- SUBSTITUTED TRICYCLIC COMPOUNDS
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Disclosed are compounds of the general formula (I), its tautomeric form, its stereoisomer, its pharmaceutically acceptable salt, its polymorph, or solvate thereof, wherein, ring A, ring B, R1 to R4, and n are as defined herein, for use as SOS1 inhibitors in the treatment of proliferative, infectious and RASopathy diseases or disorders. Also disclosed are methods of synthesizing the compound of formula I, pharmaceutical compositions containing the compound of formula I, method of treatment of proliferative, infectious and RASopathy diseases or disorder, for example, a cancer, by administering the said compound and combinations of the compound of formula I with other active ingredients.
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Page/Page column 171-172
(2021/07/02)
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- Oxidation of aromatic and aliphatic aldehydes to carboxylic acids by Geotrichum candidum aldehyde dehydrogenase
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Oxidation reaction is one of the most important and indispensable organic reactions, so that green and sustainable catalysts for oxidation are necessary to be developed. Herein, biocatalytic oxidation of aldehydes was investigated, resulted in the synthesis of both aromatic and aliphatic carboxylic acids using a Geotrichum candidum aldehyde dehydrogenase (GcALDH). Moreover, selective oxidation of dialdehydes to aldehydic acids by GcALDH was also successful.
- Hoshino, Tomoyasu,Yamabe, Emi,Hawari, Muhammad Arisyi,Tamura, Mayumi,Kanamaru, Shuji,Yoshida, Keisuke,Koesoema, Afifa Ayu,Matsuda, Tomoko
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- Continuous synthesis method for substituted benzoic acid organic matter
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The invention provides a continuous synthesis method for a substituted benzoic acid organic matter. The continuous synthesis method comprises the following steps: in the presence of a catalyst and anorganic solvent, continuously putting an organic matter of a formula (I) shown in the specification, and oxygen into a continuous reaction device, carrying out a continuous oxidation reaction so as toobtain the substituted benzoic acid organic matter, and continuously discharging the substituted benzoic acid organic matter, wherein the substituted benzoic acid organic matter is of a structure ofa formula (II) shown in the specification. Oxygen is a green reagent and is cheap and easy to obtain, a great amount of wastes are not generated after reactions are completed, and the system is easy to treat. Due to continuous reaction operation, the risk that the solvent has flash evaporation explosion because of high-concentration oxygen in in-batch reactions can be reduced. Under same oxidationconditions, due to a continuous preparation process, escape of oxygen can be reduced, the utilization rate of oxygen can be greatly increased, operation can be also simplified, the security of reactions can be improved, and the yield of the substituted benzoic acid organic matter can be increased.
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Paragraph 0117-0119; 0138
(2019/10/01)
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- PROTECTIVE GROUPS AND METHODS FOR PROTECTING BENZOXABOROLES OR OXABOROLES
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The present invention relates in part protective groups that can be used to reversibly protect benzoxaboroles and/or oxaboroles and yield the corresponding protected complexes. The invention further relates to the use of these protective groups to protect benzoxaboroles and/or oxaboroles.
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Page/Page column 37
(2019/10/01)
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- Structural diversity, luminescence and photocatalytic properties of six coordination polymers based on designed bifunctional 2-(imidazol-1-yl)terephthalic acid
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Six coordination polymers (CPs), {[M(ITA)]·0.5H2O}n (M = Zn 1, M = Mn 2), {[Zn(ITA)(bib)0.5]·1.5H2O}n (3), {[Ni(ITA)(bib)0.5(H2O)3]·H2O}n (4), {[Zn(ITA)(bimb)0.5]·0.5H2O}n (5) and [Cd(ITA)(bimb)0.5(H2O)2]n (6), have been derived from the designed bifunctional 2-(imidazol-1-yl)terephthalic acid (H2ITA) with or without bis(imidazole) linkers (bib = 1,4-bis(imidazol-1-yl)benzene, bimb = 1,4-bis(imidazol-1-ylmethyl)benzene). X-Ray single-crystal diffraction analysis reveals that complexes 1 and 2 are isomorphic with the same 3D (4)-connected {4·63·82} net. Complex 3 features a 3D 2-fold interpenetrated (3,4)-connected fsc net with point symbol of {4·82·103}{4·82}. Complex 4 displays a 2D 3-connected {63)-hcb sheet, which can be further expanded into a 3D supramolecular network through hydrogen bonding interactions. Complex 5 exhibits an unprecedented 3D 2-fold interpenetrated (3,4)-connected dmc net with point symbol of {4·82}{4·85}. Complex 6 shows a 3D (3,4)-connected {4·82·103}{4·82}-fsc net. Structural comparison reveals that not only the coordination preferences of metal ions but also the auxiliary bis(imidazole) linkers play crucial roles in the control of the final structures. Besides, the photoluminescence properties as well as the photocatalytic activities for the degradation of methylene blue (MB) under UV-vis light of 1, 3, 5 and 6 have been investigated.
- Zhang, Xiutang,Fan, Liming,Fan, Weiliu,Li, Bin,Liu, Guangzeng,Liu, Xinzheng,Zhao, Xian
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p. 6914 - 6925
(2016/09/23)
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- Entropy effect of alkyl tails on phase behaviors of side-chain-jacketed polyacetylenes: Columnar phase and isotropic phase reentry
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We have investigated phase behaviors of a series of polyphenylacetylene derivatives, poly[di(n-alkyl) ethynylterephthalates] (Pn, n is the number of carbon atoms of n-alkyl group, from 2 to 14), which are largely influenced by the length of n-alkyl tails on 2,5-position of the phenyl group. With short alkyl groups (n ≤ 6), Pns form columnar liquid crystalline (Col) phases due to the "jacketing effect" of side-chains. As the alkyl tails become longer (n ≥ 8), an isotropic phase, which can be considered as a reentrant one (Ire), is identified between lamellar phase (Lam) at low temperatures and Col phase at high temperatures. This unusual phase behavior is determined by the motional state of the side-chains. Thanks to in-situ variable temperature solid-state NMR experiments, the motion of main- and side-chains in different phases were distinguished, providing strong evidence for the entropy effect of side-chains which drives Ire and then Col phase in Pns (n ≥ 8) upon heating.
- Liu, Xiaoqing,Wang, Jun,Yang, Shuang,Men, Yongfeng,Sun, Pingchuan,Chen, Er-Qiang
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p. 260 - 267
(2016/02/26)
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- Chalcone–benzoxaborole hybrids as novel anticancer agents
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In this study, we report the synthesis of a series of chalcone–benzoxaborole hybrid molecules and the evaluation of their anticancer activity. Their anticancer potency and toxicity were tested on three human cancer cell lines and two normal cell lines. The 4-fluoro compound 15 was found to be the most potent compound with an IC50value of 1.4 μM on SKOV3 cells. The 4-iodo compound 18 and 3-methyloxy-4-amino compound 47 showed good potency on SKOV3 cells while exhibiting low toxicity on normal cells. This work extended the application of benzoxaboroles to the field of anticancer research.
- Zhang, Jiong,Yang, Fei,Qiao, Zhitao,Zhu, Mingyan,Zhou, Huchen
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p. 5797 - 5801
(2016/11/28)
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- ANTIDIABETIC TRICYCLIC COMPOUNDS
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Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR 40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds may be useful in the treatment of Type 2 diabetes mellitus and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.
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Page/Page column 73
(2015/12/08)
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- BENZOXABOROLE FUNGICIDES
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Compounds of formula (I) are as defined in the claims, and their use in compositions and methods for the control and/or prevention of microbial infection, particularly fungal infection, in plants and to processes for the preparation of these compounds.
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Page/Page column 46; 47
(2015/07/15)
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- Small-molecule ligands of methyl-lysine binding proteins: Optimization of selectivity for L3MBTL3
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Lysine methylation is a key epigenetic mark, the dysregulation of which is linked to many diseases. Small-molecule antagonism of methyl-lysine (Kme) binding proteins that recognize such epigenetic marks can improve our understanding of these regulatory mechanisms and potentially validate Kme binding proteins as drug-discovery targets. We previously reported the discovery of 1 (UNC1215), the first potent and selective small-molecule chemical probe of a methyl-lysine reader protein, L3MBTL3, which antagonizes the mono- and dimethyl-lysine reading function of L3MBTL3. The design, synthesis, and structure-activity relationship studies that led to the discovery of 1 are described herein. These efforts established the requirements for potent L3MBTL3 binding and enabled the design of novel antagonists, such as compound 2 (UNC1679), that maintain in vitro and cellular potency with improved selectivity against other MBT-containing proteins. The antagonists described were also found to effectively interact with unlabeled endogenous L3MBTL3 in cells.
- James, Lindsey I.,Korboukh, Victoria K.,Krichevsky, Liubov,Baughman, Brandi M.,Herold, J. Martin,Norris, Jacqueline L.,Jin, Jian,Kireev, Dmitri B.,Janzen, William P.,Arrowsmith, Cheryl H.,Frye, Stephen V.
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supporting information
p. 7358 - 7371
(2013/10/21)
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- Chalcone-benzoxaborole hybrid molecules as potent antitrypanosomal agents
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We report the novel chalcone-benzoxaborole hybrids and their structure-activity relationship againstTrypanosoma brucei parasites. The 4-NH2 derivative 29 and 3-OMe derivative 43 were found to have excellent potency. The synergistic 4-NH2-3-OMe compound 49 showed an IC50 of 0.010 μ/mL and resulted in 100% survival and zero parasitemia in a murine infection model, which represents one of the most potent compounds discovered to date from the benzoxaborole class that inhibit T. brucei growth.
- Qiao, Zhitao,Wang, Qi,Zhang, Fenglong,Wang, Zhongli,Bowling, Tana,Nare, Bakela,Jacobs, Robert T.,Zhang, Jiong,Ding, Dazhong,Liu, Yangang,Zhou, Huchen
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supporting information; experimental part
p. 3553 - 3557
(2012/06/17)
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- Syntheses and crystal structures of three coordination polymers based on terphenyl-2,5,2,5-tetracarboxylic acid
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Solvothermal reactions of terphenyl-2,5,2,5-tetracarboxylic acid (H 4qptc) and MII (M=Co, Ni, Cu) in the presence of 2,2-bipyridine (2,2-bpy) afford three new coordination polymers, [M(qptc) 0.5(2,2-bpy)(H2O)]n (M=Co (1), Ni (2)) and [Cu(H2qptc)(2,2-bpy)]n (3). The structures have been determined by single-crystal X-ray diffraction analyses and further characterized by elemental analyses, IR, and TGA. Complexes 1 and 2 are isostructural and display a 2-D layer wherein qptc4 is a twisted H-shaped ligand connecting CoII centers. Furthermore, 3-D structures in 1 and 2 are formed via inter-chain interactions between neighboring 2,2-bpy ligands, with the centroid-centroid distances of 3.619-3.822. In 3, two deprotonated carboxyl groups of H2qptc2 are a Z-shaped ligand linking CuII centers to a 1-D zigzag polymeric chain. A 2-D layer structure is built with the help of inter-chain interactions between the 2,2-bpy and H2qptc2.
- Zhang, Xiutang,Fan, Liming,Sun, Zhong,Zhang, Wei,Li, Dacheng,Wei, Peihai,Li, Bin,Dou, Jianmin
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p. 3205 - 3215
(2012/11/13)
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- PROLYL HYDROXYLASE INHIBITORS
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The invention described herein relates to certain 2,4-dioxo-l,2,3,4-tetrahydro-7- quinazolinecarboxamide derivatives of formula (I) which are antagonists of HIF prolyl hydroxylases and are useful for treating diseases benefiting from the inhibition of this enzyme, anemia being one example.
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Page/Page column 23-24
(2010/07/10)
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- Convenient and versatile synthesis of formyl-substituted benzoxaboroles
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Despite of the medicinal significance of benzoxaboroles, with the newly discovered clinical compound AN2690 as an example, the synthetic method for rapid diversification of this novel scaffold is lacking. To this end, a versatile and scalable synthesis of formyl-substituted benzoxaboroles is described here. A key step is the mono-oxidation of the two hydroxyls in compound 4 by taking advantage of the stable oxaborole ring in non-coordinating solvents, which was devised based on the study of the intramolecular coordination and exchange properties.
- Ye, Long,Ding, Dazhong,Feng, Yiqing,Xie, Dongsheng,Wu, Puhua,Guo, Hui,Meng, Qingqing,Zhou, Huchen
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experimental part
p. 8738 - 8744
(2009/12/28)
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- PROCESS FOR THE SYNTHESIS OF HALOGENATED AROMATIC DIACIDS
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The production of high-purity halogenated aromatic diacids from halogenated dimethylbenzene by oxidation with an oxygen-containing gas is conducted using a four-component catalyst system and a two-stage temperature process.
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Page/Page column 16-17
(2008/12/07)
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- Naaladase inhibitors for treating retinal disorders and glaucoma
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The present invention relates to pharmaceutical compositions and methods for treating a retinal disorder or glaucoma using NAALADase inhibitors.
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- Naaladase inhibitors for treating amyotrophic lateral sclerosis
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The present invention relates to pharmaceutical compositions and methods for treating amyotrophic lateral sclerosis using NAALADase inhibitors.
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- Benzenedicarboxylic acid derivatives
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New benzenedicarboxylic acid derivative compounds; pharmaceutical compositions, diagnostic methods, and diagnstic kits that include those compounds; and methods of using those compounds for inhibiting NAALADase enzyme activity, detecting diseases where NAALADase levels are altered, effecting neuronal activity, effecting TGF-β activity, inhibiting angiogenesis, and treating glutamate abnormalities, neutopathy, pain, compulsive disorders, prostate diseases, cancers, and glaucoma.
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- Polymerizable biaryls, method for the production and use thereof
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A process for preparing polymerizable biaryl derivatives comprises reacting an aromatic comprising a 6-membered ring which bears ester or benzylic OH groups in the 1,4 position with a second aromatic in a palladium-catalyzed cross-coupling reaction to give a biaryl and converting the ester or benzylic OH groups into polymerizable groups in one or more steps. The biaryls obtained are suitable for preparing polymers which are used as electroluminescence materials.
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