In the title compound, C22H27NO3, the piperidine ring adopts a slightly distorted chair conformation. The dihedral angle between the two aromatic rings is 60.4 (1)°. In the crystal, the amino group forms a rather long N—H⋯O contact to a methoxy O atom. There are also C—H⋯O interactions present.
In the title compound, C20H21NO2, the piperidine ring adopts a distorted boat conformation. The phenyl rings substituted at the 2- and 6-positions of the piperidine ring subtend angles of 86.0 (1) and 67.3 (1)° with the mean plane of the piperidine ring (all six non-H atoms). The crystal packing features C—H⋯O interactions.
In the title compound, C11H9NO2, the quinoline ring system is essentially planar (r.m.s. deviation = 0.005 Å) and the methoxy and aldehyde groups are almost coplanar with it [N—C—O—C = 6.24 (19) and O—C—C—C = 0.3 (2)°]. In the crystal, molecules are linked by pairs of C—H⋯O hydrogen bonds, forming centrosymmetric R
2(10) dimers. The dimers are linked via π–π interactions involving the pyridine and benzene rings [centroid–centroid distance = 3.639 (1) Å].
In the title compound, C19H19NO2, commonly called koenimbine, the pyran ring adopts a sofa conformation. The carbazole ring system is planar [r.m.s. deviation = 0.063 (1) Å]. A C(10) zigzag chain running along the b axis is formed through intermolecular C—H⋯O hydrogen bonds. The chains are linked via weak C—H⋯π and N—H⋯π interactions.
In the title compound, C21H21Cl3N2O2, the piperidine ring adopts a distorted boat conformation. One of the chlorophenyl rings is almost perpendicular to the best plane through piperidine ring, making a dihedral angle of 88.7 (1)°, whereas the other ring is twisted by 71.8 (1)°. The crystal packing is stabilized by intermolecular C—H⋯O, C—H⋯Cl and O—H⋯O interactions.
In the title compound, C20H21NO2, the piperidine ring adopts a distorted boat conformation. The dihedral angle between the two phenyl rings is 61.33 (18)°. In the crystal, intermolecular C—H⋯O interactions link the molecules into zigzag C(5) chains running parallel to .
In the title compound, C22H24ClNO2, the piperidine ring adopts a distorted boat conformation. The dihedral angle between the two phenyl rings is 83.2 (1)°. In the crystal, the molecules are linked into chains running along the b axis by C—H⋯O hydrogen bonds. The Cl atom of the chloroacetyl group is disordered over two positions with occupancies of 0.66 (2) and 0.34 (2).
In the title compound, C23H27NO4, the piperidine ring adopts a distorted boat conformation. The methoxy groups lie in the plane of benzene rings to which they are attached [maximum deviations of 0.014 (3) and 0.007 (3) Å]. The benzene rings are oriented at angles of 67.2 (1) and 87.0 (1)° with respect to the best plane through the four co-planar atoms of the piperidine ring.
In the title compound, C22H23Cl2NO4, the piperidine ring adopts a distorted boat conformation. The methoxy groups lie in the plane of the benzene rings to which they are attached. The benzene rings are oriented at angles of 84.3 (1) and 76.8 (1)° with respect to the best plane through the piperidine ring. The crystal packing is stabilized by intermolecular C—H⋯O interactions.
In the title compound, C23H25Cl2NO4, the piperidine ring adopts a distorted boat conformation. The dihedral angle between the benzene rings is 54.8 (1)°. In the crystal, the molecules are linked into a two-dimensional network parallel to the ab plane by C—H⋯O hydrogen bonds.
There are two crystallographically independent molecules in the asymmetric unit of the title compound, C18H12Br2N2O. In each molecule, one of the bromophenyl rings lies almost in the plane of pyrazole unit [dihedral angles of 5.8 (3)° in the first molecule and and 5.1 (3)° in the second] while the other ring is approximately perpendicular to it [dihedral angles of 80.3 (3) and 76.5 (3)°]. The crystal packing shows intermolecular C—H⋯O interactions. The crystal studied was a racemic twin.
The title compound, C21H26N2O3, crystallizes with two independent molecules in the asymmetric unit. In both independent molecules, the diazepine ring adopts a chair conformation. In the crystal, the independent molecules exist as N—H⋯O hydrogen-bonded R
2(8) dimers which are linked via N—H⋯O hydrogen bonds, forming tetramers. The tetramers are linked by C—H⋯O hydrogen bonds. In one of the molecules in the asymmetric unit, the terminal C atom of the ethyl group is disordered over two positions with refined occupancies of 0.742 (4) and 0.258 (4).
In the title compound, [CoCl(C2H8N2)2(C7H9N)]Cl2·H2O, the CoIII ion has a distorted octahedral coordination environment and is surrounded by four N atoms in an equatorial plane, with the other N and Cl atoms occupying the axial positions. The crystal packing is stabilized by N—H⋯O, N—H⋯Cl and O—H⋯Cl interactions.
In the title compound, C19H22N2O, the diazepine ring adopts a distorted chair conformation. One of the N—H groups forms an intermolecular N—H⋯O hydrogen bond generating an R
2(8) graph-set motif. The other N—H group does not form a hydrogen bond.
There are two crystallographically independent molecules in the asymmetric unit of the title compound, C22H24ClNO4. The piperidine ring in both molecules adopts a distorted boat conformation. The crystal packing is stabilized by C—H⋯O and C—H⋯Cl interactions.
There are two crystallographically independent organic molecules in the asymmetric unit of the title compound, C12H12Cl2N2O2·0.5H2O. The benzodiazepine ring adopts a distorted boat conformation in both molecules. The crystal packing is controlled by N—H⋯O, C—H⋯O and O—H⋯O intra- and intermolecular hydrogen bonds. A graph-set motif of R
3(14) dimer formation by a combination of N—H⋯O, O—H⋯O and C—H⋯O hydrogen bonds stabilizes the molecules and extends along a axis.
In the title compound, C11H12N2O2, a benzodiazepine derivative, the seven-membered ring adopts a distorted boat conformation. The crystal packing is controlled by intermolecular N—H⋯O and C—H⋯O interactions.
In the title compound, [CoCl(C2H8N2)2(C7H9N)]Cl2·0.5H2O, there are two crystallographically independent cations and anions and one water molecule in the asymmetric unit. Both CoIII ions are bonded to two chelating ethylenediamine ligands, one benzylamine molecule and one chloride ion. The crystal packing is through N—H⋯O, N—H⋯Cl and O—H⋯Cl interactions.
In the title compound, C19H24N2O2S, the benzodiazepine ring adopts a distorted boat conformation. The S atom shows a distorted tetrahedral geometry, with the O—S—O [119.16 (14)°] and N—S—C [107.48 (10)°] angles deviating significantly from ideal values. The crystal packing is controlled by C—H⋯O, N—H⋯O and C—H⋯π interactions.
In the title compound, C12H13ClN2O2, the benzodiazepine ring adopts a distorted boat conformation. The carbonyl O atom and the Cl atom of the chloroacetyl group are in a cis conformation. The crystal packing is controlled by intermolecular C—H⋯O and N—H⋯O interactions.
The adapter protein Shc is a critical component of mitogenic signaling pathways initiated by a number of receptors. Shc can directly bind to several tyrosine-phosphorylated receptors through its phosphotyrosine-binding (PTB) domain, and a role for the PTB domain in phosphotyrosine-mediated signaling has been well documented. The structure of the Shc PTB domain demonstrated a striking homology to the structures of pleckstrin homology domains, which suggested acidic phospholipids as a second ligand for the Shc PTB domain. Here we demonstrate that Shc binding via its PTB domain to acidic phospholipids is as critical as binding to phosphotyrosine for leading to Shc phosphorylation. Through structure-based, targeted mutagenesis of the Shc PTB domain, we first identified the residues within the PTB domain critical for phospholipid binding in vitro. In vivo, the PTB domain was essential for localization of Shc to the membrane, as mutant Shc proteins that failed to interact with phospholipids in vitro also failed to localize to the membrane. We also observed that PTB domain-dependent targeting to the membrane preceded the PTB domain's interaction with the tyrosine-phosphorylated receptor and that both events were essential for tyrosine phosphorylation of Shc following receptor activation. Thus, Shc, through its interaction with two different ligands, is able to accomplish both membrane localization and binding to the activated receptor via a single PTB domain.
The adapter protein Shc has been implicated in Ras signaling via many receptors, including the T-cell antigen receptor (TCR), B-cell antigen receptor, interleukin-2 receptor, interleukin-3 receptor, erythropoietin receptor, and insulin receptor. Moreover, transformation via polyomavirus middle T antigen is dependent on its interaction with Shc and Shc tyrosine phosphorylation. One of the mechanisms of TCR-mediated, tyrosine kinase-dependent Ras activation involves the simultaneous interaction of phosphorylated Shc with the TCR zeta chain and with a second adapter protein, Grb2. Grb2, in turn, interacts with the Ras guanine nucleotide exchange factor mSOS, thereby leading to Ras activation. Although it has been reported that in fibroblasts Grb2 and mSOS constitutively associate with each other and that growth factor stimulation does not alter the levels of Grb2:mSOS association, we show here that TCR stimulation leads to a significant increase in the levels of Grb2 associated with mSOS. This enhanced Grb2:mSOS association, which occurs through an SH3-proline-rich sequence interaction, is regulated through the SH2 domain of Grb2. The following observations support a role for Shc in regulating the Grb2:mSOS association: (i) a phosphopeptide corresponding to the sequence surrounding Tyr-317 of Shc, which displaces Shc from Grb2, abolished the enhanced association between Grb2 and mSOS; and (ii) addition of phosphorylated Shc to unactivated T cell lysates was sufficient to enhance the interaction of Grb2 with mSOS. Furthermore, using fusion proteins encoding different domains of Shc, we show that the collagen homology domain of Shc (which includes the Tyr-317 site) can mediate this effect. Thus, the Shc-mediated regulation of Grb2:mSOS association may provide a means for controlling the extent of Ras activation following receptor stimulation.
The phosphorylation and dephosphorylation of proteins on tyrosyl residues are key regulatory mechanisms in T-cell signal transduction and are controlled by the opposing activities of protein tyrosine kinases and phosphotyrosyl phosphatases (PTPs). In T cells, several nontransmembrane protein tyrosine kinases are associated with receptors; for example, Lck is bound to the coreceptors CD4 and CD8 and becomes activated upon their stimulation. In comparison, little is known about the role of nontransmembrane PTPs in early T-cell signaling. SH-PTP1 (PTP1C, HCP, SHP) is a nontransmembrane PTP expressed primarily in hematopoietic cells, including T cells. We have found that SH-PTP1 is basally phosphorylated on serine in resting T cells. Upon stimulation of CD4 or CD8 either in a T-cell hybridoma cell line or in primary thymocytes, SH-PTP1 becomes tyrosyl phosphorylated. Moreover, SH-PTP1 is constitutively phosphorylated on tyrosine in the Lck-overexpressing lymphoma cell line LSTRA. SH-PTP1 is also a good substrate for recombinant Lck in vitro. Comparisons of the tryptic phosphopeptide maps of wild-type SH-PTP1 and deletion and point mutations establish that the two sites (Y-536 and Y-564) which are directly phosphorylated by Lck in vitro are also phosphorylated in vivo in LSTRA cells. One of these sites (Y-564) is phosphorylated in T cells in response to Lck activation. We conclude that SH-PTP1 undergoes Lck-dependent tyrosyl phosphorylation in T cells and likely plays a role in early T-cell signaling.