Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors.

ABSTRACT: From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure.

SUBMITTER: Halland N

PROVIDER: S-EPMC4291729 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Discovery of N-[4-(1H-Pyrazolo[3,4-b]pyrazin-6-yl)-phenyl]-sulfonamides as Highly Active and Selective SGK1 Inhibitors.

Halland Nis N Schmidt Friedemann F Weiss Tilo T Saas Joachim J Li Ziyu Z Czech Jörg J Dreyer Matthias M Hofmeister Armin A Mertsch Katharina K Dietz Uwe U Strübing Carsten C Nazare Marc M

ACS medicinal chemistry letters 20141023 1

From a virtual screening starting point, inhibitors of the serum and glucocorticoid regulated kinase 1 were developed through a combination of classical medicinal chemistry and library approaches. This resulted in highly active small molecules with nanomolar activity and a good overall in vitro and ADME profile. Furthermore, the compounds exhibited unusually high kinase and off-target selectivity due to their rigid structure. ...[more]

PMID: 25589934

Similar Datasets

Crystal structure of 5-(4,5-di-hydro-1H-imidazol-2-yl)-3-methyl-1-phenyl-1H-pyrazolo-[3,4-b]pyrazin-6-amine.

Project description:In the title compound, C15H15N7, the phenyl ring is inclined by 19.86?(5)° to the mean plane of the pyrazolo-[3,4-b]pyrazine core. In the crystal, N-H?N and C-H?N hydrogen bonds form [010] chains, which stack via ?-? inter-actions [centroid-centroid distance between the pyrazole rings = 3.4322?(7)?Å].

| S-EPMC4257272 | biostudies-literature

3,4,6-Trimethyl-1-phenyl-1H-pyrazolo-[3,4-b]pyridine.

Project description:In the title compound, C(15)H(15)N(3), the 1H-pyrazolo-[3,4-b]pyridine system and the phenyl ring are each individually planar, with r.m.s. deviations of 0.017?(2) and 0.011?(2)?Å, respectively; the dihedral angle between the two aromatic systems is 9.33?(10)°. The crystal packing is stabilized by offset ?-? stacking between parallel pyrazolo-[3,4-b]pyridine ring systems [face-to-face distance = 3.449?(6)?Å].

| S-EPMC3007300 | biostudies-literature

Crystal structure of (2-hy-droxy-5-methyl-phen-yl)(3-methyl-1-phenyl-1H-pyrazolo-[3,4-b]pyridin-5-yl)methanone.

Project description:In the title compound, C21H17N3O2, the 2-hy-droxy-5-methyl-phenyl ring and the phenyl ring are inclined to the mean plane of the pyrazolo-pyridine moiety (r.m.s. deviation = 0.013 Å) by 52.89 (9) and 19.63 (8)°, respectively, and to each other by 42.83 (11)°. In the mol-ecule, there are intra-molecular O-H⋯O and C-H⋯N hydrogen bonds, both enclosing an S(6) ring motif. In the crystal, mol-ecules stack along the c-axis direction, forming columns within which there are a number of π-π inter-actions [the inter-centroid distances vary from 3.5278 (10) to 3.8625 (10) Å]. The columns are linked by C-H⋯π inter-actions, forming slabs parallel to (100).

| S-EPMC4518926 | biostudies-literature

2-(4-Chloro-phen-yl)-5-(3,4-dimethoxy-pheneth-yl)-6,7-dihydro-pyrazolo[1,5-a]pyrazin-4(5H)-one.

Project description:In the title compound, C(22)H(22)ClN(3)O(3), the dihedral angles between the planes of the benzene rings and the pyrazole ring are 16.05?(10) and 84.84?(10)°. The conformation of the six-membered heterocyclic ring is close to a screw-boat. The crystal packing is stabilized by weak inter-molecular C-H?O inter-actions and is also consolidated by C-H?? inter-actions.

| S-EPMC2969350 | biostudies-literature

Organometallic 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines as potential anticancer agents.

Project description:Six organometallic complexes of the general formula [M(II)Cl(?(6)-p-cymene)(L)]Cl, where M = Ru (11a, 12a, 13a) or Os (11b, 12b, 13b) and L = 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1-L3) have been synthesized. The latter are known as potential cyclin-dependent kinase (Cdk) inhibitors. All compounds have been comprehensively characterized by elemental analysis, one- and two-dimensional NMR spectroscopy, UV-vis spectroscopy, ESI mass spectrometry, and X-ray crystallography (11b and 12b). The multistep synthesis of 3-(1H-benzimidazol-2-yl)-1H-pyrazolo[3,4-b]pyridines (L1-L3), which was reported by other researchers, has been modified by us essentially (e.g., the synthesis of 5-bromo-1H-pyrazolo[3,4-b]pyridine-3-carboxylic acid (3) via 5-bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine (2); the synthesis of 1-methoxymethyl-2,3-diaminobenzene (5) by avoiding the use of unstable 2,3-diaminobenzyl alcohol; and the activation of 1H-pyrazolo[3,4-b]pyridine-3-carboxylic acids (1, 3) through the use of an inexpensive coupling reagent, N,N'-carbonyldiimidazole (CDI)). Stabilization of the 7b tautomer of methoxymethyl-substituted L3 by coordination to a metal(II) center, as well as the NMR spectroscopic characterization of two tautomers 7b-L3 and 4b'-L3 in a metal-free state are described. Structure-activity relationships with regard to cytotoxicity and cell cycle effects in human cancer cells, as well as Cdk inhibitory activity, are also reported.

| S-EPMC3255473 | biostudies-literature

6,7-Dihydro-4-(4-methoxy-phen-yl)-3-methyl-6-oxo-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbonitrile.

Project description:In the title compound, C(21)H(16)N(4)O(2), the dihedral angle between the meth-oxy-substituted benzene ring and the ring system formed by the pyridinone ring and the pyrazole ring is 57.4?(1)°, and that between the unsubstituted phenyl ring and the ring system is 135.6?(1)°. In the crystal structure, mol-ecules are linked together via inter-molecular N-H?O hydrogen bonds.

| S-EPMC2959259 | biostudies-literature

3,6-Dimethyl-1-phenyl-4-(2-thien-yl)-8-(2-thienylmethyl-ene)-5,6,7,8-tetra-hydro-1H-pyrazolo[3,4-b][1,6]naphthyridine.

Project description:In the mol-ecule of the title compound, C(26)H(22)N(4)S(2), the pyrazole ring is oriented at a dihedral angle of 0.85 (3)° with respect to the adjacent naphthyridine ring, while the other ring of naphthyridine adopts an envelope conformation. The dihedral angle between phenyl and pyrazole rings is 87.65 (3)°. In the crystal structure, weak inter-molecular C-H⋯N inter-actions link the mol-ecules into chains. The π-π contacts between the naphthyridine rings and the naphthyridine and thio-phene rings [centroid-centroid distances = 3.766 (3) and 3.878 (3) Å] may further stabilize the structure. A weak C-H⋯π inter-action is also present.

| S-EPMC2977787 | biostudies-literature

4-(4-Bromo-phen-yl)-3-methyl-1-phenyl-6,7-dihydro-1H-pyrazolo-[3,4-b]thieno[2,3-e]pyridine 5,5-dioxide.

Project description:In the title compound, C(21)H(16)BrN(3)O(2)S, the pyrazole and pyridine rings are nearly coplanar, the dihedral angle between their planes being 3.17 (14)°. The 2,3-dihydro-thio-phene ring adopts an envelope conformation. The 4-bromo-phen-yl/pyridine ring and phen-yl/pyrazole rings form dihedral angles of 60.06 (9) and 33.49 (11)°, respectively. There is an intra-molecular C-H⋯N hydrogen bond. The crystal packing is stabilized by inter-molecular C-H⋯O hydrogen bonding and C-H⋯π inter-actions.

| S-EPMC3238837 | biostudies-literature

5-(Pyridin-4-ylmeth-yl)-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one.

Project description:In the title compound, C(11)H(9)N(5)O, the pyrazolo-pyrimidin-4-one ring system is almost planar, with a maximum deviation of 0.0546?(13)?Å for the O atom. The crystal packing is stabilized by inter-molecular N-H?N, C-H?O and C-H?N hydrogen bonds. In addition, ?-? stacking is found between the pyridine ring and the pyrazolo-pyrimidin-4-one ring systems, with centroid-centroid distances in the range 3.9627?(12)-4.6781?(12)?Å.

| S-EPMC3212314 | biostudies-literature

1-(2-Chloro-eth-yl)-1H-pyrazolo-[3,4-d]pyrimidin-4(5H)-one.

Project description:In the title compound, C(7)H(7)ClN(4)O, the pyrazolo-pyrimidine ring is essentially planar, the r.m.s. deviation of the fitted atoms being 0.0071 Å. The crystal structure features strong N-H⋯O hydrogen bonds and further consolidated by weak C-H⋯O, C-H⋯N and C-H⋯Cl inter-actions.

| S-EPMC3393899 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data