Simple Bi- and tricyclic inhibitors of human steroid 5α-reductase

Abell, Andrew D.; Prince, Maureen J.; McNulty, Ann M.; Neubauer, Blake Lee

doi:10.1016/s0960-894x(00)00368-1

Cited by 10 publications

(3 citation statements)

References 13 publications

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“…(28)) [64]. functionality of the tricyclic analogues has been investigated by A.D. Abell [65,66]. The obtained results indicate that tricyclic thiolactams (47) (IC 50 type 1 = 377 nM, type 2 = 40 µM) and (49) (IC 50 type 1 = 183 nM, type 2 = 40 µM) are, like their lactam analogues, selective for type 1 steroid 5α-reductase.…”

Section: Benzo[c]quinolizinonesmentioning

confidence: 99%

Trends in the Development of New Drugs for Treatment of Benign Prostatic Hyperplasia

Kulig¹,

Malawska

2006

CMC

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Benign prostatic hyperplasia (BPH) is a common condition in aging men that is characterized by nonmalignant enlargement of the prostate gland, and is frequently accompanied by urinary obstruction, and lower urinary tract symptoms (LUST). Currently pharmacotherapy of BPH is based on two classes of drugs: alpha(1)-adrenoceptor (alpha(1)-AR) antagonists and 5alpha-reductase inhibitors. It has been shown that alpha(1)-AR antagonists reduce symptom scores and increase peak urinary flow rates in BPH. Of particular importance for BPH therapy are uroselective alpha(1)-AR antagonists for which the hypotensive related side-effect caused by alpha(1)-AR blockade is reduced. 5alpha-Reductase inhibitors reduce prostate volume and symptom scores, while increasing peak urinary flow rates. This review describes new alpha(1)-AR antagonists and 5alpha-reductase inhibitors in the treatment of BPH. The new alpha(1)-AR antagonists represent various structures such as quinazolines, phenylethylamines, piperidines, and arylpiperazines. 5alpha-Reductase inhibitors are classified into two groups: steroidal and non-steroidal. The newer non-steroidal inhibitors include derivatives of benzo[c]quinolizinones, benzo[f]quinolonones, piperidones and carboxylic acids. Besides the development of new compounds belonging to the above mentioned groups, new agents for BPH treatment are sought among combined 5alpha-reductase/alpha(1)-AR inhibitors, endothelins, androgen receptors antagonists, growth factors, estrogens and phosphodiesterase isoenzymes as well as several phytomedicines, used for prevention and treatment of prostate disorders. These new agents can be used for the design of future targets and development of new drugs in the treatment of BPH. The discovery of a number of active leads may also ultimately help in developing new safe and effective drugs.

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Section: Benzo[c]quinolizinonesmentioning

confidence: 99%

Trends in the Development of New Drugs for Treatment of Benign Prostatic Hyperplasia

Kulig¹,

Malawska

2006

CMC

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“…For example, compounds 6a-b (Table 2), lacking the B and D steroidal rings, were only poor 5␣R-1 inhibitors, with the highest potency associated to the presence of the Cl atom on the aromatic ring of 6b (IC 50 = 1690 nM) [53]. Similarly, pyridones 8 and 9 (n = 1,2; X = CON(i-Pr) 2 ; R 1 , R 2 = H,Me) where the B and C rings of the steroid system have been replaced by an acyclic linker display relatively weak activity versus both 5␣-R isozymes [54][55][56].…”

Section: Piperidones Quinolinones and Pyridonesmentioning

confidence: 99%

Selective non-steroidal inhibitors of 5α-reductase type 1

Occhiato

Guarna

Danza

et al. 2004

The Journal of Steroid Biochemistry and Molecular Biology

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“…The identification of 3-arylpiperidines as inhibitors of the steroid 5α-reductase, as ligands of the σ receptor, and as antagonists of the tachykinin system increases their importance as a class with privileged pharmacological structures. Thus, piperidone UK-224,671 is a potent, selective antagonist of the neurokinin 2 receptor, while MK-4827 developed by Merck has entered clinical trials as an antitumor drug (Figure ) …”

mentioning

confidence: 99%

Desulfonylative Radical Ring Closure onto Aromatics. A Modular Route to Benzazepin-2-ones and 5-Arylpiperidin-2-ones

2012

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Adducts from the intermolecular radical addition of N-xanthylacetyl-N-methanesulfanilides to Boc-protected allylamine undergo ring closure with loss of a methanesulfonyl radical to give benzazepin-2-ones. Upon deprotection and exposure to triethylamine, these compounds rearrange into 5-aryl-2-piperidones. This approach also represents a useful route to benzazepin-2-ones unsubstituted on the nitrogen atom of the azepinone ring.

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Simple Bi- and tricyclic inhibitors of human steroid 5α-reductase

Cited by 10 publications

References 13 publications

Trends in the Development of New Drugs for Treatment of Benign Prostatic Hyperplasia

Trends in the Development of New Drugs for Treatment of Benign Prostatic Hyperplasia

Selective non-steroidal inhibitors of 5α-reductase type 1

Desulfonylative Radical Ring Closure onto Aromatics. A Modular Route to Benzazepin-2-ones and 5-Arylpiperidin-2-ones

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