- Methylene violet derivative fluorescent probe as well as synthesis method and application thereof
-
The invention discloses a methylene violet derivative fluorescent probe as well as a synthesis method and application thereof. The fluorescent probe is connected with an NBD group through piperazine on the basis of a cationic main structure of methylene violet. The preparation method comprises the following steps: directly reacting methylene violet 3RAX with piperazine, or firstly reacting with X-R5-X and then reacting with piperazine, and finally introducing an NBD group to a piperazine group to obtain the target fluorescent probe; or reacting 4-fluoronitrobenzene, piperazine and aniline to obtain a cationic main structure of methylene violet, and finally introducing an NBD group to a piperazine group to obtain the target fluorescent probe. The fluorescent probe is good in water solubility, can be used for sulfur ion detection, is high in detection sensitivity and low in detection limit, and can also be used as a tumor photodynamic therapy probe to quickly release singlet oxygen for tumor photodynamic therapy; synthesis is simple, conditions are mild, and cost is low.
- -
-
Paragraph 0052-0056
(2021/03/13)
-
- Synthesis and structure-activity relationships of new 2-phenoxybenzamides with antiplasmodial activity
-
The 2-phenoxybenzamide 1 from the Medicines for Malaria Venture Malaria Box Project has shown promising multi-stage activity against different strains of P. falciparum. It was successfully synthesized via a retrosynthetic approach. Subsequently, twenty-one new derivatives were prepared and tested for their in vitro activity against blood stages of the NF54 strain of P. falciparum. Several insights into structure-activity relationships were revealed. The antiplasmodial activity and cytotoxicity of compounds strongly depended on the substitution pattern of the anilino partial structure as well as on the size of substituents. The diaryl ether partial structure had further impacts on the activity. Additionally, several physicochemical and pharmacokinetic parameters were calculated (log P, log D7.4 and ligand efficiency) or determined experimentally (passive permeability and CYP3A4 inhibition). The tert-butyl-4-{4-[2-(4-fluorophenoxy)-3-(trifluoromethyl)benzamido]phenyl}piperazine-1-carboxylate possesses high antiplasmodial activity against P. falciparum NF54 (PfNF54 IC50 = 0.2690 μM) and very low cytotoxicity (L-6 cells IC50 = 124.0 μM) resulting in an excellent selectivity index of 460. Compared to the lead structure 1 the antiplasmodial activity was improved as well as the physicochemical and some pharmacokinetic parameters.
- Dolensky, Johanna,Hermann, Theresa,Hochegger, Patrick,Kaiser, Marcel,M?ser, Pascal,Pferschy-Wenzig, Eva-Maria,Saf, Robert,Seebacher, Werner,Weis, Robert
-
-
- Toll-like receptor-7 small molecule inhibitor and preparation method thereof
-
The invention belongs to the field of chemical small molecules, and particularly relates to a Toll-like receptor-7 small molecule inhibitor. The invention provides the Toll-like receptor-7 small molecule inhibitor, which takes a co-inhibitor of TLR7 and TLR8 obtained by screening as a research object, realizes selective regulation and control of TLR7 and TLR8 through the research on the structureoptimization and structure-activity relationship (SAR) of a parent compound, and further develops a high-efficiency, non-toxic and specific small molecule inhibitor with certain selectivity on TLR 7.The TLR7 small molecule inhibitor has a certain effect and potential medicinal value in autoimmune diseases (systemic lupus erythematosus).
- -
-
Paragraph 0147; 0150-0151
(2021/02/24)
-
- Five-membered heteroaromatic ring derivative as well as preparation method and application thereof
-
The invention discloses a five-membered heteroaromatic ring derivative and a preparation method and application thereof, and the compound has obvious inhibition on DHODH. The blocking effect can be used as DHODH specific inhibitor, can be used for preparing medicines for treating diseases caused by fungal infection, can be used for preparing agricultural fungicides, and has wide application prospects.
- -
-
Paragraph 0134-0138
(2021/09/26)
-
- WEE1 inhibitors as well as preparation and application thereof
-
The invention relates to WEE1 inhibitors as well as preparation and application thereof. The present invention relates to compounds of formula (I), or pharmaceutically acceptable salts, solvates, polymorphs or isomers thereof, and their use in the preparation of medicaments for the treatment of diseases associated with WEE1 activity.
- -
-
Paragraph 0215-0221; 0411-0417
(2020/10/14)
-
- Discovery and SARs of 5-Chloro- N4-phenyl- N2-(pyridin-2-yl)pyrimidine-2,4-diamine Derivatives as Oral Available and Dual CDK 6 and 9 Inhibitors with Potent Antitumor Activity
-
Cyclin-dependent kinases (CDKs) are promising therapeutic targets for cancer therapy. Herein, we describe our efforts toward the discovery of a series of 5-chloro-N4-phenyl-N2-(pyridin-2-yl)pyrimidine-2,4-diamine derivatives as dual CDK6 and 9 inhibitors. Intensive structural modifications lead to the identification of compound 66 as the most active dual CDK6/9 inhibitor with balancing potency against these two targets and good selectivity over CDK2. Further biological studies revealed that compound 66 was directly bound to CDK6/9, resulting in suppression of their downstream signaling pathway and inhibition of cell proliferation by blocking cell cycle progression and inducing cellular apoptosis. More importantly, compound 66 significantly inhibited tumor growth in a xenograft mouse model with no obvious toxicity, indicating the promising therapeutic potential of CDK6/9 dual inhibitors for cancer treatment. Therefore, the above results are of great importance in the development of dual CDK6/9 inhibitors for cancer therapy.
- Wang, Yang,Chen, Xing,Yan, Yaoyao,Zhu, Xiaochen,Liu, Mingming,Liu, Xinhua
-
p. 3327 - 3347
(2020/04/08)
-
- Design, synthesis and biological evaluation of novel osthole-based derivatives as potential neuroprotective agents
-
A total of 26 compounds based on osthole skeleton were designed, synthesized. Their cytoprotective abilities of antioxidation, anti-inflammation and Aβ42(Amyloid β-protein 42)-induced neurotoxicity were evaluated by MTT assays. Mechanism of the action of selected compounds were investigated by molecular docking. AlogP, logS and blood–brain barrier (BBB) permeability of all these compounds were simulated by admetSAR. Most of the compounds showed better antioxidative and anti-inflammatory activities compared with osthole, especially OST7 and OST17. The compound OST7 showed relative high activity in neuroprotection against H2O2 (45.7 ± 5.5%), oxygen glucose deprivation (64.6 ± 4.8%) and Aβ42 (61.4 ± 5.2%) at a low concentration of 10 μM. EC50 of selected compounds were measured in both H2O2 and OGD induced cytotoxicity models. Moreover, NO inhibiting ability of OST17(50.4 ± 7.1%) already surpassed the positive drug indomethacin. The structure activity relationship study indicated that introduction of piperazine group, tetrahydropyrrole group and aromatic amine group might be beneficial for enhancement of osthole neuroprotective properties. Molecular docking explained that the reason OST7 exhibited relatively stronger neuroprotection against Aβ because of the greater area of interactions between molecule and target protein. OST7 and OST17 both provided novel methods to investigate osthole as anti-AD drugs.
- Zhang, Li,Wu, Yuhang,Yang, Guixiang,Gan, Haixian,Sang, Dayong,Zhou, Jiye,Su, Lin,Wang, Rui,Ma, Lei
-
supporting information
(2020/11/03)
-
- METHOD OF TREATING COCCIDIOIDES INFECTION
-
The invention relates to the therapeutic use of olorofim, 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2-oxoacetamide in the prevention and treatment of a fungal infection caused by a Coccidioides species.
- -
-
Paragraph 0200; 0213-0214
(2020/11/10)
-
- HETEROCYCLIC COMPOUNDS AND USES THEREOF
-
Heterocyclic compounds as Wee1 inhibitors are provided. The compounds may find use as therapeutic agents for the treatment of diseases and may find particular use in oncology.
- -
-
Paragraph 0334-0336
(2019/04/25)
-
- Phenylpiperazine type UBE2F small molecule inhibitor and synthesis method thereof
-
The invention discloses a phenylpiperazine type UBE2F small molecule inhibitor and a synthesis method thereof, discloses a phenylpiperazine type compound represented by the general formula I or a pharmaceutically acceptable salt thereof, and further discloses a synthesis route of the general formula I and a synthesis method of each step. As a small molecule inhibitor target at UBE2F, that phenylpiperazine type compound of the present invention effectively suppresses the growth of tumor cell by preventing the G2/M process of cell cycle and inducing apoptosis of human tumor cells. Therefore, thecompound is a new class of specific anti-tumor drugs by targeting UBE2F.
- -
-
Paragraph 0034-0035; 0038-0039
(2019/09/14)
-
- ANTI-FUNGAL TREATMENT
-
Provided are compounds, methods, and pharmaceutical compositions useful for treatment of fungal infections, e.g., aspergillosis, candidiasis, cryptococcosis, histoplasmosis, and the like. For example, the pharmaceutical composition may include a pharmaceutically acceptable carrier or excipient, and a compound represented by Ar— C(=NR1)NR2— A---X— Y— Het2 and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted aryl or nitrogen- containing heteroaryl. R1 and R2 may independently be H, optionally substituted C1-C6 aikyi, or optionally substituted C3-C6 cyeloalkyi. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cyeloalkyi, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C10 alkyi or optionally substituted C2-C10 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.
- -
-
Paragraph 00133
(2018/03/25)
-
- ANTI-PARASITIC COMPOUNDS
-
Provided are compounds, methods, and pharmaceutical compositions useful for treatment of parasites, e.g., Leishmania. For example, the compound may he represented by Ar—C(=NR1)NR2—A—X—Y—Het2, and pharmaceutically acceptable salts thereof. Ar may be an optionally substituted, aryl or nitrogen-containing heteroaryl. R1 and R2 may independently represent H, optionally substituted C1-C6 alkyl, or optionally substituted C3-C6 cycloalkyl. A may be a bond or an optionally substituted linking moiety comprising 1, 2, or 3 rings. Each ring in the optionally substituted linking moiety may independently be one of: aryl, cycloalkyl, heterocycloalkyl, and heteroaryl. X may be O, S, amide, or a bond. Y may be optionally substituted C1-C14 alkyl or optionally substituted C2-C14 alkenyl. Het2 may be an optionally substituted five-membered nitrogen-containing heteroaromatic ring comprising 1, 2, or 3 ring heteroatoms.
- -
-
Paragraph 00158
(2018/03/25)
-
- Design, synthesis and antimycobacterial activity of novel imidazo[1,2-a]pyridine-3-carboxamide derivatives
-
We report herein the design and synthesis of “novel imidazo [1,2-a]pyridine-3-carboxamides (IPAs)” bearing a variety of different linkers, based on the structure of IMB-1402 discovered in our lab. Results reveal that 2,6-dimethyl-N-[2-(phenylamino)ethyl] IPAs with an electron-donating group on the benzene ring as a potent scaffold. Compounds 26g and 26h have considerable activity (MIC: 0.041–2.64 μM) against drug-sensitive/resistant MTB strains, and they have acceptable safety indices against MTB H37Rv with the SI values of 4395 and 1405, respectively. Moreover, N-[2-(piperazin-1-yl)ethyl] moiety was also identified as a potentially alternative linker (compound 31), opening a new direction for further SAR studies.
- Lv, Kai,Li, Linhu,Wang, Bo,Liu, Mingliang,Wang, Bin,Shen, Weiyi,Guo, Huiyuan,Lu, Yu
-
p. 117 - 125
(2017/06/05)
-
- PHARMACEUTICAL FORMULATION
-
A pharmaceutical composition suitable for oral administration comprising particles of 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2-oxoacetamide is provided. Also provided is a pharmaceutical composition suitable for parenteral administration wherein the composition comprises 2-(1,5-dimethyl- 3-phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2-oxoacetamide. The compositions are useful in the treatment of fungal infection in a subject in need thereof.
- -
-
Page/Page column 30; 33; 34
(2017/12/29)
-
- Electrophilic Zinc Homoenolates: Synthesis of Cyclopropylamines from Cyclopropanols and Amines
-
Metal homoenolates, produced via C-C bond cleavage of cyclopropanols, have been extensively investigated as nucleophiles for the synthesis of β-substituted carbonyl derivatives. Herein, we demonstrate that zinc homoenolates can react as carbonyl-electrophiles in the presence of nucleophilic amines to yield highly valuable trans-cyclopropylamines in good yields and high diastereoselectivities. GSK2879552, a lysine demethylase 1 inhibitor currently in clinical trials for the treatment of small cell lung carcinoma, was synthesized using this strategy.
- Mills, L. Reginald,Barrera Arbelaez, Luis Miguel,Rousseaux, Sophie A. L.
-
supporting information
p. 11357 - 11360
(2017/08/30)
-
- Pd-Catalyzed Synthesis of Piperazine Scaffolds under Aerobic and Solvent-Free Conditions
-
A facile Pd-catalyzed methodology providing an efficient synthetic route to biologically relevant arylpiperazines under aerobic conditions is reported. Electron donating and sterically hindered aryl chlorides were aminated to afford yields up to 97%, with examples using piperazine as solvent, illustrating an ecofriendly, cost-effective synthesis of these privileged structures.
- Reilly, Sean W.,Mach, Robert H.
-
supporting information
p. 5272 - 5275
(2016/10/31)
-
- ANTIFUNGAL AGENTS
-
The invention provides a pyrrole compound, which compound is (a)2-(1,5-dimethyl-3- phenyl-1H-pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2- oxoacetamideor a deuterated derivative thereof, or(b)2-(1,5-dimethyl-3-phenyl-1H-pyrrol- 2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)-3-hydroxyphenyl)-2-oxoacetamide or a deuterated derivative thereof, or (c) a prodrug of compound (a) or a prodrug of compound (b), or a pharmaceutically acceptable salt or agriculturally acceptable salt of (a), (b) or (c). Also provided are combinations and compositions comprising the compound and known antifungal agents. The invention also relates to the therapeutic use of a compound of the invention in prevention or treatment of fungal diseases. It also relates to the use of:2-(1,5-dimethyl-3-phenyl-1H- pyrrol-2-yl)-N-(4-(4-(5-fluoropyrimidin-2-yl)piperazin-1-yl)phenyl)-2-oxoacetamide or an agriculturally acceptable salt thereof, or 2-(1,5-dimethyl-3-phenyl-1H-pyrrol-2-yl)-N-(4-(4- (5-fluoropyrimidin-2-yl)piperazin-1-yl)-3-hydroxyphenyl)-2-oxoacetamide or an agriculturally acceptable salt thereof, as an agricultural fungicide.
- -
-
Page/Page column 34-35
(2016/06/21)
-
- Chrysin-piperazine conjugates as antioxidant and anticancer agents
-
Synthesis of 7-(4-bromobutoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one intermediate treating chrysin with 1,4-dibromobutane facilitated combination of chrysin with a wide range of piperazine moieties which were equipped via reacting the corresponding amines with bis(2-chloroethyl)amine hydrochloride in diethylene glycol monomethyl ether solvent. Free radical scavenging potential of prepared products was analyzed in vitro adopting DPPH and ABTS bioassay in addition to the evaluation of in vitro anticancer efficacies against cervical cancer cell lines (HeLa and CaSki) and an ovarian cancer cell line SK-OV-3 using SRB assay. Bearable toxicity of 7a-w was examined employing Madin-Darby canine kidney (MDCK) cell line. In addition, cytotoxic nature of the presented compounds was inspected utilizing Human bone marrow derived mesenchymal stem cells (hBM-MSCs). Overall, 7a-w indicated remarkable antioxidant power in scavenging DPPH+ and ABTS++, particularly analogs 7f, 7j, 7k, 7l, 7n, 7q, 7v, 7w have shown promising free radical scavenging activity. Analogs 7j and 7o are identified to be highly active candidates against HeLa and CaSki cell lines, whereas 7h and 7l along with 7j proved to be very sensitive towards ovarian cancer cell line SKOV-3. None of the newly prepared scaffolds showed cytotoxic nature toward hBM-MSCs cells. From the structure-activity point of view, nature and position of the electron withdrawing and electron donating functional groups on the piperazine core may contribute to the anticipated antioxidant and anticancer action. Different spectroscopic techniques (FT-IR, 1H NMR, 13C NMR, Mass) and elemental analysis (CHN) were utilized to confirm the desired structure of final compounds.
- Patel, Rahul V.,Mistry, Bhupendra,Syed, Riyaz,Rathi, Anuj K.,Lee, Yoo-Jung,Sung, Jung-Suk,Shinf, Han-Seung,Keum, Young-Soo
-
p. 166 - 177
(2016/05/24)
-
- An integrated flow and microwave approach to a broad spectrum protein kinase inhibitor
-
The protein kinase inhibitor CTx-0152960 (6, 2-((5-chloro-2-((4-morpholinophenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide), and the piperazinyl analogue, CTx-0294885 (7, 2-((5-chloro-2-((4-piperazin-1-ylphenyl)amino)pyrimidin-4-yl)amino)-N-methylbenzamide), were prepared using a hybrid flow and microwave approach. The use of flow chemistry approaches avoided the need for Boc-protection of piperidine in the key SNAr coupling with 1-fluoro-4-nitrobenzene. Microwave coupling of 4-morphilinoaniline 8 and 4-(piperazine-1-yl)aniline 9 with 2-(2,5-dichloropyrimidine-4-ylamino)-N-methylbenzamide 10, proved to be the most efficacious route to the target analogues 6 and 7. This hybrid methodology reduced the number of synthetic steps, gave enhanced overall yields and increased atom economy through step reduction and minimal requirement for chromatographic purification, relative to the original batch synthesis approach.
- Russell, Cecilia,Lin, Andrew J. S.,Hains, Peter,Simone, Michela I.,Robinson, Phillip J.,Mccluskey, Adam
-
p. 93433 - 93437
(2015/11/17)
-
- HETEROCYCLIC COMPOUNDS AND USES THEREOF
-
The present invention relates to pharmaceutical compounds, compositions and methods, especially as they are related to compositions and methods for the treatment and/or prevention of a proliferation disorder, a cancer, a tumor, an inflammatory disease, an autoimmune disease, psoriasis, dry eye or an immunologically related disease, and in some embodiments diseases or disorders related to the dysregulation of kinase such as, but not limited to, EGFR (including HER), Alk, PDGFR, BLK, BMX/ETK, FLT3(D835Y), ITK, TEC, TXK, BTK, or JAK, and the respective pathways.
- -
-
Paragraph 00285
(2015/02/02)
-
- Structure-activity relationship study of E6 as a novel necroptosis inducer
-
Necroptosis inducers represent a promising potential treatment for drug-resistant cancer. We herein describe the structure modification of E6, which was identified recently as a potent and selective necroptosis inducer. The studies described herein demonstrate for the first time that functionalized biphenyl derivatives possess necroptosis inducer activity. Furthermore, these studies have led to the identification of two promising compounds (5h and 5j) that can be used for further optimization studies as well as mechanism of action investigations.
- Mou, Jianfeng,Park, Ann,Cai, Yu,Yuan, Junying,Yuan, Chengye
-
supporting information
p. 3057 - 3061
(2015/06/22)
-
- 2, 4 -DIAMINOPYRIMIDINE DERIVATIVES AS PROTEIN KINASE INHIBITORS
-
The present invention relates to novel pyrimide derivatives of formula (I): that are useful as kinase inhibitors. More particularly, the present invention relates to novel pyrimidine compounds, methods for their preparation, pharmaceutical compositions containing these compounds and uses of these compounds in the treatment of proliferative disorders.
- -
-
Page/Page column 118
(2012/05/20)
-
- 4-Substituted-2-phenylquinazolines as inhibitors of BCRP
-
We investigated several 2-phenylquinazolines with different substitutions at position 4 for their BCRP inhibition. Compounds with phenyl ring attached via an amine-containing linker at position 4 were found to be potent inhibitors of BCRP. In general compounds with meta substitution of phenyl ring at position 4 were found to have higher inhibitory effect, compound 12 being the most potent and selective towards BCRP.
- Juvale, Kapil,Wiese, Michael
-
p. 6766 - 6769,4
(2012/12/12)
-
- Novel benzo[ b ]thiophene derivatives as new potential antidepressants with rapid onset of action
-
We report benzo[b]thiophene derivatives synthesized according to a dual strategy. 8j, 9c, and 9e with affinity values toward 5-HT7R and 5-HTT were selected to probe their antidepressant activity in vivo using the forced swimming text (FST). The results showed significant antidepressant activity after chronic treatment. 9c was effective in reducing the immobility time in FST even after acute treatment. These findings identify these compounds as a new class of antidepressants with a rapid onset of action.
- Berrade, Luis,Aisa, Bárbara,Ramirez, María J.,Galiano, Silvia,Guccione, Salvatore,Moltzau, Lise Román,Levy, Finn Olav,Nicoletti, Ferdinando,Battaglia, Giuseppe,Molinaro, Gemma,Aldana, Ignacio,Monge, Antonio,Perez-Silanes, Silvia
-
supporting information; experimental part
p. 3086 - 3090
(2011/07/07)
-
- 2-OXO-2- (2-PHENYL-5,6,7,8-TETRAHYDRO-INDOLIZIN-3-YL) -ACETAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ANTIFUNGAL AGENTS
-
The invention provides compounds of formula (I), and pharmaceutically and agriculturally acceptable salts thereof: wherein: R1, R2, R3, R4, R5, R6, R7, R8, A1, L1 and n are as defined herein. These compounds and their pharmaceutically acceptable salts are useful in the manufacture of medicaments for use in the prevention or treatment of a fungal disease. Compounds of formula (I), and agriculturally acceptable salts thereof, may also be used as agricultural fungicides.
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-
Page/Page column 16-17
(2011/02/15)
-
- QUATERNARY AMMONIUM SALT COMPOUNDS OF SPIROCYCLOPIPERAZINES, PREPARATION METHODS AND USES THEREOF
-
Compounds represented by general formula (I), their stereoisomers, tautomers, derivatives, prodrugs or pharmaceutically acceptable salts, and their preparation methods or uses for the manufacture of a medicament of analgesics. In which R1 is selected from H, substituted or unsubstituted phenyl, or substituted or unsubstituted heteroaryl; A is bond, or saturated or unsaturated straight-chain or branched-chain hydrocarbon radical; R2, R3 are each independently hydrogen or methyl, which linked with any position of spirocyclo-structure; n and m are each independently integer between 0-2, do not represent 0 at the same time; B and D are each independently C1-C3 straight-chain or branched-chain alkylene; Y is selected from -CHR4-, O, S, -S(O)-, -SO2-, -NR4- and substituted or unsubstituted phenylene, in which R4 represents H, C1-C6 saturated or unsaturated alkyl, methyl or ethyl substituted by substituted or unsubstituted aryl or heteroaryl; and X- is pharmaceutical acceptable organic or inorganic anion. These compounds can be used as muscarine receptor (M-receptor) and/or nicotine acetylcholine receptor (N-receptor) agonist or antagonist. These compounds have good analgesic effect without side effect such as addiction.
- -
-
Page/Page column 11-12
(2009/04/23)
-
- Discovery and Initial SAR of Arylsulfonylpiperazine Inhibitors of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)
-
High-throughput screening of a small-molecule compound library resulted in the identification of a series of arylsulfonylpiperazines that are potent and selective inhibitors of human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1). Optimization of the initial lead resulted in the discovery of compound (R)-45 (11β-HSD1 IC50 = 3 nM).
- Sun, Daqing,Wang, Zhulun,Di, Yongmei,Jaen, Juan C.,Labelle, Marc,Ma, Ji,Miao, Shichang,Sudom, Athena,Tang, Liang,Tomooka, Craig S.,Tu, Hua,Ursu, Stefania,Walker, Nigel,Yan, Xuelei,Ye, Qiuping,Powers, Jay P.
-
scheme or table
p. 3513 - 3516
(2009/04/11)
-
- CHROMAN COMPOUNDS AS 5-HT1B ANTAGONISTS
-
Chroman derivatives according to formula (I), wherein R1, R2, R3 and R4 are as defined in the specification, pharmaceutically-acceptable salts, methods of making, pharmaceutical compositions containing and methods for using the same. The compounds are 5-HT1B antagonists and are useful in the treatment of mood and anxiety disorders .as well as cognitive disorders.
- -
-
Page/Page column 52
(2008/06/13)
-
- Unique spirocyclopiperazinium salt III: Further investigation of monospirocyclopiperazinium (MSPZ) salts as potential analgesics
-
Two novel classes of monospirocyclopiperazinium salts were designed, synthesized, and evaluated for their in vivo analgesic activities. Some interesting structure-activity relationships are revealed: (1) Spirocyclopiperazinium moiety is favorable to improve the analgesic activity; (2) The size and conformation of spirocyclopiperazinium moiety significantly affects the analgesic activity; (3) Phenylethyl group of 3d is a crucial pharmacophore. Among the compounds synthesized, 3d exhibited the most potent activity with low toxicity. Further antinociceptive mechanism studies of 3d showed that these compounds will be a new kind of analgesics.
- Sun, Qi,Yue, Cai-Qin,Ye, Jia,Li, Chang-Ling,Cheng, Tie-Ming,Li, Run-Tao
-
p. 6245 - 6249
(2008/04/07)
-
- Synthesis and biological evaluation of benzopyran analogues bearing class III antiarrhythmic pharmacophores
-
We have synthesized a series of compounds combining the hydroxy-benzopyran ring of vitamin E with the methylsulfonylaminophenyl group of class III antiarrhythmic drugs, connected through tertiary amine moieties. Evaluation of the antiarrhythmic and antioxidant activity of the new compounds was carried out on isolated rat heart preparations using the non-recirculating Langendorff mode. The new analogues were present, at 10 μM concentration, during ischemia and reperfusion. Selected compounds were further studied by a conventional microelectrode method in order to get insight into their cellular mode of action. The most active compound, N-[4-[2-[[2-(3,4-dihydro-6-hydroxy-2,2,7,8-tetramethyl-2H-1-benzopyran-5 -yl)ethyl] methylamine]ethyl]phenyl]methanesulfonamide (19a), reduces premature beats, prolongs QT and QRS intervals during ischemia and reperfusion, and reduces MDA content, leading to a fast recovery of the heart. In addition, it exhibits moderate class III antiarrhythmic action.
- Koufaki, Maria,Kiziridi, Christina,Papazafiri, Panagiota,Vassilopoulos, Athanasios,Varro, Andras,Nagy, Zsolt,Farkas, Attila,Makriyannis, Alexandros
-
p. 6666 - 6678
(2007/10/03)
-
- Parallel synthesis of N-arylpiperazines using polymer-assisted reactions
-
A series of N-arylpiperazines were prepared in a parallel fashion using palladium-catalyzed cross-coupling, or nucleophilic aromatic displacement chemistries, and polymer-assisted sequestration and purification techniques as key steps.
- Duncton, Matthew A. J.,Roffey, Jonathan R. A.,Hamlyn, Richard J.,Adams, David R.
-
p. 2549 - 2552
(2007/10/03)
-
- A general and convenient synthesis of N-aryl piperazines
-
A general and convenient synthesis of N-aryl piperazines from bis(2-chloroethyl)amine hydrochloride and a broad range of anilines in diethylene glycol monomethyl ether is described.
- Liu, Kevin G.,Robichaud, Albert J.
-
p. 7921 - 7922
(2007/10/03)
-
- Tetracyclic benzimidazole derivatives and combinatorial libraries thereof
-
The present invention relates to novel tetracyclic benzimidazole derivative compounds of the following formula: wherein R1to R10have the meanings described in here. The invention further relates to combinatorial libraries containing two or more such compounds, as well as methods of preparing tetracyclic benzimidazole derivative compounds.
- -
-
-
- Sequential mono-N-arylation of piperazine nitrogens. Part 1: A simplified method and its application to the preparation of a key N,N'-biaryl piperazine antifungal intermediate
-
A simple sequential N-arylation of piperazine without the use of a protecting group, catalyst, specialized equipment or a large excess of piperazine, and its application towards the preparation of the key differentially N,N'-biarylated piperazine antifungal intermediate N-(4-hydroxyphenyl)-N'-(4-aminophenyl)piperazine, 6, is described.
- Hepperle, Michael,Eckert, Jeffrey,Gala, Dinesh
-
p. 5655 - 5659
(2007/10/03)
-
- Sequential mono-N-arylation of piperazine nitrogens. Part 2: The role of hydrogen bonding
-
A mechanistic study of the simple sequential N-arylation of piperazine suggests that in an electron-withdrawing group (EWG) containing N-arylated piperazines, hydrogen bonding of the secondary amine hydrogen is important for its non-metal catalyzed conversion to N,N'-diaryl piperazines. A combination of synthetic experiments, molecular modeling, and NMR studies were carried out to test this hypothesis.
- Eckert, Jeffrey,Chan, Tze-Ming,Osterman, Rebecca M.,Lambert, Joseph B.,Gala, Dinesh
-
p. 5661 - 5665
(2007/10/03)
-
- Scavenger assisted combinatorial process for preparing libraries of amides, carbamates and sulfonamides
-
This invention relates to a novel solution phase process for the preparation of amide, carbamate, and sulfonamide combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
- -
-
-
- Solution phase combinatorial synthesis of arylpiperazines
-
A solution phase combinatorial synthesis of aryl piperazines 1 and 2 is described based on the S(N)Ar reaction and Schotten-Baumann acylation. The use of excess reagent is allowed and pure arylpiperazines 1 and 2 were obtained by simple acid/base washing.
- Neuville, Luc,Zhu, Jieping
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p. 4091 - 4094
(2007/10/03)
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- Antiviral agents
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Antiviral compounds (I): the symbols being as defined in the specification, are efficacious against infections caused by a variety of DNA viruses, RNA viruses and retroviruses. Other specified compounds also exhibit activity. The compounds have a wider spectrum of activity than known antiviral substances.
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- Series of 5-[-(4-aryl-1-piperazinyl)alkyl]-2-oxazolidinone derivatives useful in the treatment of allergic conditions
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A method of treating allergic disorders and pharmaceutical compositions therefore are disclosed for a series of 5-[(4-aryl-1-piperazinyl)alkyl]-2-oxazolidinone derivatives of Formula I. These compounds are useful in inhibiting Type I allergic STR1 responses in a living animal and thus can be used to treat allergic phenomena such as asthma, rhinitis, atopic dermatitis, chronic hives, allergic conjunctivitis and the like.
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- Pyrimidinedione compounds, method of producing the same and antiarrythmic agents containing the same
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A pyrimidinedione derivative compound has a basic backbone in which a phenyl group part and a pyrimidinedione part are linked by a structure comprising an alkyl chain containing at least two nitrogen atoms. The pyrimidinedione derivative is useful for a medical treatment of cardiac arrhythmias.
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- Studies in Potential Filaricides: Part XV - Synthesis of 1-Acyl/Aryl-4-substituted-piperazines as Diethylcarbamazine Analogs
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1-Acyl-4-substituted-piperazines (4-29) have been prepared starting from 1-benzylpiperazine while 1-aryl-4-aroylpiperazines (30-44) have been obtained from the corresponding 1-arylpiperazines.None of the compounds shows any significant filaricidal activity against Litomosoides carinii in cotton rats and cestodicial activity against Hymenolepis nana in mice.
- Agrawal, V. K.,Sharma, Satyavan
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p. 650 - 654
(2007/10/02)
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