Chengdu DiAo Pharmaceutical Group Co.

Chengdu, China

Chengdu DiAo Pharmaceutical Group Co.

Chengdu, China
SEARCH FILTERS
Time filter
Source Type

Chen X.,Zhejiang University | Yang W.,Zhejiang University | Fan Y.,Zhejiang University | Luo J.,Thomas Jefferson University | And 6 more authors.
British Journal of Pharmacology | Year: 2010

BACKGROUND AND PURPOSE The cannabinoid CB 1 receptor is primarily thought to be functionally coupled to the G i form of G proteins, through which it negatively regulates cAMP accumulation. Here, we investigated the dual coupling properties of CB 1 receptors and characterized the structural determinants that mediate selective coupling to G s and G i.EXPERIMENTAL APPROACH A cAMP-response element reporter gene system was employed to quantitatively analyze cAMP change. CB 1/CB 2 receptor chimeras and site-directed mutagenesis combined with functional assays and computer modelling were used to determine the structural determinants mediating selective coupling to G s and G i.KEY RESULTS CB 1 receptors could couple to both G s-mediated cAMP accumulation and G i-induced activation of ERK1/2 and Ca 2+ mobilization, whereas CB 2 receptors selectively coupled to G i and inhibited cAMP production. Using CB 1/CB 2 chimeric receptors, the second intracellular loop (ICL2) of the CB 1 receptor was identified as primarily responsible for mediating G s and G i coupling specificity. Furthermore, mutation of Leu-222 in ICL2 to either Ala or Pro switched G protein coupling from G s to G i, while to Ile or Val led to balanced coupling of the mutant receptor with G s and G i.CONCLUSIONS AND IMPLICATIONS The ICL2 of CB 1 receptors and in particular Leu-222, which resides within a highly conserved DRY(X) 5PL motif, played a critical role in G s and G i protein coupling and specificity. Our studies provide new insight into the mechanisms governing the coupling of CB 1 receptors to G proteins and cannabinoid-induced tolerance. © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.


Dong G.-X.,Chengdu Diao Pharmaceutical Group Co | Li W.-W.,Chengdu Diao Pharmaceutical Group Co | Wang R.-Z.,Chengdu Diao Pharmaceutical Group Co | Zou W.-J.,Chengdu University of Traditional Chinese Medicine | And 2 more authors.
Journal of Cardiovascular Pharmacology | Year: 2017

Di'ao Xinxuekang (XXK) is an herbal product in China and the Netherlands that has been clinically shown to attenuate atherosclerosis; however, the underlying antiatherosclerotic mechanism remains unclear. Because of its role in cholesterol homeostasis, reverse cholesterol transport (RCT) is a potential target for these beneficial effects. This study investigated the effects of XXK on RCT and related proteins. After treating ApoE-deficient mice with XXK for 8 weeks, we observed an increase in the expression level of ATP-binding cassette transporter A1 and ATP-binding cassette transporter G1, which in turn stimulated cholesterol efflux and reduced aortic atherosclerotic lesion area. XXK also increased high-density lipoprotein (HDL) synthesis by modulating the peroxisome proliferator-activated receptor γ/liver X receptor α/ATP-binding cassette transporter A1 pathway and promoted HDL maturity by increasing serum lecithin-cholesterol acyltransferase. In addition, XXK improved the selective uptake of HDL-cholesteryl ester by increasing the expression of scavenger receptor class B type I. This is the first study to show that XXK confers a regulation of RCT, at least in part, by improving HDL synthesis, maturation, and catabolism. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.


Wang H.,Southwest University | Yan J.-F.,Chengdu DiAo Pharmaceutical Group Co. | Song X.-L.,Southwest University | Fan L.,Southwest University | And 4 more authors.
Bioorganic and Medicinal Chemistry | Year: 2012

We wish to report the further design and improved synthesis that resulted in two series of target molecules, TM-1 and TM-2, with remarkably simplified structures containing β-amino ketone of discrete nabumetone moiety. These were obtained via a 'one-pot, two-step, three-component' protocol of Mannich reaction with yield up to 97%. A total of 28 out of 31 new compounds were characterized using 1H NMR, 13C NMR, ESI MS and HRMS techniques. Studies on their antidiabetic activities, screened in vitro at 10 μg mL -1 level, indicate that TM-2 possesses peroxisome proliferator-activated receptor activation and α-glucosidase inhibition activity significantly stronger than that of TM-1, and also that of the series B compounds that were previously synthesized by the group. Analysis of the structure-activity relationship points to the sulfanilamide unit as the most probable potent group of β-amino ketone and, on the basis of which, a tangible strategy is presented for the development of new antidiabetic drugs. © 2011 Elsevier Ltd. All rights reserved.


Yang Y.,Southwest University | Yan J.-F.,Chengdu DiAo Pharmaceutical Group Co. | Fan L.,Southwest University | Chen X.,Chengdu DiAo Pharmaceutical Group Co. | And 2 more authors.
Yaoxue Xuebao | Year: 2012

The discovery of high performance leading antidiabetic compounds containing sulfonamide and 4-aminophenylacetic acid moieties is reported. This was achieved by the synthesis of 6 intermediates and subsequently 20 target molecules using 4-aminophenylacetic acid as the starting materials, and through a few synthetic routes aided by multi-step reactions including sulfonylation of amino group, deacylation of amides and esterification of carboxyl group, as well as acylation of amino group. The chemical structures of the twenty-four new compounds were determined using 1H NMR, 13C NMR and HR-MS techniques. Screening in vitro of their peroxisome proliferator-activated receptor (PPAR) activation activities showed weak relative PPAR activation activities to most of the target molecules. However, 4 target molecules exhibit PPAR over 58%, and as high as 81.79% for TM2-i, presenting itself as potent leading compound for antidiabetic drugs. This research also confirms that it is probable to achieve esterification of carboxyl group and deacylation of fatty acid N-phenyl amides concurrently in SOCl2/alcohol solvent system. This provides new synthetic method for the selective reaction within molecules containing both carboxyl and N-aryl amido groups of fatty acids.


Tang G.,Southwest University | Yan J.,Chengdu di Ao Pharmaceutical Group Co. | Fan L.,Southwest University | Xu J.,Southwest University | And 4 more authors.
Science China Chemistry | Year: 2013

The synthesis of two series of β-amino ketones containing a p-aminobenzoic acid moiety (TM-1 and TM-2) using a modified protocol of the Mannich reaction is reported. The molecular structures of a total of tweenty three new target compounds were characterized by 1H NMR, 13C NMR, ESI-MS and HR-MS. Subsequently, their antidiabetic activities were screened in vitro. The α-glucodase inhibition (α-GI) activity of compound 1e reached a remarkable level of 66.50%. The peroxisome proliferator-activated receptor (PPAR) relative activation activities of six compounds are above 80%, and in particular 2i displays an unprecedentedly high PPAR of 130.91%. The structure-activity relationships of the compounds were established. 2i is also subject to further in-depth investigation. © 2013 Science China Press and Springer-Verlag Berlin Heidelberg.


Zhang K.,Southwest University | Yan J.-F.,Chengdu di Ao Pharmaceutical Group Co. | Tang X.-M.,Southwest University | Liu H.-P.,Southwest University | And 3 more authors.
Yaoxue Xuebao | Year: 2011

Twenty five new β-aminoalcohols containing nabumetone moiety were prepared via the reduction of potassium borohydride with a convenient and efficient procedure, starting from β-aminoketones that have been synthesized by our group. Their chemical structures were determined by IR, MS, 1H NMR, 13C NMR, HR-MS and antidiabetic activities were screened in vitro. Preliminary results revealed that the antidiabetic activity of most β-aminoalcohols were better than that of the corresponding β-aminoketones. Although most compounds showed weak antidiabetic activity, the α-glucosidase inhibitory activity of compounds 5hd1 and 5id2 reached 74.37% and 90.15%, respectively, which were superior to the positive control. The relative peroxisome proliferator-activated receptor response element (PPRE) activity of five compounds were more than 60%, among them compound 5ca possessed the highest activity (112.59%). As lead molecules of antidiabetic agents, compounds 5hd1, 5id2 and 5ca deserve further study.


Trademark
Chengdu Diao Pharmaceutical Group Co. | Date: 2011-02-14

Medicines for the treatment of cardiovascular diseases; Medicinal drinks; Food for babies; Air purifying preparations; Dietetic foods, namely, crackers adapted for medical use; Pesticides; Cotton for medical purposes; Dental lacquer.


Patent
Chengdu Diao Pharmaceutical Group Co. | Date: 2015-08-13

Disclosed are a phthalic hydrazide (phthalazine ketone) compound, and a pharmaceutical composition comprising the same. As a DNA repair enzyme poly (ADP-ribozyme) polymerase inhibitor, the compound and the pharmaceutical composition can effectively treat diseases involving PARP enzymatic activity, including cancer, neural degenerative diseases, inflammation and the like.


Patent
Chengdu Diao Pharmaceutical Group Co. | Date: 2014-11-05

Disclosed are a phthalic hydrazide (phthalazine ketone) compound, and a pharmaceutical composition comprising the same. As a DNA repair enzyme poly (ADP-ribozyme) polymerase inhibitor, the compound and the pharmaceutical composition can effectively treat diseases involving PARP enzymatic activity, including cancer, neural degenerative diseases, inflammation and the like.


Patent
Chengdu Diao Pharmaceutical Group Co. | Date: 2012-12-03

Disclosed are a phthalic hydrazide (phthalazine ketone) compound, and a pharmaceutical composition comprising the same. As a DNA repair enzyme poly (ADP-ribozyme) polymerase inhibitor, the compound and the pharmaceutical composition can effectively treat diseases involving PARP enzymatic activity, including cancer, neural degenerative diseases, inflammation and the like.

Loading Chengdu DiAo Pharmaceutical Group Co. collaborators
Loading Chengdu DiAo Pharmaceutical Group Co. collaborators