17,20-Lyase inhibitors. Part 3: Design, synthesis, and structure–activity relationships of biphenylylmethylimidazole derivatives as novel 17,20-lyase inhibitors

Kaku, Tomohiro; Tsujimoto, Saori; Matsunaga, Nobuyuki; Tanaka, Toshimasa; Hara, Takahito; Yamaoka, Masuo; Kusaka, Masami; Tasaka, Akihiro

doi:10.1016/j.bmc.2011.02.009

Cited by 9 publications

(7 citation statements)

References 48 publications

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“…Especially, the isopropyl derivative 28b could significantly decrease both serum testosterone and dehydroepiandrosterone concentrations after oral administration in a monkey model. This result suggested the important influence of chiral configuration in regulating the biological activity and selectivity . These nonsteroidal imidazole CYP inhibitors provide meaningful insights in the development of potent drugs against prostate cancer.…”

Section: Imidazoles As Anticancer Agentsmentioning

confidence: 77%

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

et al. 2013

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Imidazole ring is an important five-membered aromatic heterocycle widely present in natural products and synthetic molecules. The unique structural feature of imidazole ring with desirable electron-rich characteristic is beneficial for imidazole derivatives to readily bind with a variety of enzymes and receptors in biological systems through diverse weak interactions, thereby exhibiting broad bioactivities. The related research and developments of imidazole-based medicinal chemistry have become a rapidly developing and increasingly active topic. Particularly, numerous imidazole-based compounds as clinical drugs have been extensively used in the clinic to treat various types of diseases with high therapeutic potency, which have shown the enormous development value. This work systematically gives a comprehensive review in current developments of imidazole-based compounds in the whole range of medicinal chemistry as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents, together with their potential applications in diagnostics and pathology. It is hoped that this review will be helpful for new thoughts in the quest for rational designs of more active and less toxic imidazole-based medicinal drugs, as well as more effective diagnostic agents and pathologic probes.

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Section: Imidazoles As Anticancer Agentsmentioning

confidence: 77%

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

et al. 2013

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“…Compound 32a Fig. (32) exhibited a moderate CYP3A4 liability of 1.2 μM (Table 30) [40]. Modifications on the biphenyl moiety (32b and 32c) led to significant improvement in the CYP profile (32b: IC 50 7.6 μM, 32c: IC 50 >10 μM).…”

Section: Case VImentioning

confidence: 98%

Modulation of Cytochrome-P450 Inhibition (CYP) in Drug Discovery: A Medicinal Chemistry Perspective

Kumar¹,

Sharma²,

Roychowdhury

2012

CMC

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Cytochrome P450 (CYP450) has widely been implicated for drug-drug interactions (DDI) in the pharmaceutical industry. Inhibition or induction of this enzyme family has led to withdrawal of multiple drugs from the market leading to major time and financial losses for the pharmaceutical industry. CYP450 plays a prevailing role in the biotransformation of a large number of structurally diverse drugs. Few isoenzymes of the CYP enzyme family (CYP3A4, 2D6 and 2C9 family) are mainly involved in metabolism of most of the drugs. To avoid such interactions and potentially minimize DDI, major pharmaceutical organizations prefer to incorporate CYP enzyme screening at an early stage of their discovery program. While this has been a prevalent practice in the pharmaceutical industry lately, there is very limited literature available reviewing the relationship between chemotypes and CYP isoforms. This review will collate literature pertaining to CYP-inhibition modulation through physicochemical parameters and chemical modification and thus bring to focus commonly used trends by medicinal chemists world-wide.

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“…The dextrorotatory enantiomer was over 10 times less potent (IC 50 = 340 nM vs 26 nM). Moreover, the compound displayed a sustained decrease in serum testosterone levels after single oral dosing …”

Section: Inhibitorsmentioning

confidence: 99%

Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment

et al. 2023

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CYP17A1 is an enzyme that plays a major role in steroidogenesis and is critically involved in the biosynthesis of steroid hormones. Therefore, it remains an attractive target in several serious hormone-dependent cancer diseases, such as prostate cancer and breast cancer. The medicinal chemistry community has been committed to the discovery and development of CYP17A1 inhibitors for many years, particularly for the treatment of castration-resistant prostate cancer. The current Perspective reflects upon the discovery and evaluation of non-steroidal CYP17A1 inhibitors from a medicinal chemistry angle. Emphasis is placed on the structural aspects of the target, key learnings from the presented chemotypes, and design guidelines for future inhibitors.

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17,20-Lyase inhibitors. Part 3: Design, synthesis, and structure–activity relationships of biphenylylmethylimidazole derivatives as novel 17,20-lyase inhibitors

Cited by 9 publications

References 48 publications

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

Comprehensive Review in Current Developments of Imidazole-Based Medicinal Chemistry

Modulation of Cytochrome-P450 Inhibition (CYP) in Drug Discovery: A Medicinal Chemistry Perspective

Non-steroidal CYP17A1 Inhibitors: Discovery and Assessment

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