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• 1126084-29-4 benzyl 4-(2-hydroxy-2-methylpropyl)piperidine-1-carboxylate 

Relevant academic research and scientific papers

PYRIDIN-3-YL ACETIC ACID DERIVATIVES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS REPLICATION

Disclosed are compounds of Formula I, including pharmaceutically acceptable salts, pharmaceutical compositions comprising the compounds, methods for making the compounds and their use in inhibiting HIV integrase and treating those infected with HIV or AIDS.

Discovery of 2-methyl-1-{1-[(5-methyl-1H-indol-2-yl)carbonyl]piperidin-4- yl}propan-2-ol: A novel, potent and selective type 5 17β-hydroxysteroid dehydrogenase inhibitor

Type 5 17β-hydroxysteroid dehydrogenase (17β-HSD5), also known as aldo-keto reductase 1C3 (AKR1C3), is a member of the aldo-keto reductase superfamily of enzymes and is expressed in the human prostate. One of the main functions of 17β-HSD5 is to catalyze the conversion of the weak androgen, androstenedione, to the potent androgen, testosterone. The concentration of intraprostatic 5α-dihydrotestosterone (DHT) in patients following chemical or surgical castration has been reported to remain as high as 39% of that of healthy men, with 17β-HSD5 shown to be involved in this androgen synthesis. Inhibition of 17β-HSD5 therefore represents a promising target for the treatment of castration-resistant prostate cancer (CRPC). To investigate this, we conducted high-throughput screening (HTS) and identified compound 2, which displayed a structure distinct from known 17β-HSD5 inhibitors. To optimize the inhibitory activity of compound 2, we first introduced a primary alcohol group. We then converted the primary alcohol group to a tertiary alcohol, which further enhanced the inhibitory activity, improved metabolic stability, and led to the identification of compound 17. Oral administration of compound 17 to castrated nude mice bearing the CWR22R xenograft resulted in the suppression of androstenedione (AD)-induced intratumoral testosterone production. Compound 17 also demonstrated good isoform selectivity, minimal inhibitory activity against either CYP or hERG, and enhanced pharmacokinetic and physicochemical properties.

PIPERIDINE DERIVATIVE

As a result of studies on compounds having a selective inhibitory activity against 17βHSD type 5, the present inventors have confirmed that a {1-[(indol-2-yl)carbonyl]piperidyl}alkanol derivative has a potent selective inhibitory activity against 17βHSD type 5. The invention has been completed based on these findings. The compound of the present invention can be used as an agent for treating and/or an agent for preventing diseases associated with 17βHSD type 5, such as benign prostatic hyperplasia and prostate cancer, without accompanying adverse effects due to a decrease in testosterone.

4-alkyl piperidinyl pyrrolidine modulators of chemokine receptor activity

The present invention is directed to pyrrolidine compounds of the formula I: (wherein R1, R2, R3, R4c, R4d, and R4f are defined herein) which are useful as modulators of chemokine receptor activity. In particular, these compounds are useful as modulators of the chemokine receptors CCR-3 and/or CCR-5.