- Discovery of 3,5-dimethylisoxazole derivatives as novel, potent inhibitors for bromodomain and extraterminal domain (BET) family
-
Bromodomain and extra-terminal (BET) is a promising therapeutic target for various hematologic cancers. We used the BRD4 inhibitor compound 13 as a lead compound to develop a variety of compounds, and we introduced diverse groups into the position of the compound 13 orienting toward the ZA channel. A series of compounds (14–23, 38–41, 43, 47–49) bearing triazolopyridazine motif exhibited remarkable BRD4 protein inhibitory activities. Among them, compound 39 inhibited BRD4(BD1) protein with an IC50 of 0.003 μM was superior to lead compound 13. Meanwhile, compound 39 possess activity, IC50 = 2.1 μM, in antiproliferation activity against U266 cancer cells. On the other hand, compound 39 could arrest tumor cells into the G0/G1 phase and induce apoptosis, which was consistent with its results in inhibiting cell proliferation. Biological and biochemical data suggest that BRD4 protein might be a therapeutic target and that compound 39 is an excellent lead compound for further development.
- Fang, Lincheng,Hu, Zhaoxue,Yang, Yifei,Chen, Pan,Zhou, Jinpei,Zhang, Huibin
-
-
- Structural and Activity Relationships of 6-Sulfonyl-8-Nitrobenzothiazinones as Antitubercular Agents
-
The benzothiazinone (BTZ) scaffold compound PBTZ169 kills Mycobacterium tuberculosis by inhibiting the essential flavoenzyme DprE1, consequently blocking the synthesis of the cell wall component arabinans. While extraordinarily potent against M. tuberculosis with a minimum inhibitory concentration (MIC) less than 0.2 ng/mL, its low aqueous solubility and bioavailability issues need to be addressed. Here, we designed and synthesized a series of 6-methanesulfonyl substituted BTZ analogues; further exploration introduced five-member aromatic heterocycles as linkers to attach an aryl group as the side chain. Our work led to the discovery of a number of BTZ derived compounds with potent antitubercular activity. The optimized compounds 6 and 38 exhibited MIC 47 and 30 nM, respectively. Compared to PBTZ169, both compounds displayed increased aqueous solubility and higher stability in human liver microsomes. This study suggested that an alternative side-chain modification strategy could be implemented to improve the druglike properties of the BTZ-based compounds.
- Chiarelli, Laurent R.,Fan, Dongguang,Han, Quanquan,Lu, Yu,Qiao, Chunhua,Shi, Rui,Stelitano, Giovanni,Wang, Bin,Huszár, Stanislav,Miku?ová, Katarína,Savková, Karin
-
p. 14526 - 14539
(2021/10/26)
-
- Design, synthesis, fungicidal activities and structure–activity relationship studies of (?)-borneol derivatives containing 2-aryl-thiazole scaffold
-
A series of (-)-borneol derivatives containing 2-aryl-thiazole scaffold were designed, synthesized, and characterized by 1H NMR, 13C NMR, and HRMS. The fungicidal activities of these novel compounds against Fusarium oxysporum, Magnaporthe grisea, Botrytis cinerea, and Penicillium digitatum were evaluated. The results indicated that (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl(Z)-4-oxo-4-(((2-phenylthiazol-4-yl)methyl)amino)but-2-enoate (6a) displayed potential fungicidal activities with broad spectrum. Especially, 6a exhibited an IC50 value of 48.5 mg/L against P. digitatum, which has higher fungicidal activity than commercial products hymexazol and amicarthiazol. Moreover, (1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl-4-oxo-4-(((2-phenylthiazol-4-yl)methyl)amino)butanoate (5a) possesses an IC50 value of 24.3 mg/L against B. cinerea, comparable to hymexazol and far superior to amicarthiazol. Furthermore, the superficial structure–activity relationship was discussed, which might be helpful for discovering novel fungicides.
- Huang, Danling,Zheng, Shumin,Zhang, Tianyuan,Cheng, Yong-Xian
-
supporting information
(2021/06/07)
-
- Regioselectivity evaluation of the (Z)-5-(4-hydroxybenzylidene)-thiazolidine-2,4?dione alkylation in alkaline environment
-
Thiazolidine-2,4?dione represents a key heterocyclic core in medicinal chemistry because it has the ability to bind to a wide variety of protein targets and has been intensively studied for developing bioactive multitargeting agents. The N-alkylation of i
- Marc, Gabriel,Oniga, Ovidiu,Oniga, Smaranda,P?rn?u, Adrian,Stana, Anca,Vlase, Laurian
-
-
- Design, synthesis, and bioactivities of novel pyridazinone derivatives containing 2-phenylthiazole or oxazole skeletons
-
A series of novel pyridazinone derivatives were designed and synthesized by replacing 4-(tert-butyl)phenyl moiety of pyridaben with 2-phenylthiazole or oxazole fragments via activity substructure connecting approach. The structures of all target compounds were characterized through NMR, MS, and elemental analysis. Bioassay results exhibit that most compounds showed potent bioactivities against Aphis fabae, Tetranychus urticae, Erysiphe graminis, and/or Puccinia polysora. Among the newly synthesized compounds, 2-(tert-butyl)-4-chloro-5-(((2-phenylthiazol-4-yl)methyl)thio)pyridazin-3(2H)-one (12b) displays remarkable insecticidal activity against A fabae. Its LC50 value (2.73 mg/L) is better than that of pyridaben (5.46 mg/L), although inferior to that of imidacloprid (0.51 mg/L). In addition to its extraordinary insecticidal activity, compound 12b also exerts 96.9% fungicidal activities against P polysora at 500 mg/L in vivo, significantly superior to that of pyridaben (50.0%), while slightly lower than that of tebuconazole (100%). This article discusses the synthesis, bioassay results, and structure-activity relationship of this series of novel pyridazinone derivatives.
- Dang, Mingming,Liu, Minhua,Huang, Lu,Ou, Xiaoming,Long, Chuyun,Liu, Xingping,Ren, Yeguo,Zhang, Ping,Huang, Mingzhi,Liu, Aiping
-
p. 4088 - 4098
(2020/10/02)
-
- Discovery of first-in-class thiazole-based dual FFA1/PPARδ agonists as potential anti-diabetic agents
-
The free fatty acid receptor 1 (FFA1 or GPR40) and peroxisome proliferator-activated receptor δ (PPARδ) have attracted a lot of attention due to their role in promoting insulin secretion and sensibility, respectively, which are two major features of diabetes. Therefore, the dual FFA1/PPARδ agonists would increase insulin secretion and sensibility by FFA1 and PPARδ activation. In this study, we hybrid FFA1 agonist AM-4668 with PPARδ agonist GW501516, leading to the identification of orally bioavailable dual agonist 32, which revealed high selectivity over other PPARs. Moreover, compound 32 exhibited good pharmacokinetic profiles with high plasma concentration, sustained half-life and low clearance in vivo. During the hypoglycemic test, a dual agonist 32 enhanced the tolerance of ob/ob mice for glucose loading in a dose-dependent manner. Our results suggest that dual FFA1/PPARδ agonist could be a valuable therapy for type 2 diabetes.
- Li, Zheng,Chen, Yueming,Zhou, Zongtao,Deng, Liming,Xu, Yawen,Hu, Lijun,Liu, Bing,Zhang, Luyong
-
p. 352 - 365
(2019/01/04)
-
- Design, synthesis and fungicidal activity evaluation of novel pyrimidinamine derivatives containing phenyl-thiazole/oxazole moiety
-
Diflumetorim is a member of pyrimidinamine fungicides that possess excellent antifungal activities. Nevertheless, as reported that the activity of diflumetorim to corn rust (Puccinia sorghi) was not ideal (EC50 = 53.26 mg/L). Herein, a series of novel pyrimidinamine derivatives containing phenyl-thiazole/oxazole moiety were designed based on our previous study and the structural characteristics of diflumetorim, synthesized and bioassayed to discover novel fungicides with excellent antifungal activities. Among these compounds, T18 gave the optimal fungicidal activity, which respectively offers control effects with EC50 values of 0.93 mg/L against P. sorghi and 1.24 mg/L against E. graminis, significantly superior to commercial fungicides diflumetorim, tebuconazole, and flusilazole. Cell cytotoxicity results suggested that compound T18 has lower toxicities than diflumetorim. Furthermore, DFT calculation indicated that the phenyl-thiazole/oxazole moiety plays an unarguable role in the improvement of activity, which will contribute to designing and developing more potent compounds in the future.
- Yan, Zhongzhong,Liu, Aiping,Ou, Yingcan,Li, Jianming,Yi,Zhang, Ning,Liu, Minhua,Huang, Lu,Ren, Jianwei,Liu, Weidong,Hu, Aixi
-
p. 3218 - 3228
(2019/06/05)
-
- Organocatalyzed Domino Synthesis of New Thiazole-Based Decahydroacridine-1,8-diones and Dihydropyrido[2,3-d : 6,5-d′]- dipyrimidines in Water as Antimicrobial Agents
-
Organopromoter, 2-aminoethanesulfonic acid was used to catalyze the synthesis of a series of structurally intriguing new hybrids thiazolyl acridine-1,8(2H,5H)-diones and dihydropyrido[2,3-d : 6,5-d′]dipyrimidine-2,4,6,8(1H,3H,5H,7H)-tetraones for the firs
- Alkahtani, Hamad M.,Ansari, Siddique A.,Bhosle, Manisha R.,Bondle, Giribala M.,Kharote, Sayali A.,Sangshetti, Jaiprakash N.
-
-
- HETEROCYCLIC COMPOUND AND USE THEREOF
-
The present invention provides a heterocyclic compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I) : wherein each symbol is as described in the specification, or a salt thereof, is useful as an agent for the prophylaxis treatment of narcolepsy.
- -
-
Paragraph 0278
(2019/02/15)
-
- Tromethamine organocatalyzed efficient tandem-multicomponent synthesis of new thiazolyl-4-thiazolidinones in aqueous medium
-
The catalytic potential of tris(hydroxymethyl)aminomethane (Tromethamine) has been assessed for the one pot three component tandem reaction involving a thiazolylmethoxy phenyl/aromatic carboxaldehyde, substituted amines and thioglycolic acid to form new t
- Bhosle, Manisha R.,Kharote, Sayali A.,Bondle, Giribala M.,Mali, Jyotirling R.
-
p. 1286 - 1300
(2019/04/30)
-
- Design, synthesis, DFT study and antifungal activity of the derivatives of pyrazolecarboxamide containing thiazole or oxazole ring
-
Pyrazolecarboxamide fungicides are one of the most important classes of agricultural fungicides, which belong to succinodehydrogenase inhibitors (SDHIS). To discover new pyrazolecarboxamide analogues with broad spectrum and high activity, a class of new compounds of pyrazole carboxamide derivatives containing thiazole or oxazole ring were designed by scaffold hopping and bioisosterism, and 36 pyrazole carboxamide derivatives with antifungal activity were synthesized. Those compounds were evaluated against five phytopathogenic fungi, Gibberella zeae, Phytophythora capsici, Sclerotonia sclerotiorum, Erysiphe graminis and Puccinia sorghi. The results indicated that most of the compounds displayed good fungicidal activities, especially against E. graminis. Theoretical calculations were carried out at the B3LYP/6-31G (d, p) level and the full geometry optimization was carried out using the 6-31G (d, p) basis set, and the frontier orbital energy, atomic net charges, molecular docking were discussed, and the structure-activity relationships were also studied.
- Yan, Zhongzhong,Liu, Aiping,Huang, Mingzhi,Liu, Minhua,Pei, Hui,Huang, Lu,Yi, Haibo,Liu, Weidong,Hu, Aixi
-
p. 170 - 181
(2018/03/08)
-
- DYNAMIN-1-LIKE PROTEIN INHIBITORS
-
This application is directed to inhibitors of dynamin-l-like protein (Drpl) represented by the following structural formula (I): and methods for their use, such as to treat one or more DRPl-related diseases.
- -
-
-
- MALONONITRILE OXIME ETHER COMPOUND AND USE THEREOF
-
Disclosed is a malononitrile oxime ether compound having a novel structure as shown in the general formula I. Respective substituents in the general formula I as defined in the specification. The compound of the general formula I exhibits an excellent microbicidal activity, and can effectively prevent and treat plant diseases caused by bacteria and fungi. Also provided is a use of the compound of the general formula I as a microbicide in the agricultural and other fields.
- -
-
Paragraph 0095; 0096
(2019/01/04)
-
- Kinase inhibitor, and preparation and application of kinase inhibitor
-
The invention provides a compound shown as a formula (I), or a stereoisomer, a tautomer, nitrogen oxide, metabolite, a prodrug, pharmaceutically acceptable salt or solvate of the compound, and application of the compound to preparing drugs or drug compositions for treating Pim kinase-mediated diseases.
- -
-
Paragraph 0329-0333
(2018/09/11)
-
- Heterocycles 44. Synthesis, characterization and anticancer activity of new thiazole ortho-hydroxychalcones
-
A novel series of substituted thiazole ortho-hydroxychalcones was synthesized to be physico-chemically characterized and evaluated for the anticancer activity. The chalcones were synthesized with 28–68% yields, via Claisen–Schmidt condensation in an ethanolic solution. All the synthesized compounds were purified and characterized by MS, 1H NMR, 13C NMR, IR, and melting points. The cytotoxicity of thiazole ortho-hydroxychalcones 3a–3o as well as doxorubicin was determined in a panel of 9 cancer cell lines including sensitive and drug resistant phenotypes. Compounds 3a, 3b, 3c, 3j, as well as doxorubicin displayed cytotoxic effects in all the 9 tested cancer cell lines with IC50 values below 75 μM. The best samples showed IC50 values below 10 μM against 5/9 cancer cell lines for 3a, 3h, and 3o, against 7/9 cancer cell lines for 3c and 3f, and against 8/9 cancer cell lines for 3j. Hypersensitivity of all resistant cells towards 3b, 3g, 3j, 3m, and 3o was also obtained, suggesting that these compounds are appropriate molecules that could be used to combat drug resistance of cancer cells.
- Coman, Fana-Maria,Mbaveng, Armelle T.,Leonte, Denisa,Bencze, László Csaba,Vlase, Laurian,Imre, Silvia,Kuete, Victor,Efferth, Thomas,Zaharia, Valentin
-
p. 1396 - 1407
(2018/03/06)
-
- Synthesis and insecticidal activities of novel 1H-pyrazole-5-carboxylic acid derivatives
-
Fourteen 1H-pyrazole-5-carboxylic acid derivatives containing oxazole and thiazole rings were synthesized and characterized by 1H NMR, mass spectrometry and elemental analysis. Most target compounds were obtained in overall yields in the range of 30-50%. The insecticidal activities of these new compounds against Aphis fabae were evaluated. The bioassays' results indicate that some of these compounds exhibit good activities, especially compound 7h which shows 85.7% mortality against A. fabae at a concentration of 12.5 mg/L. This activity is comparable to that of the commercial insecticide imidacloprid.
- Huang, Danling,Liu, Aiping,Liu, Weidong,Liu, Xingping,Ren, Yeguo,Zheng, Xi,Pei, Hui,Xiang, Jun,Huang, Mingzhi,Wang, Xiaoguang
-
p. 455 - 460
(2017/12/18)
-
- SUBSTITUTED AND FUSED 6-MEMBERED PROTEASE ACTIVATED RECEPTOR 4 (PAR-4) ANTAGONISTS
-
Embodiments of the invention include compounds and compositions thereof to inhibit protease activated receptor-4. Also described are methods of preparation of compositions and methods for treating diseases related to thrombotic disorders by administration of the composition.
- -
-
Page/Page column 41
(2017/11/15)
-
- Pyrazole amide compound, and preparation method and application thereof
-
The invention discloses a pyrazole amide compound represented by the formula (I), and a preparation method and an application thereof, wherein R, R1, R2 and W have the definitions indicated in the specification. The compound represented by the formula (I) has bactericidal, insecticidal or acaricidal biological activities, and specially has quite high activity on pathogenic bacteria such as sphaerotheca fuliginea, botrytis cinerea, melampsora lini and the like.
- -
-
Paragraph 0101; 0102; 0108
(2017/06/02)
-
- Design, synthesis and biological evaluation of 1H-pyrazole-5-carboxamide derivatives as potential fungicidal and insecticidal agents
-
A series of novel 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety were designed and synthesized by a facile method, and their structures were characterized by 1H NMR, mass spectrometry and elemental analysis. Bioassay results showed that most of the title compounds showed potent fungicidal activities against Erysiphe graminis and insecticidal activity against Aphis fabae. Especially, compound 9b has EC50 values of 3.04 mg/L against Erysiphe graminis, of which the fungicidal activity is better than that of the commercial fungicide Thifluzamide and Azoxystrobinare; compound 9l has LC50 values of 3.81 mg/L against Aphis fabae, which was comparable with the commercial insecticide Tolfenpyrad. It is suggested that 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety could be considered as a precursor structure for further design of pesticides. Graphical Abstract: A series of novel 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety were designed and synthesized by a facile method, and their structures were characterized by 1H NMR, mass spectrometry and elemental analysis. Bioassay results showed that most of the title compounds showed potent fungicidal activities against Erysiphe graminis and insecticidal activity against Aphis fabae. Especially, compound 9b has EC50 values of 3.04 mg/L against Erysiphe graminis, of which the fungicidal activity is better than that of the commercial fungicide Thifluzamide and Azoxystrobinare; compound 9l has LC50 values of 3.81 mg/L against Aphis fabae, which was comparable with the commercial insecticide Tolfenpyrad. It is suggested that 1H-pyrazole-5-carboxamide compounds containing the phenyl thiazole moiety could be considered as a precursor structure for further design of pesticides.[Figure not available: see fulltext.]
- Huang, Danling,Huang, Mingzhi,Liu, Weidong,Liu, Aiping,Liu, Xingping,Chen, Xiaoyang,Pei, Hui,Sun, Jiong,Yin, Dulin,Wang, Xiaoguang
-
p. 2053 - 2061
(2017/09/30)
-
- Synthesis and Insecticidal Activity of Novel Thiazole Acrylonitrile Derivatives
-
A series of novel thiazole acrylonitrile derivatives was designed and synthesized utilizing NC-510 as a precursor. Their structures were characterized by NMR spectrometry, MS, and elemental analysis. The results of bioassay indicated that some of these ti
- Cao, Shengwen,Liu, Aiping,Liu, Weidong,Liu, Xingping,Ren, Yeguo,Pei, Hui,Huang, Lu,Zheng, Xi,Huang, Mingzhi,Wu, Daoxin
-
p. 3395 - 3402
(2017/11/21)
-
- Design, synthesis and Structure-activity relationship studies of new thiazole-based free fatty acid receptor 1 agonists for the treatment of type 2 diabetes
-
The free fatty acid receptor 1 (FFA1/GPR40) has attracted interest as a novel target for the treatment of type 2 diabetes. Several series of FFA1 agonists including TAK-875, the most advanced compound terminated in phase III studies due to concerns about liver toxicity, have been hampered by relatively high molecular weight and lipophilicity. Aiming to develop potent FFA1 agonists with low risk of liver toxicity by decreasing the lipophilicity, the middle phenyl of TAK-875 was replaced by 11 polar five-membered heteroaromatics. Subsequently, systematic exploration of SAR and application of molecular modeling, leads to the identification of compound 44, which was an excellent FFA1 agonist with robustly hypoglycemic effect both in normal and type 2 diabetic mice, low risks of hypoglycemia and liver toxicity even at the twice molar dose of TAK-875. Meanwhile, two important findings were noted. First, the methyl group in our thiazole series occupied a small hydrophobic subpocket which had no interactions with TAK-875. Furthermore, the agonistic activity revealed a good correlation with the dihedral angle between thiazole core and the terminal benzene ring. These results promote the understanding of ligand-binding pocket and might help to design more promising FFA1 agonists.
- Li, Zheng,Qiu, Qianqian,Xu, Xue,Wang, Xuekun,Jiao, Lei,Su, Xin,Pan, Miaobo,Huang, Wenlong,Qian, Hai
-
p. 246 - 257
(2016/03/08)
-
- Hit-to-Lead Optimization of a Novel Class of Potent, Broad-Spectrum Trypanosomacides
-
The parasitic trypanosomes Trypanosoma brucei and T. cruzi are responsible for significant human suffering in the form of human African trypanosomiasis (HAT) and Chagas disease. Drugs currently available to treat these neglected diseases leave much to be
- Russell, Stephanie,Rahmani, Rapha?l,Jones, Amy J.,Newson, Harriet L.,Neilde, Kevin,Cotillo, Ignacio,Rahmani Khajouei, Marzieh,Ferrins, Lori,Qureishi, Sana,Nguyen, Nghi,Martinez-Martinez, Maria S.,Weaver, Donald F.,Kaiser, Marcel,Riley, Jennifer,Thomas, John,De Rycker, Manu,Read, Kevin D.,Flematti, Gavin R.,Ryan, Eileen,Tanghe, Scott,Rodriguez, Ana,Charman, Susan A.,Kessler, Albane,Avery, Vicky M.,Baell, Jonathan B.,Piggott, Matthew J.
-
p. 9686 - 9720
(2016/11/19)
-
- Pyrazolyl thiazolyl acrylonitrile compounds and use thereof
-
The present invention discloses a novel structure pyrazolyl thiazolyl acrylonitrile compound or a stereoisomer thereof, wherein the structure of the compound is represented by a general formula I, R1 is selected from C1-C6 alkyl, halogenated C1-C6 alkyl,
- -
-
Paragraph 0075; 0076; 0077
(2017/01/17)
-
- Thiazolyl acrylonitrile compound and use thereof
-
The invention discloses a thiazolyl acrylonitrile compound with novel structure or stereoisomers thereof. The compound has a general formula as shown in a general formula I. R is selected from C1-C6 alkyl, halogenated C1-C6 alkyl, C3-C8 cycloalkyl and C1-
- -
-
Paragraph 0066-0068
(2016/10/08)
-
- Phenyl thiazolyl acrylonitrile compound and use thereof
-
The invention discloses a phenyl thiazolyl acrylonitrile compound with novel structure or stereoisomers thereof. The compound has a structure as shown in a formula I. R1 is selected from C1-C6 alkyl, halogenated C1-C6 alkyl, C3-C8 cycloalkyl, C1-C6 alkylo
- -
-
Paragraph 0092-0094
(2016/10/08)
-
- 2- [...] azoly acrylonitrile compound and use thereof
-
The invention discloses a 2-chloro thiazolyl acrylonitrile compound or a stereisomer thereof with a novel structure. The structure of the compound is shown as the general formula I in the specification, wherein R is one of alkyl of C1-C6, halogenated alkyl of C1-C6, cycloalkyl of C3-C8 and alkoxy of C1-C6; Q is selected from the group shown as the specification; R1 is one of H, halogen, methyl and trifluoromethyl; R2 is one of H and halogen. The compound in the general formula I has excellent insect and mite killing activity, and can be used for preventing and controlling insects and mites.
- -
-
Paragraph 0100-0103
(2016/10/08)
-
- Stereoselective Synthesis of β-(5-Arylthiazolyl) α-Amino Acids and Use in Neurotensin Analogues
-
A series of new unnatural amino acids bearing a β-arylthiazole side chain was synthesized by exploiting a diastereoselective alkylation starting from glycine tert-butyl ester Schiff base with hydroxypinanone as the chiral inducer. This strategy afforded β-arylthiazole alanines in good chemical yields and with 98 % ee. Due to their aromatic properties, these newly generated amino acids were used to prepare neurotensin (NT)[8-13] analogues by serving as replacements for the native Tyr11 residue. Incorporation of the (L)-(+)-(β-phenylthiazol-4-yl)alanine residue at NT[8-13] position 11 improved plasma stability and selectivity towards NTS1, while also preserving native receptor binding affinity and biological activity. New β-arylthiazole alanines were synthesized in good chemical yields and with 98 % ee using a diastereoselective alkylation; these alanine derivatives were then used as Tyr11 replacements in the construction of neurotensin (NT)[8-13] analogues. The new NT analogues showed improved plasma stability and selectivity towards NTS1 thus preserving the hypotensive properties of the native peptide.
- Hap?u, Denisa,Rémond, Emmanuelle,Fanelli, Roberto,Vivancos, Mélanie,René, Adeline,C?té, Jér?me,Besserer-Offroy, élie,Longpré, Jean-Michel,Martinez, Jean,Zaharia, Valentin,Sarret, Philippe,Cavelier, Florine
-
p. 1017 - 1024
(2016/03/01)
-
- Acrylonitrile compound, and preparation method and application thereof
-
The invention discloses an acrylonitrile compound shown as the formula (I), and a preparation method and application thereof. Ar , Ar, R, W and Y in the formula (I) have definitions given in the description. The compound in the formula (I) has insec
- -
-
Paragraph 0109; 0111
(2017/10/24)
-
- HETEROCYCLIC COMPOUNDS AND USE OF SAME
-
Novel heterocyclic compounds are provided which display useful efficacy in the treatment of diseases caused by trypanosomatids. Particularly, the compounds of the invention are useful in the treatment of HAT and/or Chagas disease and/or Animal African trypanosomiasis (AAT).
- -
-
Paragraph 0025; 00208
(2016/01/08)
-
- AGONISTS OF THE APELIN RECEPTOR AND METHODS OF USE THEREOF
-
Provided herein are small molecule agonists of the apelin receptor for the treatment of disease. The compounds disclosed herein are useful for the treatment of a range of cardiovascular, renal and metabolic conditions.
- -
-
Paragraph 0268; 0269; 0270
(2015/12/31)
-
- Agonists for the adenosine A1 receptor with tunable residence time. a case for nonribose 4-amino-6-aryl-5-cyano-2-thiopyrimidines
-
We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A 1 receptor (hA1AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.
- Louvel, Julien,Guo, Dong,Agliardi, Marta,Mocking, Tamara A. M.,Kars, Roland,Pham, Tan Phát,Xia, Lizi,De Vries, Henk,Brussee, Johannes,Heitman, Laura H.,Ijzerman, Adriaan P.
-
p. 3213 - 3222
(2014/05/20)
-
- The effect of some 4,2 and 5,2 bisthiazole derivatives on nitro-oxidative stress and phagocytosis in acute experimental inflammation
-
Nineteen bisthiazoles were tested in order to assess their anti-inflammatory and antioxidant properties. First, we evaluated the in vitro direct antioxidant capacity of the bisthiazoles using the DPPH radical scavenging method. Then, the anti-inflammatory
- Araniciu, Catalin,Parvu, Alina Elena,Palage, Mariana Doina,Oniga, Smaranda Dafina,Benedec, Daniela,Oniga, Ilioara,Oniga, Ovidiu
-
p. 9240 - 9256
(2014/08/05)
-
- Synthesis and anticonvulsant activity of some non-classical dihydropyridine like structures
-
A series of dihydropyridine analogous was synthesized and evaluated for anticonvulsant activity using PTZ animal model. The main strategies are introducing a non-classical dihydropyridine like structure as anti-seizure agent. Some compounds showed signifi
- Sharifzadeh, Mohammad,Khademi, Hamid Reza,Almasirad, Ali,Rezayan, Zahra,Ghayahbashi, Mohsen Rezayan,Amini, Mohsen
-
p. 900 - 905
(2013/12/04)
-
- Heterocycles 32. Efficient kinetic resolution of 1-(2-arylthiazol-4-yl) ethanols and their acetates using lipase B from Candida antarctica
-
In this paper we describe the chemoenzymatic synthesis of new enantiomerically enriched (R)- and (S)-1-(2-arylthiazol-4-yl)ethanols and their acetates by enzymatic enantioselective acetylation of the racemic alcohols rac-2a-d and by methanolysis of the corresponding racemic esters rac-3a-d mediated by lipase B from Candida antarctica (CaL-B) in non-aqueous media. In terms of stereoselectivity and activity, both procedures, acylation and alcoholysis, gave similar good results (50% conversion, E 〉 200). The absolute configuration of the kinetic resolution products was determined by a detailed 1H NMR study of the Mosher's derivatives of (S)-2b.
- Hapau, Denisa,Brem, Juergen,Moisa, Madalina,Tosa, Monica-Ioana,Irimie, Florin Dan,Zaharia, Valentin
-
-
- ALKALOID AMINOESTER DERIVATIVES AND MEDICINAL COMPOSITION THEREOF
-
The present invention relates to alkaloid aminoester compounds which act as muscarinic receptor antagonists, processes for the preparation of such a compound, compositions which contain such a compound, and therapeutic uses of such a compound.
- -
-
-
- ALKALOID AMINOESTER DERIVATIVES AND MEDICINAL COMPOSITION THEREOF
-
The present invention relates to alkaloid aminoester derivatives acting as muscarinic receptor antagonists, processes for their preparation, compositions comprising them and therapeutic uses thereof.
- -
-
Page/Page column 65-66
(2012/01/13)
-
- 1-[(2-arylthiazol-4-yl)methyl]azoles as a new class of anticonvulsants: Design, synthesis, in vivo screening, and in silico drug-like properties
-
A series of novel thiazole incorporated (arylalkyl)azoles were synthesized and screened for their anticonvulsant properties using maximal electroshock and pentylenetetrazole models in mice. Among target compounds, 1-[(2-(4-chlorophenyl)thiazol-4-yl)methyl
- Ahangar, Nematollah,Ayati, Adile,Alipour, Eskandar,Pashapour, Arsalan,Foroumadi, Alireza,Emami, Saeed
-
experimental part
p. 844 - 852
(2012/07/14)
-
- Synthesis and in-vitro cytotoxicity of poly-functionalized 4-(2-arylthiazol-4-yl)-4H-chromenes
-
A new series of 4-aryl-4H-chromenes bearing a 2-arylthiazol-4-yl moiety at the 4-position were prepared as potential cytotoxic agents. The in-vitro cytotoxic activity of the synthesized 4-aryl-4H-chromenes was investigated in comparison with etoposide, a well-known anticancer drug, using MTT colorimetric assay. Among them, the 2-(2-chlorophenyl)thiazol-4-yl analog 4b showed the most potent activity against nasopharyngeal epidermoid carcinoma KB, medulloblastoma DAOY, and astrocytoma 1321N1, and compound 4d bearing a 2-(4-chlorophenyl) thiazol-4-yl moiety at the 4-position of the chromene ring exhibited the best inhibitory activity against breast cancer cells MCF-7, lung cancer cells A549, and colon adenocarcinoma cells SW480 with IC50 values less than 5 μM. The ability of compound 4b to induce apoptosis was confirmed in a nuclear morphological assay by DAPI staining in the KB and MCF-7 cells.
- Mahmoodi, Majid,Aliabadi, Alireza,Emami, Saeed,Safavi, Maliheh,Rajabalian, Saeed,Mohagheghi, Mohammad-Ali,Khoshzaban, Ahad,Samzadeh-Kermani, Alireza,Lamei, Navid,Shafiee, Abbas,Foroumadi, Alireza
-
p. 411 - 416
(2011/08/05)
-
- Synthesis and structure-activity relationships of 2-aryl-4-oxazolylmethoxy benzylglycines and 2-aryl-4-thiazolylmethoxy benzylglycines as novel, potent PPARα selective activators- PPARα and PPARγ selectivity modulation
-
The synthesis and follow-up SAR studies of our development candidate 1 by incorporating 2-aryl-4-oxazolylmethoxy and 2-aryl-4-thiazolylmethoxy moieties into the oxybenzylglycine framework of the PPARα/γ dual agonist muraglitazar is described. SAR studies indicate that different substituents on the aryloxazole/thiazole moieties as well as the choice of carbamate substituent on the glycine moiety can significantly modulate the selectivity of PPARα versus PPARγ. Potent, highly selective PPARα activators 2a and 2l, as well as PPARα activators with significant PPARγ activity, such as 2s, were identified. The in vivo pharmacology of these compounds in preclinical animal models as well as their ADME profiles are discussed.
- Ye, Xiang-Yang,Chen, Stephanie,Zhang, Hao,Locke, Kenneth T.,O'Malley, Kevin,Zhang, Litao,Srivastava, Raijit,Miao, Bowman,Meyers, Daniel,Monshizadegan, Hossain,Search, Debra,Grimm, Denise,Zhang, Rongan,Lippy, Jonathan,Twamley, Celeste,Muckelbauer, Jodi K.,Chang, Chiehying,An, Yongmi,Hosagrahara, Vinayak,Zhang, Lisa,Yang,Mukherjee, Ranjan,Cheng, Peter T.W.,Tino, Joseph A.
-
supporting information; experimental part
p. 2933 - 2937
(2010/08/19)
-
- ION CHANNEL MODULATORS
-
The present teachings provide compounds of Formula (I): and pharmaceutically acceptable salts, hydrates, and esters thereof, wherein Ar, R1, R2, R3, p, and X are defined herein. The present teachings also provide processes for producing said compounds and their pharmaceutically acceptable salts, hydrates and esters, and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds including their pharmaceutically acceptable salts, hydrates and esters. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.
- -
-
Page/Page column 124
(2008/12/06)
-
- ION CHANNEL MODULATORS
-
The present teachings provide compounds of Formula (I) and pharmaceutically acceptable salts, hydrates, and esters thereof, wherein Ar, R1, R1', R2, R3, R4 R4', and p are defined herein. The present teachings also provide processes for producing said compounds and their pharmaceutically acceptable salts, hydrates and esters, and methods of treating a pathological condition or disorder, or alleviating a symptom thereof, using said compounds including their pharmaceutically acceptable salts, hydrates and esters. The compounds can be useful in modulating ion channel activity including treating a variety of conditions associated with the abnormal modulation of one or more voltage-gated calcium channels.
- -
-
Page/Page column 82
(2008/12/06)
-
- Design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins
-
Flavivirus envelope proteins (E proteins) have been shown to play a pivotal role in virus assembly, morphogenesis, and infection of host cells. Inhibition of flavivirus infection of a host cell by means of a small molecule envelope protein antagonist is an attractive strategy for the development of antiviral agents. Virtual screening of the NCI chemical database using the dengue virus envelope protein structure revealed several hypothetical hit compounds. Bioassay results identified a class of thiazole compounds with antiviral potency in cell-based assays. Modification of these lead compounds led to a series of analogues with improved antiviral activity and decreased cytotoxicity. The most active compounds 11 and 36 were effective in the low micromolar concentration range in a cellular assay system.
- Li, Ze,Khaliq, Mansoora,Zhou, Zhigang,Post, Carol Beth,Kuhn, Richard J.,Cushman, Mark
-
scheme or table
p. 4660 - 4671
(2009/07/11)
-
- NOVEL 2-ARYLTHIAZOLE COMPOUNDS AS PPARALPHA AND PPARGAMA AGONISTS
-
The present invention relates to compounds of formula (I) wherein Rl to R10, X, Y and n are as defined in the description and claims, and pharmaceutically acceptable salts and esters thereof. The compounds are useful for the treatment of diseases such as diabetes.
- -
-
-
- PROCESS FOR PRODUCTION OF PYRAZOLE COMPOUNDS
-
As a method capable of conveniently producing a pyrazole compound in a high yield, which is useful as a synthetic intermediate for a pharmaceutical agent such as a therapeutic agent for diabetes and the like, a production method of a compound represented
- -
-
-
- Phenyloxazoles and phenylthiazoles as benzamide bioisosteres: Synthesis and dopamine receptor binding profiles
-
Conformationally restricted benzamide bioisosteres were investigated when the aminomethylpyrrolidine derivative 4o proved D3 as well as D4 binding properties which were comparable to those of the atypical neuroleptics sulpiride and clozapine, respectively. (C) 2000 Elsevier Science Ltd.
- Einsiedel, Juergen,Thomas, Christoph,Huebner, Harald,Gmeiner, Peter
-
p. 2041 - 2044
(2007/10/03)
-
- Etylene derivatives and pesticides containing said derivatives
-
Ethylene derivatives of formula (I): where Q is an unsubstituted or substituted phenyl or heterocyclic group, especially a 4-thiazolyl, 1- or 3-pyrazolyl, 1,3-oxazol-4-yl, phenyl or pyridyl group; E is a substituent such as a cyano group; A is a substituent such as a 4-pyrazolyl or thiazolyl group; and B is a substituent such as an alkylcarbonyl group. Agricultural chemicals and agents for preventing the attachment of aquatic organisms containing one or more such ethylene derivatives.
- -
-
-
- Azole phenoxy hydroxyureas as selective and orally active inhibitors of 5- lipoxygenase
-
Azole phenoxy hydroxyureas are a new class of 5-lipoxygenase (5-LO) inhibitors. Structure-activity relationship studies have demonstrated that electronegative substituents on the 2-phenyl portion of the oxazole tail increased the ex vivo potency of these
- Malamas,Carlson,Grimes,Howell,Glaser,Gunawan,Nelson,Kanzelberger,Shah,Hartman
-
p. 237 - 245
(2007/10/03)
-
- Certain 3,3'-[[[(2-phenyl-4-thiazolyl)methoxy]phenyl]methylene]dithiobis-propanoic acid derivatives
-
There are disclosed compounds of the formula STR1 wherein X is STR2 Y is STR3 Z is --(CH2)n O--, --(CH2)n S--, STR4 R1 is STR5 n is 0-5; R2 is hydrogen, loweralkyl, loweralkoxy, lower alkox
- -
-
-