A guide to drug discovery: The role of the medicinal chemist in drug discovery — then and now

@article{Lombardino2004AGT,
  title={A guide to drug discovery: The role of the medicinal chemist in drug discovery — then and now},
  author={Joseph George Lombardino and John Lowe},
  journal={Nature Reviews Drug Discovery},
  year={2004},
  volume={3},
  pages={853-862}
}
The role of the medicinal chemist in drug discovery has undergone major changes in the past 25 years, mainly because of the introduction of technologies such as combinatorial chemistry and structure-based drug design. As medicinal chemists with more than 50 years of combined experience spanning the past four decades, we discuss this changing role using examples from our own and others' experience. This historical perspective could provide insights in to how to improve the current model for drug… Expand
The changing landscape of cancer drug discovery: a challenge to the medicinal chemist of tomorrow.
Since the development of the first cytotoxic agents, synthetic organic chemistry has advanced enormously. The synthetic and medicinal chemists of today are at the centre of drug development and areExpand
Teaser Modern medicinal chemistry impacts drug discovery in many ways beyond just optimization of clinical candidates
The role of medicinal chemistry has changed over the past 10 years. Chemistry had become one step in a process; funneling the output of highthroughput screening (HTS) on to the next stage. The goalExpand
Industrial medicinal chemistry insights: neuroscience hit generation at Janssen.
TLDR
It is shown how a successful medicinal chemistry team has a broad impact and requires multidisciplinary expertise in these areas, including new screening paradigms, computational approaches, novel synthetic chemistry, gene-family screening, investigating routes of delivery, and so on. Expand
Chapter 2 – The Drug Discovery Process: From Ancient Times to the Present Day
TLDR
The historical framework of the evolution of this process provides significant insight into how new drugs are discovered in the modern era, the role of key technologies, and how governmental oversight has impacted the pharmaceutical industry. Expand
Chemical Intuition in Drug Design and Discovery.
TLDR
An expert opinion is given on how chemical intuition contributes to the discovery of drugs, where it lies in the modern drug discovery process, and how multidisciplinary teams can create the optimal environment to drug design, discovery, and development. Expand
Drug discovery processes to drug targeting mechanisms
TLDR
The review will describe the preclinical stages, identification and validation of target through HTS (high throughput screening assay) and finally approval of drug molecule for further clinical development. Expand
Urea Derivatives in Modern Drug Discovery and Medicinal Chemistry.
TLDR
A broad overview of urea-based medicinally relevant compounds, ranging from approved drugs to recent medicinal chemistry developments, is provided, including outlines of traditional reagents and chemical procedures for the preparation of ureas. Expand
The influence of drug-like concepts on decision-making in medicinal chemistry
TLDR
Analysis of recent trends reveals that the physical properties of molecules that are currently being synthesized in leading drug discovery companies differ significantly from those of recently discovered oral drugs and compounds in clinical development. Expand
An historical overview of drug discovery.
TLDR
The third period has kick-started with an increase in biopharmaceutical drugs approved by FDA/EMEA for therapeutic use and the onset of the "Omics" revolution in the twenty-first century. Expand
The Medicinal Chemistry in the Era of Machines and Automation: Recent Advances in Continuous Flow Technology
TLDR
This Perspective highlights recent developments toward innovative medicinal chemistry strategies based on continuous flow systems coupled with automation and bioassays and describes equipment and representative examples of automated flow systems and end-to-end prototypes realized to expedite medicinal chemistry discovery cycles. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 49 REFERENCES
Structure-based drug design (SBDD): Every structure tells a story...
TLDR
The structure-based drug design approach (SBDD) is described, illustrating the way crystallographic information is utilized in an iterative manner to identify and optimize novel lead compounds, thereby accelerating the overall drug discovery process. Expand
The role of absorption, distribution, metabolism, excretion and toxicity in drug discovery.
TLDR
Fundamental concepts, key tools, reagents and experimental approaches used by the drug metabolism scientist to aid a modern project team in predicting human pharmacokinetics and assessing the "drug-like" molecule are discussed. Expand
Fulfilling the promise: drug discovery in the post-genomic era.
TLDR
The genomic era has brought with it a basic change in experimentation, enabling researchers to look more comprehensively at biological systems, and the consolidation of these emerging functional genomics and drug discovery technologies promises to reap the fruits of the genomic revolution. Expand
Drug-like properties and the causes of poor solubility and poor permeability.
  • C. Lipinski
  • Chemistry, Medicine
  • Journal of pharmacological and toxicological methods
  • 2000
TLDR
There are currently about 10000 drug-like compounds, and true diversity does not exist in experimental combinatorial chemistry screening libraries because current ADME experimental screens are multi-mechanisms, and predictions get worse as more data accumulates. Expand
Glivec (STI571, imatinib), a rationally developed, targeted anticancer drug
TLDR
This work describes how this drug discovery programme led to the discovery and continuing development of Glivec (Gleevec in the United States), the first selective tyrosine-kinase inhibitor to be approved for the treatment of a cancer. Expand
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings.
TLDR
Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described and useful predictions are possible in closely related analog series when coupled with experimental thermodynamicsolubility measurements. Expand
3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency.
TLDR
Optimization of this 3-aminopyrrolidinone series of compounds led to significant increases in potency, providing 83 and 85, the most potent inhibitors of FTase in cells described to date. Expand
[Clinical psychopharmacology: the example of clozapine (Leponex)].
: Ever since clozapine was discovered, researchers have been attempted to answer the question of what makes it different and how to relate its many pharmacological actions to its clinical features.Expand
[Clinical psychopharmacology: the example of clozapine (Leponex)].
TLDR
Four main hypothesis have been proposed in an attempt to explain some or all for clozapine's atypical properties: selective blockade of mesolimbic dopamine function; D1, D2, D3 and D4 receptor blockade; 5-HT2 and D2 receptors blockade; Potent alpha 1 adrenergic blockade. Expand
3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents.
TLDR
In vivo 8e possesses activity consistent with an efficacious antipsychotic agent with less tendency to induce extrapyramidal side effects in man, and a combination of D2 receptor affinity and 5-HT2A/D2 ratio comparable to the atypical agent clozapine. Expand
...
1
2
3
4
5
...