Resolution and chiral recognition of muscone as well as actions on neural system.

In this letter, (R)-muscone and (S)-muscone were prepared by optical resolution of dl-muscone using N,N'-dibenzyl-l-tartaramide or N,N'-dibenzyl-d-tartaramide, according to the method reported by Kunihiko Takabe. But we separated the diastereomers using EtOH instead of MeOH in the recrystallization step to get the goal product with higher optical purity and yield. The regulatory effect of muscone and its enantiomer on the neural system showed that they could prolong mouse hypoxia tolerance and dose-dependently enhance mouse spinal cord stimulation induced by strychnine nitrate.

[Design, synthesis and biological evaluation of fingolimod analogues containing diphenyl ether moiety].

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity.

[Effect of a novel selective S1P1 agonist, Syl948, on mouse skin transplantation].

Syl948 is a synthesized selective S1P1 agonist with novel structure. HTRF-IP1 test indicated that Syl948-P, the active form of Syl948 in vitro, has strong activity against S1P1 (EC50: 83 +/- 16 nmol x L(-1)), but its effect on S1P3 was very weak (EC50: 1 026 +/- 90 nmol x L(-1)). In SD rats, oral administration of Syl948 10 mg x kg(-1) significantly decreased the peripheral blood lymphocytes (PBL), with the maximal PBL inhibition rate of 63%, which was as similar as equal dose of fingolimod (FTY720).

Synthesis and in vitro antitumor activities of novel benzyl urea analogues of sorafenib.

A novel series of benzyl urea analogues based on the structural modification of sorafenib were synthesized. Their in vitro antitumor activities against MX-1, HepG2, Ketr3 and HT-29 were evaluated using the standard MTT assay. While several target compounds showed inhibitory activity against multiple cancer cell lines, compound 9 was of particular interest, demonstrating IC50 values (5.

Synthesis and anti-tubercular activity of novel alkyl substituted riminophenazine derivatives.

A series of novel riminophenazine derivatives bearing an alkyl substituent attached to N-5 and imino nitrogen at C-3 position of the phenazine ring were obtained through rational drug design, aiming to maintain high anti-tubercular activity, lower toxicity and reduce lipophilicity. All target compounds were prepared by utilizing simple and flexible synthetic route and evaluated against Mycobacterium tuberculosis H37Rv and screened for mammalian cytotoxicity. The results demonstrated that compounds with a cyclopropyl substituent at N-5 position were more active than the reference compound clofazimine.

[Design, synthesis and in vitro activity of glycinamide-bearing compounds as DPP-IV inhibitors].

To research the structure-activity relationship (SAR) of glycinamide-bearing compounds that used as inhibitors of dipeptidyl peptidase IV (DPP-IV), P32/98 and compound A were chosen as the leading compounds, heterocycles containing nitrogen atom were introduced to form amide, and different residues on a-position of carbonyl were designed. The nineteen designed compounds were synthesized by a simple route and were evaluated as inhibitors of DPP-IV. All of the structures were characterized by 1H NMR and HRMS.

Four new minor taxanes from cell cultures of Taxus chinensis.

Four new minor taxanes (1-4) have been isolated from Ts-19 cell cultures of Taxus chinensis together with five known taxanes (5-9) by silica gel chromatography combined with semi-preparative HPLC chromatography. On the basis of the analyses of the chemical and spectroscopic (IR, MS, 1D, and 2D NMR) data, the structures of new compounds were elucidated as 5alpha-hydroxy-2alpha,10beta-diacetoxy-14beta-(3-hydroxy-2-methyl-butyryl)oxytaxa-4(20),11-diene (1), 2alpha,5alpha,10beta-triacetoxy-14beta-(2-hydroxy-propionyl)oxytaxa-4(20),11-diene (2), 2alpha,5alpha,10beta-triacetoxy-14beta-(2-hydroxy-3-methyl-butyryl)oxytaxa-4(20),11-diene (3), and 2alpha-benzoxy-4alpha,9alpha,10beta,13alpha-tetraacetoxytax-11-ene (4), respectively. Compounds 1-5 were pharmacologically evaluated for their cytotoxicities against five human cancer cell lines (HCT-8, Bel-7402, BGC-823, A549, and A2780) and their reversing activity towards multi-drug resistance A549/taxol tumor cell line, and the results showed that all of the tested compounds exhibited very low cytotoxicities, while compound 4 possessed twice the reversing activity as that of verapamil at 10 muM.

Overcoming tumor drug resistance with high-affinity taxanes: a SAR study of C2-modified 7-acyl-10-deacetyl cephalomannines.

A series of C2-modified 10-deacetyl-7-propionyl cephalomannine derivatives was designed, prepared, and biologically evaluated. Some C2 meta-substituted benzoate analogues showed potent activity against both drug-sensitive and drug-resistant tumor cells in which resistance is mediated through either P-gp overexpression or beta-tubulin mutation mechanisms. The taxoid 15 b and related compounds are of particular interest, as they are much more cytotoxic than paclitaxel, especially against drug-resistant tumor cells; they are able to kill both drug-resistant and drug-sensitive cells (low R/S ratio), and they have high affinity for beta-tubulin.

Cytotoxic effect of a non-peptidic small molecular inhibitor of the p53-HDM2 interaction on tumor cells.

Aim: To investigate if non-peptidic small molecular inhibitors of the p53-HDM2 interaction could restore p53 function and kill tumor cells.

Methods: A series of non-peptidic small HDM2 inhibitors were designed by computer-aided model and synthesized by chemical method. Syl-155 was one of these inhibitors.

[MESH diagrams of Chinese in Beijing and its preliminary application in practice].

Objective: To establish the normal MESH diagrams of Chinese in Beijing, and to build a computerized MESH analysis system for orthodontic practice.

Methods: Twenty-eight subjects with normal occlusion were selected in Beijing and their lateral cephalograms were taken at the age of thirteen and eighteen, respectively. Individual MESH diagrams were then established for each subject mainly according to Moorrees' method from the cephalograms orientated in estimated natural head position.

[Surgical treatment of fibrous dysplasia of the skull with neuro-navagation].

Objective: To evaluate the role and effect of neuro-navagation in the surgical treatment of fibrous dysplasia of the skull and to discuss the indication and advantages of transcranial optic nerve decompression are discussed.

Methods: Fifteen patients with fibrous dysplasia of skull, 6 males and 9 females, aged 10.3 (5 approximately 21), were surgically treated by transcranial approach.

[Transcranial optic nerve decompression for optic nerve injury].

Objective: To discuss the operative indications and advantages of transcranial optic nerve decompression in treatment of optic nerve injury resulted from skull base fracture.

Methods: The data, such as the site of impact, vision, ocular movement, characteristic of CT, and pathologic changes during operation, and the extent of operative decompression of 118 patients with optic nerve injury. According the site of impact on the head, 87 of lateral superciliary arch type, 18 of medial superciliary arch type, and 13 of zygomatic type, undergoing transcranial optic nerve decompression were analyzed retrospectively.

[Synthesis and drug resistant reversal activities of taxane-like multi-drug resistant reversal agents].

Aim: To design and synthesize a series of new taxoids with a 5-O-sidechain, and to test the multi-drug resistant reversal activity of these compound on KB/V200 cells which is 180 times more resistant to vincristine.

Methods: Using Sinenxan A as a common synthetic starting material, three different types of 5-O-sidechain molecules were synthesized through different route. For type I compounds, 14-acetoxy of Sinenxan A was selectively removed by hydrolysis, xanthation and reduction with tributyltin; A C-10-oxo group was introduced by PCC oxidation; 5-O-acetyl group was selectively removed by potassium tert-butoxide and finally the side chain was introduced by acylating with the corresponding acid.