81168-11-8Relevant articles and documents
Galantamine-curcumin hybrids as dual-site binding acetylcholinesterase inhibitors
Atanasova, Mariyana,Atanasova, Teodora,Doytchinova, Irini,Ivanov, Stefan,Konstantinov, Spiro,Lukarski, Atanas,Philipova, Irena,Stavrakov, Georgi,Zheleva, Dimitrina,Zhivkova, Zvetanka D.
, (2020/08/06)
Galantamine (GAL) and curcumin (CU) are alkaloids used to improve symptomatically neurodegenerative conditions like Alzheimer's disease (AD). GAL acts mainly as an inhibitor of the enzyme acetylcholinesterase (AChE). CU binds to amyloid-beta (Aβ) oligomers and inhibits the formation of Aβ plaques. Here, we combine GAL core with CU fragments and design a combinatorial library of GAL-CU hybrids as dual-site binding AChE inhibitors. The designed hybrids are screened for optimal ADME properties and BBB permeability and docked on AChE. The 14 best performing compounds are synthesized and tested in vitro for neurotoxicity and anti-AChE activity. Five of them are less toxic than GAL and CU and show activities between 41 and 186 times higher than GAL.
CLPX INHIBITORY COMPOUNDS FOR THE TREATMENT OF MULTI RESISTANT STAPHYLOCOCCUS AUREUS VIRULENCE AND FOR THE TREATMENT OF LEUKEMIA
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, (2018/07/26)
The present invention relates to antibiotic compounds and their use as ClpX inhibitors and in the treatment of bacterial infections, such as infections with multi-resistant Staphylococcus aureas, and in the treatment of leukemia. The present invention fur
6-AMINO-QUINOLINE-3-CARBONITRILS AS COT MODULATORS
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, (2017/01/26)
The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.
A Chemical Disruptor of the ClpX Chaperone Complex Attenuates the Virulence of Multidrug-Resistant Staphylococcus aureus
Fetzer, Christian,Korotkov, Vadim S.,Th?nert, Robert,Lee, Kyu Myung,Neuenschwander, Martin,von Kries, Jens Peter,Medina, Eva,Sieber, Stephan A.
, p. 15746 - 15750 (2017/10/20)
The Staphylococcus aureus ClpXP protease is an important regulator of cell homeostasis and virulence. We utilized a high-throughput screen against the ClpXP complex and identified a specific inhibitor of the ClpX chaperone that disrupts its oligomeric sta
CARBOXYLIC ACID DERIVATIVE AND SALT THEREOF
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Page 112-113, (2008/06/13)
The present invention provides a novel carboxylic acid compound, a salt thereof or a hydrate of them useful as an insulin sensitizer, and a medicament comprising the compound as an active ingredient. That is, the present invention provides a carboxylic acid compound represented by the following formula, a salt thereof, an ester thereof or a hydrate of them. Wherein R1 represents a hydrogen atom, hydroxyl group, halogen, carboxyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents; L represents a single bond, or a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group, each of which may have one or more substituents; M represents a single bond, or a C1-6 alkylene group, a C2-6 alkenylene group or a C2-6 alkynylene group, each of which may have one or more substituents; T represents a single bond, or a C1-3 alkylene group, a C2-3 alkenylene group or a C2-3 alkynylene group, each of which may have one or more substituents; W represents a carboxyl group;- - - represents a single bond etc. ; X represents a single bond, oxygen atom, a group represented by -NRX1CQ1O- (wherein Q1 represents an oxygen atom or sulfur atom; and RX1 represents a hydrogen atom, formyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents), -OCQ1NRX1- (wherein Q1 and RX1 are as defined above), -CQ1NRx1O- (wherein Q1 and RX1 are as def ined above), ONRX1CQ1- (wherein Q1 and RX1 are as defined above), - Q2SO2- (wherein Q2 is an oxygen atom or -NRX10- (wherein RX10 represents a hydrogen atom, formyl group, or a C1-6 alkyl group etc., each of which may have one or more substituents)) or -SO2Q2- (wherein Q2 is as defined above), (wherein, provided that RX2 and RX3, and/or RX4 and RX5 may together form a ring, Q3 and Q4 are the same as or different from each other and each represents an oxygen atom, (O)S(O) or NRX10 (wherein NRX10 is as defined above)); Y represents a 5- to 14-membered aromatic group etc., which may have one or more substituents and one or more hetero atoms; and the ring Z represents a 5-to 14-membered aromatic group which may have 0 to 4 substituents and one or more hetero atoms, and wherein part of the ring may be saturated.
4-[(4-(CARBOXYETHYL) PIPERIDINYL) METHYL] PYRROLIDINES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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Page 34; 26, (2010/02/07)
3-Substituted pyrrolidines having a 4-carboxypiperidinylmethyl substituent on the 4-position of the ring are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.
N-Acyl-l-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation
Chen, Li,Tilley, Jefferson,Trilles, Richard V.,Yun, Weiya,Fry, David,Cook, Charles,Rowan, Karen,Schwinge, Virginia,Campbell, Robert
, p. 137 - 140 (2007/10/03)
A series of N-benzylpyroglutamyl-l-phenylalanine derivatives bearing carbamoyl substituents in the 3- or 4-positions was prepared and assayed for inhibition of the interaction between VCAM and VLA-4. Potent inhibition was observed in a number of analogues with substitution in the 4-position favored over the 3-position. A crystal structure of the key intermediate 25 indicates that it accesses a low energy conformation which closely matches key pharmacophores of a structurally characterized cyclic peptide.
Development of dual-acting agents for thromboxane receptor antagonism and thromboxane synthase inhibition. 2. Design, synthesis, and evaluation of a novel series of phenyl oxazole derivatives
Takeuchi, Kumiko,Kohn, Todd J.,Mais, Dale E.,True, Timothy A.,Wyss, Virginia L.,Jakubowski, Joseph A.
, p. 1943 - 1948 (2007/10/03)
Synthesis and initial in vitro evaluation of a novel series of phenyl oxazole derivatives are described. An SAR study of the novel dual-acting TRA/TSI agent has revealed that the lipophilicity of the oxazole amide substituents greatly influences the TRA activity but not the TSI. The chain length of the alkenoic acid side chain affects both TRA and TSI. The optimal chain length for the combined activities was found to be n = 4 (heptenoic acid).
Synthesis of structural analogues of leukotriene B4 and their receptor binding activity
Konno, Mitoshi,Nakae, Takahiko,Sakuyama, Shigeru,Odagaki, Yoshihiko,Nakai, Hisao,Hamanaka, Nobuyuki
, p. 1621 - 1647 (2007/10/03)
Structural analogues of leukotriene B4 (LTB4) were designed based on the plausible conformation of LTB4 (1). Joining C-7-C-9 of the conformer A or B into an aromatic ring system led to the discovery of benzene analogues 2, 4 and 6a. Joining C-4-C-9 of the conformer C or D into an aromatic ring system led to the discovery of analogues 3, 5 and 7. The compounds examined in this study were evaluated as to their inhibition of [3H] LTB4 binding to human neutrophils, and by a secondary intact human neutrophil functional assay for agonist/antagonist activity. The first analogues prepared, compounds 2-7, demonstrated moderate potency in the LTB4, receptor binding assay. The modification of these compounds by the introduction of another substituent into the aromatic ring produced a marked increase in receptor binding (28c, IC50 = 0.020 μM; 38c, IC50 = 0.020 μM; 52a, IC50 = 0.020 μM; 52b, IC50 = 0.018 μM). Most of these structural analogues of LTB4 demonstrated agonist activity. Of the analogues prepared in this study, only compound 57 demonstrated weak LTB4 receptor antagonist activity, at 10 μM.
Bioactive hydroxyethylene dipeptide isosteres with hydrophobic (P3- P1)-moieties. A novel strategy towards small non-peptide renin inhibitors
Rasetti, Vittorio,Cohen, N. Claude,Rueeger, Heinrich,Goeschke, Richard,Maibaum, Juergen,Cumin, Frederic,Fuhrer, Walter,Wood, Jeanette M.
, p. 1589 - 1594 (2007/10/03)
The design and synthesis of new truncated δ-amino hydroxyethylene dipeptide isosteres lacking the P4-P2 peptide backbone is described. The most active compounds 15c and 30c inhibited human renin in the submicromolar range. This promising concept may offer the possibility to discover completely non-peptide, low-molecular weight renin inhibitors with improved pharmacokinetic properties.