- Synthesis of 2,3-dimethylthio-6-pyridyl tetrathiafulvalene: A precursor for a new system involving a direct linkage between a strong donor (D) and a strong acceptor (A)
-
A multi-step synthesis of a novel tetrathiafulvalene derivative involving a 4-pyridyl substituent directly attached to the TTF moiety is described.
- Paz-Tal Levi, Ofra,Becker, James Y.,Ellern, Arkady,Khodorkovsky, Vladimir
-
-
Read Online
- MULTI-STIMULI RESPONSIVE METAL-ORGANIC FRAMEWORKS
-
This invention relates to multi-stimuli responsive metal-organic frameworks (MOFs) comprising a repeat unit of the formula M2(L1)2(L2)2. Also disclosed are methods of preparation of multi-stimuli responsive MOFs of the formula M2(L1)2(L2)2 as well as their uses.
- -
-
Page/Page column 66; 67
(2021/12/08)
-
- Design, synthesis, and biological evaluation of urea-based ROCK2 inhibitors
-
A series of urea-based ROCK2 inhibitors were design and synthesized. The inhibitory activity on ROCK2 was screened by enzyme-linked immunosorbent assay (ELISA). The study results showed that the urea derivatives exhibited certain ROCK2 inhibitory activity. The most potent compound 10p showed ROCK2 inhibitory activity with the IC50?value of 0.03?μM. A preliminary structure-activity relationship was then summarized. The molecular docking studies showed that further optimization needs to conduct to obtain more potent ROCK inhibitors.
- Wang, Linan,Qi, Junhui,Fan, Meixia,Yao, Lei
-
p. 969 - 978
(2021/10/07)
-
- SELECTIVE LIGANDS OF HUMAN CONSTITUTIVE ANDROSTANE RECEPTOR
-
The present invention provides a structurally novel class of heterocyclic compounds of general formula I wherein L1 is heteroaryl and L2 is heteroaryl or aryl. The novel compounds are useful in a method of prevention or treatment of a condition which is m
- -
-
Page/Page column 81
(2020/11/12)
-
- SUBSTITUTED PYRAZOLO[4,3-b]PYRIDINES AND THEIR USE AS GLUN2B RECEPTOR MODULATORS
-
Substituted pyrazolo[4,3-b]pyridines as GluN2B receptor ligands. Such compounds may be used in GluN2B receptor modulation and in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by GluN2B rece
- -
-
Page/Page column 60
(2020/12/30)
-
- Studies on non-steroidal inhibitors of aromatase enzyme; 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives
-
Steroidal and non-steroidal aromatase inhibitors target the suppression of estrogen biosynthesis in the treatment of breast cancer. Researchers have increasingly focused on developing non-steroidal derivatives for their potential clinical use avoiding steroidal side-effects. Non-steroidal derivatives generally have planar aromatic structures attached to the azole ring system. One part of this ring system comprises functional groups that inhibit aromatization through the coordination of the haem group of the aromatase enzyme. Replacement of the triazole ring system and development of aromatic/cyclic structures of the side chain can increase selectivity over aromatase enzyme inhibition. In this study, 4-(aryl/heteroaryl)-2-(pyrimidin-2-yl)thiazole derivatives were synthesized and physical analyses and structural determination studies were performed. The IC50 values were determined by a fluorescence-based aromatase inhibition assay and compound 1 (4-(2-hydroxyphenyl)-2-(pyrimidine-2-yl)thiazole) were found potent inhibitor of enzyme (IC50:0.42 nM). Then, their antiproliferative activity over MCF-7 and HEK-293 cell lines was evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Compounds 1, 7, 8, 13, 15, 18, 21 were active against MCF-7 breast cancer cells. Lastly, a series of docking experiments were undertaken to analyze the crystal structure of human placental aromatase and identify the possible interactions between the most active structure and the active site.
- Sahin, Zafer,Ertas, Merve,Berk, Bark?n,Biltekin, Sevde Nur,Yurttas, Leyla,Demirayak, Seref
-
p. 1986 - 1995
(2018/03/12)
-
- Substituted N-Phenyl-5-(2-(phenylamino)thiazol-4-yl)isoxazole-3-carboxamides Are Valuable Antitubercular Candidates that Evade Innate Efflux Machinery
-
Tuberculosis remains one of the deadliest infectious diseases in the world, and the increased number of multidrug-resistant and extremely drug-resistant strains is a significant reason for concern. This makes the discovery of novel antitubercular agents a cogent priority. We have previously addressed this need by reporting a series of substituted 2-aminothiazoles capable to inhibit the growth of actively replicating, nonreplicating persistent, and resistant Mycobacterium tuberculosis strains. Clues from the structure-activity relationships lining up the antitubercular activity were exploited for the rational design of improved analogues. Two compounds, namely N-phenyl-5-(2-(p-tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 7a and N-(pyridin-2-yl)-5-(2-(p-tolylamino)thiazol-4-yl)isoxazole-3-carboxamide 8a, were found to show high inhibitory activity toward susceptible M. tuberculosis strains, with an MIC90 of 0.125-0.25 μg/mL (0.33-0.66 μM) and 0.06-0.125 μg/mL (0.16-0.32 μM), respectively. Moreover, they maintained good activity also toward resistant strains, and they were selective over other bacterial species and eukaryotic cells, metabolically stable, and apparently not susceptible to the action of efflux pumps.
- Azzali, Elisa,Machado, Diana,Kaushik, Amit,Vacondio, Federica,Flisi, Sara,Cabassi, Clotilde Silvia,Lamichhane, Gyanu,Viveiros, Miguel,Costantino, Gabriele,Pieroni, Marco
-
p. 7108 - 7122
(2017/09/07)
-
- Synthesis method of ceftaroline fosamil intermediate 4-(4'-pyridyl)-1,3-thiazolyl-2-thiol
-
The invention discloses a synthesis method of an important antibiotic ceftaroline fosamil intermediate 4-(4'-pyridyl)-1,3-thiazolyl-2-thiol. The method comprises the following steps: carrying out Claisen condensation reaction on ethyl isonicotinate and ethyl acetate under alkaline conditions, carrying out acidic hydrolysis for decarboxylation, carrying out bromination reaction on the hydrolysis product and bromine, carrying out cyclization on the bromination product and ammonium dithiocarbamate, and finally, refluxing the cyclization product in glacial acetic acid to obtain the corresponding 4-(4'-pyridyl)-1,3-thiazolyl-2-thiol. The method has the advantages of fewer synthesis steps, low cost, cheap and accessible materials and low pollution, and is beneficial to industrial production.
- -
-
Paragraph 0011
(2016/11/24)
-
- 2-mercapto-4-pyridyl thiazole synthesis method (by machine translation)
-
The invention discloses a synthesis method of 2-sulfydryl-4-pyridyl thiazole. According to the technical scheme, 4-acetylpyridine serving as a raw material has a bromination reaction, and then ammonium dithiocarbamate is directly added to for reaction to obtain the 2-sulfydryl-4-pyridyl thiazole. The method is simple, efficient and mild in conditions, the intermediate is a bromide, the target product can be obtained by a one-pot process without purification, and the harm of the intermediate to a human body can be greatly reduced; and moreover, the obtained product is high in purity and yield and very suitable for industrial production.
- -
-
Paragraph 0023; 0024
(2017/04/08)
-
- Novel arylalkenylpropargylamines as neuroprotective, potent, and selective monoamine oxidase B inhibitors for the treatment of Parkinson's disease
-
To develop novel neuroprotective agents, a library of novel arylalkenylpropargylamines was synthesized and tested for inhibitory activities against monoamine oxidases. From this, a number of highly potent and selective monoamine oxidase B inhibitors were identified. Selected compounds were also tested for neuroprotection in in vitro studies with PC-12 cells treated with 6-OHDA and rotenone, respectively. It was observed that some of the compounds tested yielded a marked increase in survival in PC-12 cells treated with the neurotoxins. This indicates that these propargylamines are able to confer protection against the effects of the toxins and may also be considered as novel disease-modifying anti-Parkinsonian agents, which are much needed for the therapy of Parkinson's disease.
- Huleatt, Paul B.,Khoo, Mui Ling,Chua, Yi Yuan,Tan, Tiong Wei,Liew, Rou Shen,Balogh, Balázs,Deme, Ruth,G?l?ncsér, Flóra,Magyar, Kalman,Sheela, David P.,Ho, Han Kiat,Sperlágh, Beáta,Mátyus, Péter,Chai, Christina L. L.
-
supporting information
p. 1400 - 1419
(2015/03/04)
-
- Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors
-
The Rho kinases (ROCK1 and ROCK2) are highly homologous serine/threonine kinases that act on substrates associated with cellular motility, morphology, and contraction and are of therapeutic interest in diseases associated with cellular migration and contraction, such as hypertension, glaucoma, and erectile dysfunction. Beginning with compound 4, an inhibitor of ROCK1 identified through high-throughput screening, systematic exploration of SAR, and application of structure-based design, led to potent and selective ROCK inhibitors. Compound 37 represents significant improvements in inhibition potency, kinase selectivity, and CYP inhibition and possesses pharmacokinetics suitable for in vivo experimentation.
- Green, Jeremy,Cao, Jingrong,Bandarage, Upul K.,Gao, Huai,Court, John,Marhefka, Craig,Jacobs, Marc,Taslimi, Paul,Newsome, David,Nakayama, Tomoko,Shah, Sundeep,Rodems, Steve
-
p. 5028 - 5037
(2015/07/02)
-
- Diarylthiazole: An antimycobacterial scaffold potentially targeting PrrB-PrrA two-component system
-
Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE) >0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.
- Bellale, Eknath,Naik, Maruti,Vb, Varun,Ambady, Anisha,Narayan, Ashwini,Ravishankar, Sudha,Ramachandran, Vasanthi,Kaur, Parvinder,McLaughlin, Robert,Whiteaker, James,Morayya, Sapna,Guptha, Supreeth,Sharma, Sreevalli,Raichurkar, Anandkumar,Awasthy, Disha,Achar, Vijayshree,Vachaspati, Prakash,Bandodkar, Balachandra,Panda, Manoranjan,Chatterji, Monalisa
-
supporting information
p. 6572 - 6582
(2014/10/15)
-
- Structural design, synthesis and structure-activity relationships of thiazolidinones with enhanced anti-Trypanosoma cruzi activity
-
Pharmacological treatment of Chagas disease is based on benznidazole, which displays poor efficacy when administered during the chronic phase of infection. Therefore, the development of new therapeutic options is needed. This study reports on the structural design and synthesis of a new class of anti-Trypanosoma cruzi thiazolidinones (4 a-p). (2-[2-Phenoxy-1-(4-bromophenyl) ethylidene)hydrazono]-5-ethylthiazolidin-4-one (4 h) and (2-[2-phenoxy-1-(4- phenylphenyl)ethylidene)hydrazono]-5-ethylthiazolidin-4-one (4 l) were the most potent compounds, resulting in reduced epimastigote proliferation and were toxic for trypomastigotes at concentrations below 10 μM, while they did not display host cell toxicity up to 200 μM. Thiazolidinone 4 h was able to reduce the in vitro parasite burden and the blood parasitemia in mice with similar potency to benznidazole. More importantly, T. cruzi infection reduction was achieved without exhibiting mouse toxicity. Regarding the molecular mechanism of action, these thiazolidinones did not inhibit cruzain activity, which is the major trypanosomal protease. However, investigating the cellular mechanism of action, thiazolidinones altered Golgi complex and endoplasmic reticulum (ER) morphology, produced atypical cytosolic vacuoles, as well as induced necrotic parasite death. This structural design employed for the new anti-T. cruzi thiazolidinones (4 a-p) led to the identification of compounds with enhanced potency and selectivity compared to first-generation thiazolidinones. These compounds did not inhibit cruzain activity, but exhibited strong antiparasitic activity by acting as parasiticidal agents and inducing a necrotic parasite cell death. Stop the cycle! The attachment of an aryl ring to the iminic carbon produced thiazolidinones that are conformationally more restricted than first-generation thiazolidinones. This enhanced the potency of antiparasitic thiazolidinones, as observed under treatment with compound 4 h where parasite development and invasion in host cells were substantially reduced. Copyright
- Moreira, Diogo Rodrigo Magalhaes,Lima Leite, Ana Cristina,Cardoso, Marcos Verissimo Oliveira,Srivastava, Rajendra Mohan,Hernandes, Marcelo Zaldini,Rabello, Marcelo Montenegro,Da Cruz, Luana Faria,Ferreira, Rafaela Salgado,De Simone, Carlos Alberto,Meira, Cassio Santana,Guimaraes, Elisalva Teixeira,Da Silva, Aline Caroline,Dos Santos, Thiago Andre Ramos,Pereira, Valeria Rego Alves,Pereira Soares, Milena Botelho
-
supporting information
p. 177 - 188
(2014/01/17)
-
- Synthesis and biological evaluation of 2-aminothiazole derivatives as antimycobacterial and antiplasmodial agents
-
A series of compounds derived from the 2-amino-4-(2-pyridyl) thiazole scaffold was synthesized and tested for in vitro antimycobacterial activity against the Mycobacterium tuberculosis H37Rv strain, antiplasmodial activity against the chloroquine sensitive NF54 Plasmodium falciparum strain and cytotoxicity on a mammalian cell line. Optimal antimycobacterial activity was found with compounds with a 2-pyridyl ring at position 4 of the thiazole scaffold, a substituted phenyl ring at the 2-amino position, and an amide linker between the scaffold and the substituted phenyl. The antiplasmodial activity was best with compounds that had the phenyl ring substituted with hydrophobic electron withdrawing groups.
- Mjambili, Faith,Njoroge, Mathew,Naran, Krupa,De Kock, Carmen,Smith, Peter J.,Mizrahi, Valerie,Warner, Digby,Chibale, Kelly
-
supporting information
p. 560 - 564
(2014/01/23)
-
- Probing binding requirements of NAD kinase with modified substrate (NAD) analogues
-
Synthesis of novel NAD+ analogues that cannot be phosphorylated by NAD kinase is reported. In these analogues the C2′ hydroxyl group of the adenosine moiety was replaced by fluorine in the ribo or arabino configuration (1 and 2, respectively) or was inverted into arabino configuration to give compound 3. Compounds 1 and 2 showed inhibition of human NAD kinase, whereas analogue 3 inhibited both the human and Mycobacterium tuberculosis NAD kinase. An uncharged benzamide adenine dinucleotide (BAD) was found to be the most potent competitive inhibitor (Ki = 90 μM) of the human enzyme reported so far.
- Bonnac, Laurent,Chen, Liqiang,Pathak, Rashmi,Gao, Guangyao,Ming, Qian,Bennett, Eric,Felczak, Krzysztof,Kullberg, Martin,Patterson, Steven E.,Mazzola, Francesca,Magni, Giulio,Pankiewicz, Krzysztof W.
-
p. 1512 - 1515
(2007/10/03)
-
- Pyrrolidino-tetrahydroisoquinolines bearing pendant heterocycles as potent dual H3 antagonist and serotonin transporter inhibitors
-
A series of novel and potent 6-heteroaryl-pyrrolidino-tetrahydroisoquinolines with dual histamine H3 antagonist/serotonin transporter inhibitor activity is described. In vitro and in vivo data are discussed.
- Keith, John M.,Gomez, Leslie A.,Barbier, Ann J.,Wilson, Sandy J.,Boggs, Jamin D.,Lord, Brian,Mazur, Curt,Aluisio, Leah,Lovenberg, Timothy W.,Carruthers, Nicholas I.
-
p. 4374 - 4377
(2008/02/11)
-
- Mitotic kinesin inhibitors
-
The present invention relates to substituted thiazole derivatives that are useful for treating cellular proliferative diseases, for treating disorders associated with KSP kinesin and MCAK activity, and for inhibiting KSP kinesin and MCAK. The invention al
- -
-
Page/Page column 21
(2010/02/13)
-
- Drug efflux pump inhibitor
-
A medicament for preventive and/or therapeutic treatment of a microbial infection which comprises as an active ingredient a compound represented by the following general formula (I): wherein, R1 and R2 represent hydrogen atom, a halogen atom, hydroxyl group or the like, W1 represents —CH═CH—, —CH2O—, —CH2CH2— or the like; R3 represents hydrogen atom, a halogen atom, hydroxyl group or an amino group; R4 represents hydrogen atom, a group of —OZ0-4R5 (Z0-4 represents an alkylene group, a fluorine-substituted alkylene group or a single bond, and R5 represents a cyclic alkyl group, an aryl group or the like); W2 represents a single bond or —C(R8)═C(R9)— (R8 and R9 represent hydrogen atom, a halogen atom, a lower alkyl group or the like, Q represents an acidic group, but W2 and Q may together form vinylidenethiazolidinedione or an equivalent heterocyclic ring; m and n represent an integer of 0 to 2, and q represents an integer of 0 to 3.
- -
-
-
- DRUG DISCHARGE PUMP INHIBITORS
-
A medicament for preventive and/or therapeutic treatment of a microbial infection having an activity of eliminating resistance of a microorganism with acquired resistance to an antimicrobial agent, which comprises as an active ingredient a compound represented by the following general formula (I), a physiologically acceptable salt thereof, or a hydrate thereof: wherein R1 and R2 independently represent hydrogen atom, a halogen atom, carboxyl group and the like; J1 represents a 5- or 6-membered heteroaromatic ring; W1 represents -CH=CH-, -C≡C-, -CH2CH2- and the like; A1 represents phenylene group, pyridinediyl group, furandiyl group and the like; G1 represents oxygen atom, carbonyl group, ethynyl group and the like; p represents an integer of from 0 to 3; G2 represents phenylene group, furandiyl group, tetrahydrofurandiyl group and the like; G3 represents -CH2- or single bond; m and n represent an integer of 0 or 1; and Q1 represents an acidic group.
- -
-
-
