Tianying Jian

Publications (10)43.7 Total impact

• Article: Discovery of highly potent and efficacious MC4R agonists with spiroindane N-Me-1,2,4-triazole privileged structures for the treatment of obesity.

  Shuwen He, Zhixiong Ye, Peter H Dobbelaar, Raman K Bakshi, Qingmei Hong, James P Dellureficio, Iyassu K Sebhat, Liangqin Guo, Jian Liu, Tianying Jian, [......], Constantin Tamvakopoulos, Qianping Peng, Randy R Miller, Ralph A Stearns, Howard Y Chen, Airu S Chen, Alison M Strack, Tung M Fong, Matthew J Wyvratt, Ravi P Nargund
  [show abstract] [hide abstract]
  ABSTRACT: We report an SAR study of MC4R analogs containing spiroindane heterocyclic privileged structures. Compound 26 with N-Me-1,2,4-triazole moiety possesses exceptional potency at MC4R and potent anti-obesity efficacy in a mouse model. However, the efficacy is not completely mediated through MC4R. Additional SAR studies led to the discovery of compound 32, which is more potent at MC4R. Compound 32 demonstrates MC4R mediated anti-obesity efficacy in rodent models.
  Bioorganic & medicinal chemistry letters 09/2010; 20(22):6524-32. · 2.65 Impact Factor
• Article: Discovery of potent, selective, and orally bioavailable 3H-spiro[isobenzofuran-1,4'-piperidine] based melanocortin subtype-4 receptor agonists.

  Liangqin Guo, Zhixiong Ye, Jian Liu, Shuwen He, Raman K Bakshi, Iyassu K Sebhat, Peter H Dobbelaar, Qingmei Hong, Tianying Jian, James P Dellureficio, [......], Constantin Tamvakopoulos, Qianping Peng, Howard Y Chen, Airu S Chen, William J Martin, D Euan MacIntyre, Alison M Strack, Tung M Fong, Matthew J Wyvratt, Ravi P Nargund
  [show abstract] [hide abstract]
  ABSTRACT: Design, synthesis, and SAR of a series of 3H-spiro[isobenzofuran-1,4'-piperidine] based compounds as potent, selective and orally bioavailable melanocortin subtype-4 receptor (MC4R) agonists are disclosed.
  Bioorganic & medicinal chemistry letters 08/2010; 20(16):4895-900. · 2.65 Impact Factor
• Article: Optimization of privileged structures for selective and potent melanocortin subtype-4 receptor ligands.

  Qingmei Hong, Raman K Bakshi, James Dellureficio, Shuwen He, Zhixiong Ye, Peter H Dobbelaar, Iyassu K Sebhat, Liangqin Guo, Jian Liu, Tianying Jian, [......], Willian J Martin, Airu S Chen, Joseph M Metzger, Howard Y Chen, Allison M Strack, Tung M Fong, Euan Maclntyre, Lex H T Van der Ploeg, Matthew J Wyvratt, Ravi P Nargund
  [show abstract] [hide abstract]
  ABSTRACT: Design, syntheses and structure-activity relationships of N-acetylated piperazine privileged structures containing MC4R agonist compounds were described. The most potent derivatives were low nM MC4R selective full agonists. Several compounds from the series had modest pharmacokinetic properties.
  Bioorganic & medicinal chemistry letters 08/2010; 20(15):4483-6. · 2.65 Impact Factor
• Article: Spiroindane based amides as potent and selective MC4R agonists for the treatment of obesity.

  Shuwen He, Zhixiong Ye, Peter H Dobbelaar, Iyassu K Sebhat, Liangqin Guo, Jian Liu, Tianying Jian, Yingjie Lai, Christopher L Franklin, Raman K Bakshi, [......], Alison M Strack, Constantin Tamvakopoulos, Qianping Peng, Randy R Miller, Ralph A Stearns, Howard Y Chen, Airu S Chen, Tung M Fong, Matthew J Wyvratt, Ravi P Nargund
  [show abstract] [hide abstract]
  ABSTRACT: We report a series of potent and selective MC4R agonists based on spiroindane amide privileged structures for potential treatments of obesity. Among the synthetic methods used, Method C allows rapid synthesis of the analogs. The series of compounds can afford high potency on MC4R as well as good rodent pharmacokinetic profiles. Compound 1r (MK-0489) demonstrates MC4R mediated reduction of food intake and body weight in mouse models. Compound 1r is efficacious in 14-day diet-induced obese (DIO) rat models.
  Bioorganic & medicinal chemistry letters 08/2010; 20(15):4399-405. · 2.65 Impact Factor
• Article: Regulation of energy homeostasis by bombesin receptor subtype-3: selective receptor agonists for the treatment of obesity.

  Xiao-Ming Guan, Howard Chen, Peter H Dobbelaar, Yan Dong, Tung M Fong, Karen Gagen, Judith Gorski, Shuwen He, Andrew D Howard, Tianying Jian, [......], Lauren Shearman, Zhu Shen, Ralph Stearns, Alison M Strack, Sloan Stribling, Yui Sing Tang, Sheng-Ping Wang, Amanda White, Hong Yu, Marc L Reitman
  [show abstract] [hide abstract]
  ABSTRACT: Bombesin receptor subtype 3 (BRS-3) is a G protein coupled receptor whose natural ligand is unknown. We developed potent, selective agonist (Bag-1, Bag-2) and antagonist (Bantag-1) ligands to explore BRS-3 function. BRS-3-binding sites were identified in the hypothalamus, caudal brainstem, and several midbrain nuclei that harbor monoaminergic cell bodies. Antagonist administration increased food intake and body weight, whereas agonists increased metabolic rate and reduced food intake and body weight. Prolonged high levels of receptor occupancy increased weight loss, suggesting a lack of tachyphylaxis. BRS-3 agonist effectiveness was absent in Brs3(-/Y) (BRS-3 null) mice but was maintained in Npy(-/-)Agrp(-/-), Mc4r(-/-), Cnr1(-/-), and Lepr(db/db) mice. In addition, Brs3(-/Y) mice lost weight upon treatment with either a MC4R agonist or a CB1R inverse agonist. These results demonstrate that BRS-3 has a role in energy homeostasis that complements several well-known pathways and that BRS-3 agonists represent a potential approach to the treatment of obesity.
  Cell metabolism 02/2010; 11(2):101-12. · 17.35 Impact Factor
• Article: Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists.

  Shuwen He, Peter H Dobbelaar, Jian Liu, Tianying Jian, Iyassu K Sebhat, Linus S Lin, Allan Goodman, Cheng Guo, Peter R Guzzo, Mark Hadden, [......], Scott D Feighner, Carina Tan, Andrew D Howard, Constantin Tamvakopoulos, Qianping Peng, Xiao-Ming Guan, Marc L Reitman, Arthur A Patchett, Matthew J Wyvratt, Ravi P Nargund
  [show abstract] [hide abstract]
  ABSTRACT: We report SAR studies on a novel non-peptidic bombesin receptor subtype-3 (BRS-3) agonist lead series derived from high-throughput screening hit RY-337. This effort led to the discovery of compound 22e with significantly improved potency at both rodent and human BRS-3.
  Bioorganic & medicinal chemistry letters 02/2010; 20(6):1913-7. · 2.65 Impact Factor
• Article: Discovery of a spiroindane based compound as a potent, selective, orally bioavailable melanocortin subtype-4 receptor agonist.

  Shuwen He, Zhixiong Ye, Peter H Dobbelaar, Iyassu K Sebhat, Liangqin Guo, Jian Liu, Tianying Jian, Yingjie Lai, Christopher L Franklin, Raman K Bakshi, [......], Qianping Peng, Randy R Miller, Ralph A Stearns, Howard Y Chen, Airu S Chen, Alison M Strack, Tung M Fong, D Euan Macintyre, Matthew J Wyvratt, Ravi P Nargund
  [show abstract] [hide abstract]
  ABSTRACT: We report the design, synthesis and properties of spiroindane based compound 1, a potent, selective, orally bioavailable, non-peptide melanocortin subtype-4 receptor agonist. Compound 1 shows excellent erectogenic activity in the rodent models.
  Bioorganic & medicinal chemistry letters 02/2010; 20(7):2106-10. · 2.65 Impact Factor
• Article: Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity.

  Jian Liu, Shuwen He, Tianying Jian, Peter H Dobbelaar, Iyassu K Sebhat, Linus S Lin, Allan Goodman, Cheng Guo, Peter R Guzzo, Mark Hadden, [......], Yanqing Kan, Oksana Palyha, Theresa M Kelly, Xiao-Ming Guan, Andrew D Howard, Donald J Marsh, Joseph M Metzger, Marc L Reitman, Matthew J Wyvratt, Ravi P Nargund
  [show abstract] [hide abstract]
  ABSTRACT: This Letter describes a series of potent and selective BRS-3 agonists containing a biarylethylimidazole pharmacophore. Extensive SAR studies were carried out with different aryl substitutions. This work led to the identification of a compound 2-{2-[4-(pyridin-2-yl)phenyl]ethyl}-5-(2,2-dimethylbutyl)-1H-imidazole 9 with excellent binding affinity (IC(50)=18 nM, hBRS-3) and functional agonist activity (EC(50)=47 nM, 99% activation). After oral administration, compound 9 had sufficient exposure in diet induced obese mice to demonstrate efficacy in lowering food intake and body weight via BRS-3 activation.
  Bioorganic & medicinal chemistry letters 02/2010; 20(7):2074-7. · 2.65 Impact Factor
• Article: Synthesis and antibacterial activity of a novel class of 4'-substituted 16-membered ring macrolides derived from tylosin.

  Ly T Phan, Tianying Jian, Zhigang Chen, Yao-Ling Qiu, Zhaolin Wang, Theresa Beach, Alex Polemeropoulos, Yat Sun Or
  [show abstract] [hide abstract]
  ABSTRACT: Novel 4'-substituted 16-membered ring macrolides were synthesized by the cleavage of the mycarose sugar of tylosin and subsequent modification of 4'-hydroxyl group. This new class of macrolide antibiotics exhibited potent activity against some key erythromycin-resistant pathogens.
  Journal of Medicinal Chemistry 07/2004; 47(12):2965-8. · 5.25 Impact Factor
• Article: Synthesis of novel 4'-substituted 16-membered ring macrolide antibiotics derived from leucomycins.

  Zhaolin Wang, Tianying Jian, Ly T Phan, Yat Sun Or
  [show abstract] [hide abstract]
  ABSTRACT: A series of novel 4'-substituted 16-membered ring macrolides was synthesized by the cleavage of the mycarose sugar and subsequent modification of 4'-hydroxyl group. This new class of macrolides antibiotics is acid stable. The synthetic methodology described here is expected to find application in the synthesis of new generation of macrolides that target the emerging bacterial resistance.
  Bioorganic & Medicinal Chemistry Letters 02/2004; 14(2):519-21. · 2.55 Impact Factor