A5089870426- Marine Toxins and Detection Methods
- Marine Sponges and Natural Products
- Oxidative Organic Chemistry Reactions
- Synthetic Organic Chemistry Methods
- Hypothalamic control of reproductive hormones
- Neuropeptides and Animal Physiology
- Cytokine Signaling Pathways and Interactions
- Protein Kinase Regulation and GTPase Signaling
- Pharmacological Receptor Mechanisms and Effects
- HIV/AIDS drug development and treatment
- Hepatitis C virus research
- Melanoma and MAPK Pathways
- Alkaloids: synthesis and pharmacology
- Receptor Mechanisms and Signaling
- Neuroendocrine regulation and behavior
- Hepatitis B Virus Studies
- Neuroscience of respiration and sleep
Jiangsu Hengrui Medicine (China)
2017-2022
The Ohio State University
2013-2016
A member of the Janus kinase (JAK) family, Tyrosine Kinase 2 (TYK2), is crucial in mediating various cytokine-signaling pathways such as interleukin-23 (IL23), interleukin-12 (IL12) and type I Interferons (IFN) which contribute to autoimmune disorders (e.g., psoriasis, lupus, inflammatory bowel disease). Thus, TYK2 represents an attractive target develop small-molecule therapeutics for treatment cytokine-driven diseases. Selective inhibition over other JAK isoforms critical achieve a...
An efficient synthesis of the C22–C40 domain azaspiracids is described. The synthetic route features a Nozaki–Hiyama–Kishi (NHK) coupling and chelation controlled Mukaiyama aldol reaction to access an acyclic intermediate double-intramolecular-hetero-Michael addition (DIHMA) provide FG-ring system bridged ketal.
Recently, targeting the G protein-biased signaling has emerged as an attractive therapeutic strategy for treating severe acute pain with potential to reduce side effect of traditional opioid drug. Herein, we describe discovery a highly potent μ-opioid receptor (MOR) agonist, SHR9352. This novel molecule exhibited excellent MOR activity and limited β-arrestin recruitment, well high selectivity over κ-opioid δ-opioid demonstrated robust in vivo efficacy displayed favorable pharmacokinetic...
The oxytocin receptor (OTR) plays a major role in the control of male sexual responses. Antagonists OTR have been reported to inhibit ejaculation animal models and serve as potential treatment for premature (PE). Herein, we describe novel scaffold featuring an aryl substituted 3-azabicyclo [3.1.0] hexane structure. lead compound, SHR1653, was shown be highly potent antagonist, which exhibited excellent selectivity over V1AR, V1BR, V2R. This molecule favorable pharmacokinetic profile across...
An efficient synthesis of the C1–C21 fragment azaspiracids-1 and −3 is described. This features a Nozaki–Hiyama–Kishi reaction to couple AB CD ring precursors formation THF-fused ABCD trioxadispiroketal system under thermodynamic conditions.
Abstract A convergent and stereoselective total synthesis of the previously assigned structure azaspiracid‐3 has been achieved by a late‐stage Nozaki–Hiyama–Kishi coupling to form C21−C22 bond with C20 configuration unambiguously established from l ‐(+)‐tartaric acid. Postcoupling steps involved oxidation an ynone, modified Stryker reduction alkyne, global deprotection, resulting C1 primary alcohol carboxylic The synthetic product matched naturally occurring mass spectrometry, but differed...
Capsid assembly modulators (CpAMs) represent a new class of antivirals targeting hepatitis B virus (HBV) core protein to disrupt the process. In this work, novel chemotype featuring fused heterocycle amide was discovered through pharmacophore exploration. Lead optimization resulted in compound 8 with an EC50 value 511 nM, and then methyl substitution on piperazine found improve vitro potency remarkably. Further SAR studies established key SHR5133, which showed high antiviral potency,...
Abstract A convergent and stereoselective total synthesis of the previously assigned structure azaspiracid‐3 has been achieved by a late‐stage Nozaki–Hiyama–Kishi coupling to form C21−C22 bond with C20 configuration unambiguously established from l ‐(+)‐tartaric acid. Postcoupling steps involved oxidation an ynone, modified Stryker reduction alkyne, global deprotection, resulting C1 primary alcohol carboxylic The synthetic product matched naturally occurring mass spectrometry, but differed...