ABSTRACT
Diels-Alder reaction between furan and maleic anhydride resulted in 5,6-dehydro norcantharidin, then norcantharidin was obtained by reduction. The substituted-carboxylic acid was condensed with N-aminothiourea in presence of phosphorus oxychloride, yielding 2-amino-1,3,4-thiadiazole derivatives. Novel norcantharidin derivatives were synthesized with acylation, then intramolecular condensation using norcantharidin (or 5,6-dehydro norcantharidin) and 2-amino- 1,3,4-thiadiazole derivatives. All the target compounds were confirmed by IR, (1)HNMR, ESI-MS and were reported for the first time. Norcantharidin derivatives antiproliferative assay was tested by MTT method against A549 and PC-3 cell lines. The results showed that all the norcantharidin derivatives displayed moderate inhibitory activities.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Bridged Bicyclo Compounds, Heterocyclic/pharmacology , Antineoplastic Agents/chemistry , Bridged Bicyclo Compounds, Heterocyclic/chemical synthesis , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Molecular Conformation , Molecular Structure , Structure-Activity RelationshipABSTRACT
In the title compound, C(14)H(16)ClN(3)O(2)S, the dihedral angle between the 4-chloro-phenyl and 1,3,4-oxadiazole rings is 67.1â (1)° and the orientation of the amide N-H and C=O bonds is anti. In the crystal, mol-ecules are linked by N-Hâ¯O and N-Hâ¯S hydrogen bonds.
ABSTRACT
In the structure of the title compound, C(18)H(15)ClN(4)O(4)S, the dihedral angle between the two benzene rings is 1.4â (3)°. The angle between the phenyl ring and thia-diazole ring is 5.8â (4)°. The conformations of the N-H and C=O bonds are anti with respect to each other. In the crystal structure, mol-ecules are linked by inter-molecular O-Hâ¯N, N-Hâ¯O and O-Hâ¯O hydrogen bonds, forming a three-dimensional network.
ABSTRACT
Aminopeptidase N (APN) is a zinc-dependent ectopeptidase which plays an important role in the invasion of metastatic tumors. In this study, we report the synthesis and in vitro enzyme inhibition assay of 1,3,4-thiadiazole scaffold compounds. These new compounds have potent inhibitory activities toward APN with IC50 values in the micromolar range.
Subject(s)
CD13 Antigens/antagonists & inhibitors , Protease Inhibitors/chemical synthesis , Protease Inhibitors/pharmacology , Thiadiazoles/chemical synthesis , Thiadiazoles/pharmacology , Indicators and Reagents , Leucine/analogs & derivatives , Leucine/chemistry , Leucine/pharmacology , Matrix Metalloproteinase Inhibitors , Structure-Activity RelationshipABSTRACT
The asymmetric unit of the crystal structure of the title compound, C(8)H(9)ClN(2)O(2), contains four independent mol-ecules. The dihedral angles between the urea N-(C=O)-N planes and the benzene rings are 83.3â (3), 87.8â (1), 89.1â (1) and 17.5â (2)° in the four mol-ecules. Extensive N-Hâ¯O hydrogen bonding is present in the crystal structure.
ABSTRACT
In the structure of the title compound, C(17)H(13)BrN(4)O(2)S, the dihedral angle between the two benzene rings is 38.5â (1)°; the angle between the 4-bromo-benzene and thia-diazole rings is 1.3â (1)°. The conformations of the N-H and C=O bonds are anti with respect to each other. The structure displays inter-molecular N-Hâ¯O and C-Hâ¯O hydrogen bonding, with both interactions leading to inversion dimers.
ABSTRACT
Both the aminopeptidase N (APN) and matrix metalloproteinase (MMP) are essential metallopeptidases in the development of tumor invasion and angiogenesis. A series of novel peptide-like derivatives were designed and synthesized as antitumor agents. Their structures were confirmed by IR, MS, and (1)H-NMR. These compounds exhibited potent inhibitory activities against APN and low activity against MMP in vitro. The derivatives with methoxy group show better activities than those with other substituted group and could be used as lead compounds for exploring new APN inhibitors in the future.
Subject(s)
CD13 Antigens/antagonists & inhibitors , Peptides/chemical synthesis , Peptides/pharmacology , Protease Inhibitors/chemical synthesis , Protease Inhibitors/pharmacology , Escherichia coli/chemistry , Hydrogen Bonding , Mass Spectrometry , Matrix Metalloproteinase Inhibitors , Spectrometry, Mass, Electrospray Ionization , Spectrophotometry, InfraredABSTRACT
The asymmetric unit of the title compound, C(21)H(20)N(4)O(3)S, contains two independent mol-ecules. The dihedral angles between the two benzene rings are 47.6â (1) and 30.2â (1)°, the corresponding values between the p-methoxy-benzene and thia-diazol rings are 12.3â (1) and 24.7â (1)°, respectively, for the two mol-ecules. The conformations of the N-H and C=O bonds are anti with respect to each other. The enone groups show a trans configuration. The crystal structure is stabilized by N-Hâ¯O and N-Hâ¯N inter-actions. The absolute structure could not be determined from the X-ray data but the absolute configuration has been assigned by reference to an unchanging chiral centre in the synthetic procedure.
ABSTRACT
In the title compound, C(20)H(17)ClN(4)O(2)S, the dihedral angle between the two benzene rings is 65.9â (1)°; the corresponding angle between the 4-chloro-phenyl and thia-diazole rings is 3.4â (8)°. The conformations of the N-H and C=O bonds are anti with respect to each other. The enone groups show a trans configuration. The structure displays intermolecular N-Hâ¯O, C-Hâ¯N, C-Hâ¯S and C-Hâ¯O hydrogen bonding.
