivative and its preparation method and application (by machine translation)
-
The invention discloses 3, 4 - diphenyl - 4H - 1, 2, 4 - triazole derivative and its preparation method and application. In particular, the invention relates to the formula (I) structure of 3, 4 - diphenyl - 4H - 1, 2, 4 - triazole derivatives, its stereoisomers or its pharmaceutically acceptable salt, formula (I) in the definition of each substituent is as defined in the specification. These structure of novel compound with heat shock protein HSP90 inhibitory activity, can be used for treating cancer, neurodegenerative diseases, inflammatory diseases, autoimmune diseases, ischemic brain injury and the like, it has broad application prospects. (by machine translation)
- -
-
Paragraph 0295; 0296; 0297; 0298
(2017/07/01)
-
- PYRAZINONE DERIVATIVES AS INSULIN SECRETION STIMULATORS, METHODS FOR OBTAINING THEM AND USE THEREOF FOR THE TREATMENT OF DIABETES
-
The present invention relates to pyrazinone derivatives of formula (I), wherein n, R1, R2, R3 and R4 are as defined in claim 1, as insulin secretion stimulators. The invention also relates to the preparation and use of these pyrazinone derivatives for the
- -
-
Page/Page column 28
(2009/10/22)
-
- ARYLPYRAZINONE DERIVATIVES INSULIN SECRETION STIMULATORS, METHODS FOR OBTAINING THEM AND USE THEREOF FOR THE TREATMENT OF DIABETES
-
The present invention relates to arylpyrazinone derivatives of formula (I), wherein R1, R2, R3 and A are as defined in claim 1, as insulin secretion stimulators. The invention also relates to the preparation and use of these pyrazinone derivatives for the
- -
-
Page/Page column 24-25
(2009/12/05)
-
- N-Boc ethyl oxamate: A new nitrogen nucleophile for use in Mitsunobu reactions
-
N-Boc ethyl oxamate can be directly coupled with primary and secondary alcohols under Mitsunobu conditions to afford various N-Boc mines after mild deprotection.
- Berree, Fabienne,Michelot, Gwendal,Le Corre, Maurice
-
p. 8275 - 8276
(2007/10/03)
-
- Hydrogen bond patterns in solid state carboxylic acids. Vibrational behaviour of the catamer pattern as exhibited by the N-alkyloxamic acids
-
The vibrational study presented in this publication shows that the N-alkyloxamic acids are hydrogen bonded through a catamer hydrogen bond pattern in the solid state. Two different hydrogen bond patterns are possible for these products, and these patterns can be very clearly distinguished by their vibrational behaviour. Deuteration and low temperature spectra make the assignment and characterisation more obvious.
- Wolfs, Ilse,Desseyn, Herman O.
-
p. 1521 - 1528
(2007/10/03)
-
- Synthesis of 1,3-Disubstituted Diazolidines
-
Symmetrical and unsymmetrical 1,3-diaminoethanes 1 are obtained by the reduction of N,N'-disubstituted oxamides 4 with lithium aluminum hydride.The oxamides 4 are readily produced by treatment of diethyl oxalate with primary amines.The 1,3-diaminoethanes 1 lead to 1,3-diazolidines 2 on treatment with formaldehyde.
- Lambert, Joseph B.,Huseland, Dave E.,Wang, Gen-tai
-
p. 657 - 658
(2007/10/02)
-