37799-81-8Relevant articles and documents
Deciphering the robustness of pyrazolo-pyridine carboxylate core structure-based compounds for inhibiting α-synuclein in transgenic C. elegans model of Synucleinopathy
Hoda, Nasimul,Maqbool, Mudasir,Rajvansh, Roshani,Srividya, Kottapalli
, (2020)
Parkinson's disease (PD), a calamitous neurodegenerative disorder with no cure till date, is closely allied with the misfolding and aggregation of α-Synuclein (α -Syn). Inhibition of α-Syn aggregation is one of the optimistic approaches for the treatment for PD. Here, we carried out hypothesis-driven studies towards synthesising a series of pyrazolo-pyridine carboxylate containing compounds (7a–7m) targeted at reducing deleterious α-Syn aggregation. The target compounds were synthesized through multi-step organic synthesis reactions. From docking studies, compounds 7b, 7g and 7i displayed better interaction with the key residues of α-Syn with values: ?6.8, ?8.9 and ?7.2 Kcal/mol, respectively. In vivo transgenic C. elegans model of Synucleinopathy was used to evaluate the ability of the designed and synthesized compounds to inhibit α-Syn aggregation. These lead compounds 7b, 7g and 7i displayed 1.7, 2.4 and 1.5-fold inhibition of α-Syn with respect to the control. Further, the strategy of employing pyrazolo-pyridine-based compounds worked with success and these scaffolds could be further modified and validated for betterment of endpoints associated with PD.
Synthesis of new conjugates 1H-Pyrazolo[3,4-b]pyridine-phosphoramidate and evaluation against leishmania amazonensis
Medeiros, Antonia C. R. F.,Borges, Julio C.,Becker, Klaus M.,Rodrigues, Raquel F.,Leon, Leonor L.,Canto-Cavalheiro, Marilene,Bernardino, Alice M. R.,De Souza, Marcos C.,Pedrosa, Leandro F.
, p. 159 - 167 (2017/12/08)
In this research three series of substituted 1H-pyrazolo[3,4-b]pyridine phosphoramidates were synthesized and characterized by infrared,1H,13C, and31P nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. The products were obtained in good yields (67-83percent) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chloro-1H-pyrazolo[3,4-b]pyridines. These compounds were evaluated as antileishmanials against Leishmania amazonensis promastigotes in vitro. Among all, compounds of a series showed expressive antileishmanial activity. Two of them emerged as the most active, with IC50 values of 6.44 ± 1.49 and 12.25 ± 0.68 μM. The cytotoxicity of this series was assessed on murine cells and presented values similar to the reference drug pentamidine.
Design, synthesis and anti-P. falciparum activity of pyrazolopyridine–sulfonamide derivatives
Silva, Thais B.,Bernardino, Alice M.R.,Ferreira, Maria de Lourdes G.,Rogerio, Kamilla R.,Carvalho, Leonardo J.M.,Boechat, Nubia,Pinheiro, Luiz C.S.
, p. 4492 - 4498 (2016/08/23)
Ten 1-phenyl-1H-pyrazolo[3,4-b]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. These ten compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50values ranging from 3.46 to 9.30 μM. The most active derivatives with substituent R2= Cl or CH3at the benzenesulfonamide moiety exhibited the lowest IC50. Compounds with an R1= CO2Et substituent at the 5-position of the 1H-pyrazolo[3,4-b]pyridine ring presented lower activity than those with a CN substituent. The 1H-pyrazolo[3,4-b]pyridine system appears to be promising for further studies as an antimalarial for overcoming the burden of resistance in P. falciparum.
Mass spectrometry of heterocyclic compounds: Benzo[b]pyrazolo[3,4-b]-1,6-naphthyridines
Khakwani, Samia,Aslam, Samina,Shahi, Mehrzadi Noureen,Rolim Bernardino, Alice M.,Khan, Misbahul Ain
, p. 2385 - 2387 (2016/10/19)
The mass spectra of a number of benzo[b]pyrazolo[3,4-b]-1,6-naphthyridines are presented. The fragmentation involves elimination of CO molecule followed by other fragments, such as halogen (Cl, Br) or halogen acids (HCl, HBr) and HCN, etc.
Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors
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Page/Page column 22, (2010/01/31)
Compounds of the formula which are useful in disease conditions mediated by TNF-α, such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.
New tetracyclic heteroaromatic ring system 3H-benzo[b]pyrazolo[3, 4-h]-1, 6-naphthyridines
De Azevedo, Alexandre Reis,Frugulhetti, Izabel C.P.P.,Khan, Misbahul Ain,Khakwani, Samia,Bernardino, Alice M. Rolim
, p. 47 - 54 (2007/10/03)
Various derivatives of the tetracyclic ring system 3H-Benzo[b]pyrazolo[3,4-h]-1,6-naphthyridine were prepared from 4-anilino-1H-pyrazolo[3,4-b]pyridine-5-carboxylic acids by intramolecular cyclization employing phophoryl chloride. 1H NMR spectra of the various derivatives were recorder.
ACETYLENIC ORTHO-SULFONAMIDO AND PHOSPHINIC ACID AMIDO BICYCLIC HETEROARYL HYDROXAMIC ACIDS AS TACE INHIBITORS
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, (2008/06/13)
Compounds of the formula are provided wherein P and Q are provided that when P is Q is and vice versa; which are useful in disease conditions mediated by TNF- alpha , such as rheumatoid arthritis, osteoarthritis, sepsis, AIDS, ulcerative colitis, multiple sclerosis, Crohn's disease and degenerative cartilage loss.
Ortho-sulfonamido bicyclic hydroxamic acids as matrix metalloproteinase and TACE inhibitors
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, (2008/06/13)
This invention provides, low molecular weight, non-peptide inhibitors of matrix metalloproteinases and TNF-α converting enzyme (TACE, tumor necrosis factor-α converting enzyme) of formula: B wherein B is P and Q are provided that when P is Q is and vice versa; or a pharmaceutically acceptable salt thereof.
Preparation and use of ortho-sulfonamido bicyclic heteroaryl hydroxamic acids as matrix metalloproteinase and TACE inhibitors
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, (2008/06/13)
This invention provides, low molecular weight, non-peptide inhibitors of matrix metalloproteinases and TNF-α converting enzyme (TACE, tumor necrosis factor-α converting enzyme) of formula: B wherein B is T, U, W, and X are each, independently, carbon or nitrogen, provided that when T or U is carbon, either may be optionally substituted with R1; Y is carbon, nitrogen, oxygen or sulfur, provided that at least one of T, U, W, X, and Y is not carbon, and further provided that no more than 2 of T, U, W, and X are nitrogen; is a phenyl ring or is a heteroaryl ring of ring 5-6 atoms which may contain 0-2 heteratoms selected from nitrogen, oxygen, and sulfur, in addition to any heteroatoms defined by W or X; wherein the phenyl or heteroaryl ring may be optionally mono-, di-, or tri- substituted with R1; Z is a phenyl, naphthyl, heteroaryl, or heteroaryl fused to phenyl, wherein the heteroaryl moiety contains of 5-6 ring atoms and 1-3 heteroatoms selected from nitrogen, oxygen, or sulfur; wherein the phenyl, naphthyl, heteroaryl, or phenyl fused heteroaryl moieties may be optionally mono-, di-, or tri- substituted with R1; R1 is hydrogen, halogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cyclocalkyl of 3-6 carbon atoms, —(CH2)nZ, —OR2, —CN, —COR2, perfluoroalkyl of 1-4 carbon atoms, —CONR2R3, —S(O)xR2 —OPO(OR2)OR3, —PO(OR2)R3, —OC(O)NR2R3, —COOR2, —CONR2R3, —SO3H, —NR2R3, —NR2COR3, —NR2COOR3, —SO2NR2R3, —NO2, —N(R2)SO2R3, —NR2CONR2R3, —NR2C(═NR 3)NR2R3, —SO2NHCOR4, —CONHSO2R4, -tetrazol-5-yl, —SO2NHCN, —SO2NHCONR2R3 or Z; V is a saturated or partially unsaturated heterocycloalkyl ring of 5-7 ring atoms having 1-3 heteroatoms selected from N, O, or S, which may be optionally mono-, or di-substituted with R2; R2 and R3 are each, independently, hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R4 is alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R5 is hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, Z, or V; n=1-6; x=0-2 or a pharmaceutically acceptable salt thereof.
