10068-07-2Relevant articles and documents
4,5-Substituted 3-Isoxazolols with Insecticidal Activity Act as Competitive Antagonists of Housefly GABA Receptors
Liu, Genyan,Ozoe, Fumiyo,Furuta, Kenjiro,Ozoe, Yoshihisa
, p. 6304 - 6312 (2015)
The insect GABA receptor (GABAR), which is composed of five RDL subunits, represents an important target for insecticides. A series of 4,5-disubstituted 3-isoxazolols, including muscimol analogues, were synthesized and examined for their activities agains
Discovery of Potent, Selective, and Direct Acid Sphingomyelinase Inhibitors with Antidepressant Activity
Yang, Kan,Yu, Jinying,Nong, Keyi,Wang, Youzhi,Niu, Ao,Chen, Wenlu,Dong, Jibin,Wang, Jinxin
, p. 961 - 974 (2020)
Recent studies on sphingolipids suggest that acid sphingomyelinase (ASM), which plays a central role in the pathogenesis of major depression, is emerging to be a novel target for developing antidepressants. Herein we first described the design, synthesis,
NOVEL COMPOUNDS AND THEIR USES AS THYROID HORMONE RECEPTOR AGONISTS
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Page/Page column 30-31, (2020/09/08)
A compound of formula (I) or (Ia), or a tautomer or a pharmaceutically acceptable salt thereof is provided. Compounds of formula (II) to (V), or a tautomer or a pharmaceutically acceptable salt thereof are also provided. These compounds and the pharmaceutical compositions containing them are useful for the treatment of diseases such as obesity, hyperlipidemia, hypercholesterolemia and diabetes and other related disorders and diseases, and may be useful for other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other disorders and diseases related thereto． (I), (Ia)
Alkoxy isoxazole derivative as well as preparation method and application thereof (by machine translation)
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Paragraph 0106-0108, (2020/08/27)
The invention belongs to the field of pharmaceutical chemistry, and discloses an alkoxy isoxazole derivative represented by a formula (I) and a pharmaceutically acceptable salt thereof and a synthetic method and application thereof. The alkoxy isoxazole derivative has good affinity for sigma receptors, wherein a part of the compound has good membrane permeability, has a nerve regeneration promoting activity, and is expected to be developed into a medicine for treating central nervous system diseases, particularly neurodegenerative diseases. The sigma receptor has sigma - 1 and sigma - 2 two subtypes, wherein sigma - 1 is a target for treating central nervous system diseases, cocaine addiction and analgesia and the like, sigma - 2 is a therapeutic target for antitumor drugs. (by machine translation)
Discovery of: N -cyclobutylaminoethoxyisoxazole derivatives as novel sigma-1 receptor ligands with neurite outgrowth efficacy in cells
Sun, Hao,Wang, Yun-Jie,Shi, Wen-Wen,Yang, Fan,Tang, Jie,Pang, Tao,Yu, Li-Fang
, p. 7080 - 7088 (2018/02/23)
Herein we reported a series of 14 novel derivatives based on the N-cyclobutylaminoethoxyisoxazole scaffold. In vitro binding studies of these compounds demonstrated their low nanomolar to subnanomolar potencies as σ1 receptor ligands, with moderate to excellent selectivity over the σ2 receptor as represented by compounds 17-30. The majority of the derivatives scored high (>4.7) in the CNS MPO appraisal system, indicating their high likelihood in penetrating the blood-brain barrier. A number of these compounds exhibited significant neurite outgrowth efficacy in N1E-115 neuronal cells and displayed excellent selectivity for σ1 receptors over the selected endogenous neurotransmitter transporters, such as DAT, NET and SERT. Among the mini-series, compound 28 (Ki σ1 = 0.2 nM, Ki σ2 = 198 nM, CNS MPO score = 5.4) emerged as a promising selective σ1 receptor ligand that warrants its further evaluation as a potential therapeutic for neurodegenerative diseases.
Development of Novel Alkoxyisoxazoles as Sigma-1 Receptor Antagonists with Antinociceptive Efficacy
Sun, Hao,Shi, Min,Zhang, Wei,Zheng, Yue-Ming,Xu, Ya-Zhou,Shi, Jun-Jie,Liu, Ting,Gunosewoyo, Hendra,Pang, Tao,Gao, Zhao-Bing,Yang, Fan,Tang, Jie,Yu, Li-Fang
, p. 6329 - 6343 (2016/07/26)
A novel series of sigma (σ) receptor ligands based on an alkoxyisoxazole scaffold has been designed and synthesized. Preliminary receptor binding assays identified highly potent (Ki 1 nM) and selective σ1 ligands devoid of binding interactions with the monoamine transporters DAT, NET, and SERT. In particular, compound 53 was shown to possess significant antinociceptive activity in the mouse formalin-induced inflammation pain model when administered intraperitoneally at 40 and 80 mg/kg. Initial pharmacokinetics evaluation indicated an excellent brain exposure following oral dosing in mice, suggesting that further investigation into the use of alkoxyisoxazoles as σ1 ligands for antinociception is warranted. This study supports the notion that selective σ1 antagonism could be a useful strategy in the development of novel antipain therapy.
Process Research and Development of an Enantiomerically Enriched Allyic Amine, One of the Key Intermediates for the Manufacture of Synthetic Tetracyclines
Zhang, Wu-Yan,Hogan, Philip C.,Chen, Chi-Li,Niu, John,Wang, Zhimin,Lafrance, Danny,Gilicky, Olga,Dunwoody, Nicholas,Ronn, Magnus
, p. 1784 - 1795 (2015/12/01)
A robust, cost-effective, and high yielding manufacturing process for enantiomerically enriched (S)-allylic amine 3, a key intermediate for fully synthetic tetracyclines have been developed. Two novel and scalable asymmetric vinylations resulting in high-to-excellent stereoselectivity have been developed for the key step. The final product is purified by an efficient crystallization of a l-tartaric salt. The process described has been used to manufacture ～350 kg of the tartaric salt of 3 with 99.0% ee in 8 steps (35% overall yield) from cheap and readily available dimethyl maleate.
Identification of novel α4β2-nicotinic acetylcholine receptor (nAChR) agonists based on an isoxazole ether scaffold that demonstrate antidepressant-like activity
Yu, Li-Fang,Tückmantel, Werner,Eaton, J. Brek,Caldarone, Barbara,Fedolak, Allison,Hanania, Taleen,Brunner, Dani,Lukas, Ronald J.,Kozikowski, Alan P.
scheme or table, p. 812 - 823 (2012/03/26)
There is considerable evidence to support the hypothesis that the blockade of nAChR is responsible for the antidepressant action of nicotinic ligands. The nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine, has been shown to be an effective add-on in patients that do not respond to selective serotonin reuptake inhibitors. This suggests that nAChR ligands may address an unmet clinical need by providing relief from depressive symptoms in refractory patients. In this study, a new series of nAChR ligands based on an isoxazole-ether scaffold have been designed and synthesized for binding and functional assays. Preliminary structure-activity relationship (SAR) efforts identified a lead compound 43, which possesses potent antidepressant-like activity (1 mg/kg, IP; 5 mg/kg, PO) in the classical mouse forced swim test. Early stage absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) studies also suggested favorable drug-like properties, and broad screening toward other common neurotransmitter receptors indicated that compound 43 is highly selective for nAChRs over the other 45 neurotransmitter receptors and transporters tested.
ISOXAZOLE-ISOXAZOLES AND ISOXAZOLE-ISOTHIAZOLES
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Page/Page column 16, (2010/08/22)
The present invention is concerned with isoxazole-isoxazoles and isoxazole-isothiazoles of formula I, having affinity and selectivity for GABA A α5 receptor, their manufacture, pharmaceutical compositions containing them and their use as cognitive enhancers or for the therapeutic and/or prophylactic treatment of cognitive disorders like Alzheimer's disease.
Substituted 1,2,4-triazolo[3,4-a]phthalazine derivatives as GABA alpha 5 ligands
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, (2008/06/13)
Substituted 1,2,4-Triazolo[3,4-A]phthalazine derivatives are GABA Alpha 5 ligands and are represented by the formula
