58012-34-3Relevant articles and documents
MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE
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Page/Page column 18; 20, (2019/06/23)
Provided are IDO1 inhibitor compounds of Formula (I) and pharmaceutically acceptable salts thereof, their pharmaceutical compositions, their methods of preparation, and methods for their use in the prevention and/or treatment of diseases.
INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE AND METHODS OF THEIR USE
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Paragraph 00190, (2018/03/25)
There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3 -dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.
Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer's Disease
Rabal, Obdulia,Sánchez-Arias, Juan A.,Cuadrado-Tejedor, Mar,De Miguel, Irene,Pérez-González, Marta,García-Barroso, Carolina,Ugarte, Ana,Estella-Hermoso De Mendoza, Ander,Sáez, Elena,Espelosin, Maria,Ursua, Susana,Haizhong, Tan,Wei, Wu,Musheng, Xu,Garcia-Osta, Ana,Oyarzabal, Julen
supporting information, p. 8967 - 9004 (2016/10/22)
Simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylases (HDAC) has recently been validated as a potentially novel therapeutic approach for Alzheimer's disease (AD). To further extend this concept, we designed and synthesized the first chemical series of dual acting PDE5 and HDAC inhibitors, and we validated this systems therapeutics approach. Following the implementation of structure- and knowledge-based approaches, initial hits were designed and were shown to validate our hypothesis of dual in vitro inhibition. Then, an optimization strategy was pursued to obtain a proper tool compound for in vivo testing in AD models. Initial hits were translated into molecules with adequate cellular functional responses (histone acetylation and cAMP/cGMP response element-binding (CREB) phosphorylation in the nanomolar range), an acceptable therapeutic window (>1 log unit), and the ability to cross the blood-brain barrier, leading to the identification of 7 as a candidate for in vivo proof-of-concept testing (Cuadrado-Tejedor, M.; Garcia-Barroso, C.; Sánchez-Arias, J. A.; Rabal, O.; Mederos, S.; Ugarte, A.; Franco, R.; Segura, V.; Perea, G.; Oyarzabal, J.; Garcia-Osta, A. Neuropsychopharmacology 2016, in press, doi: 10.1038/npp.2016.163).
IMMUNOREGULATORY AGENTS
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Paragraph 0416, (2016/06/01)
Compounds that modulate the oxidoreductase enzyme indoleamine 2,3- dioxygenase, and compositions containing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by indoleamine 2,3-dioxygenase is also provided.
IMMUNOREGULATORY AGENTS
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Paragraph 0471, (2016/06/01)
Compounds that modulate the oxidoreductase enzyme indoleamine 2,3- dioxygenase, and compositions containing the compounds, are described herein. The use of such compounds and compositions for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, that are mediated by indoleamine 2,3-dioxygenase is also provided.
BETA-LACTAMASE INHIBITORS
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Paragraph 00418, (2014/06/24)
Described herein are compounds and compositions that modulate the activity of beta-lactamases. In some embodiments, the compounds described herein inhibit beta-lactamase. In certain embodiments, the compounds described herein are useful in the treatment of bacterial infections.
NOVEL COMPOUNDS AS DUAL INHIBITORS OF PHOSPHODIESTERASES AND HISTONE DEACETYLASES
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Page/Page column 66, (2014/09/16)
It relates to certain compounds having a polycyclic structure and a hydroxamic acid moiety, wherein the polycyclic structure comprises at least three ring systems, wherein one ring system is a polycyclic ring system comprising from 2 to 4 rings; at least one ring is an aromatic ring; and wherein the structure comprises at least 3 nitrogen atoms and 1 oxygen atom. It also relates to a process for their preparation, as well as to pharmaceutical compositions containing them, and to their use in medicine, in particular in the treatment and/or prevention of neurological disorders coursing with a cognition deficit or impairment, or neurodegenerative diseases. wherein B1 is a radical selected from the group consisting of formula (A"), formula (B"), formula (C"), and formula (D"):
DIAZENIUMDIOLATE CYCLOHEXYL DERIVATIVES
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Page/Page column 25, (2011/12/04)
A compound having the structure (I) or a pharmaceutically acceptable salt thereof, wherein R3 is hydrogen, deuterium, —OH, —OC1-6alkyl, or halogen; R8 is hydrogen, deuterium, or C1-6alkyl; R11 and R12 are independently hydrogen, —C1-6alkyl, —OH, —OC1-6alkyl, or halogen; R13 and R14 are independently —C1-6alkyl, —(CH2)1-2OH, or —OC1-6alkyl, or, together with the nitrogen atom to which they are attached, form a 4- to 7-membered heterocyclic ring containing one nitrogen atom and 0 or 1 oxygen atoms, wherein said ring is unsubstituted or mono-, di- or tri-substituted with halogen or —C1-6alkyl; R15 is (CR1R2)nC(O)OR16, wherein n is 0, 1 or 2, —C(O)NHCH(R17)OR16, or —C(O)NHCH(R17)C(O)NHCH(R18)C(O)OR16; R16 is hydrogen, C1-6alkyl, or (CH2)1-2N+R19R20R21; R1, R2, R4, R5, R6, R7, R9, R10, R17, R18, R19, R20, and R21 are independently hydrogen or —C1-6alkyl; and stereoisomers thereof, and pharmaceutically acceptable salts thereof, and pharmaceutically acceptable salts of stereoisomers thereof
Comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4-trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron salts/phosphatidylcholine
Bousejra-El Garah, Fatima,Wong, Michael He-Long,Amewu, Richard K.,Muangnoicharoen, Sant,Maggs, James L.,Stigliani, Jean-Luc,Park, B. Kevin,Chadwick, James,Ward, Stephen A.,O'Neill, Paul M.
supporting information; scheme or table, p. 6443 - 6455 (2011/12/04)
Dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of synthetic antimalarial peroxides due to their structural simplicity, good stability, and impressive antimalarial activity. We investigated the reactivity of a series of potent amide functionalized tetraoxanes with Fe(II)gluconate, FeSO4, FeSO4/TEMPO, FeSO 4/phosphatidylcholine, and heme to gain knowledge of their potential mechanism of bioactivation and to compare the results with the corresponding 1,2,4-trioxolanes. Spin-trapping experiments demonstrate that Fe(II)-mediated peroxide activation of tetraoxanes produces primary and secondary C-radical intermediates. Reaction of tetraoxanes and trioxolanes with phosphatidylcholine, a predominant unsaturated lipid present in the parasite digestive vacuole membrane, under Fenton reaction conditions showed that both endoperoxides share a common reactivity in terms of phospholipid oxidation that differs with that of artemisinin. Significantly, when tetraoxanes undergo bioactivation in the presence of heme, only the secondary C-centered radical is observed, which smoothly produces regioisomeric drug derived-heme adducts. The ability of these tetraoxanes to alkylate the porphyrin ring was also confirmed with Fe IITPP and MnIITPP, and docking studies were performed to rationalize the regioselectivity observed in the alkylation process. The efficient process of heme alkylation and extensive lipid peroxidation observed here may play a role in the mechanism of action of these two important classes of synthetic endoperoxide antimalarial.
Identification of a 1,2,4,5-tetraoxane antimalarial drug-development candidate (RKA 182) with superior properties to the semisynthetic artemisinins
O'Neill, Paul M.,Amewu, Richard K.,Nixon, Gemma L.,ElGarah, Fatima Bousejra,Mungthin, Mathirut,Chadwick, James,Shone, Alison E.,Vivas, Livia,Lander, Hollie,Barton, Victoria,Muangnoicharoen, Sant,Bray, Patrick G.,Davies, Jill,Park, B. Kevin,Wittlin, Sergio,Brun, Reto,Preschel, Michael,Zhang, Kesheng,Ward, Stephen A.
scheme or table, p. 5693 - 5697 (2010/11/04)
(Figure Presented) Fighting drug resistence: From a library of over 150 1,2,4,5-tetraoxanes, the candidate RKA182 was selected for preclinical development as an antimalarial agent. RKA182 has outstanding in vitro activity against resistant strains of P. falciparum and retains this level of activity against southeast asian isolates that failed artemisinin-based combination therapy.
