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Search for "cyclopamine" in Full Text gives 5 result(s) in Beilstein Journal of Organic Chemistry.

Syntheses and medicinal chemistry of spiro heterocyclic steroids

  • Laura L. Romero-Hernández,
  • Ana Isabel Ahuja-Casarín,
  • Penélope Merino-Montiel,
  • Sara Montiel-Smith,
  • José Luis Vega-Báez and
  • Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

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  • progestogen activity, so it is employed in combination with ethinylestradiol in oral contraceptives [6]. Various steroidal spiro heterocycles serve as effective drugs for treating diverse pathologies. For example, cyclopamine (Figure 1) inhibits Hedgehog (HH) signaling by interacting with the 7-transmembrane
  •  2) [11]. In 2011, during the synthesis of cyclopamine analogues, the research group constructed a spirooxetane ring on an estrane backbone. The reaction of the spirooxirane of estrane derivative 3 with the anion of TBDPS-protected pentyn-5-ol introduced the pentynyl group, which upon removal of the
  • cyclopamine. Comparing the biological results of the compound with the activity of desmethylveramiline (a des-E analogue of cyclopamine) has suggested that the rigidity of the oxetane ring is crucial for the potency of compound 7 [12]. Spiro-β-lactone steroids Beller et al. reported a selective method for
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Published 24 Jul 2024

C–H-Functionalization logic guides the synthesis of a carbacyclopamine analog

  • Sebastian Rabe,
  • Johann Moschner,
  • Marina Bantzi,
  • Philipp Heretsch and
  • Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 1564–1569, doi:10.3762/bjoc.10.161

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  • States 10.3762/bjoc.10.161 Abstract The chemical synthesis of carbacyclopamine analog 2, a cyclopamine analog with an all-carbon E-ring, is reported. The use of C–H-functionalization logic and further metal-catalyzed transformations allows for a concise entry to this new class of acid-stable cyclopamine
  • analogs. Keywords: cyclopamine; C–H-functionalization; hedgehog signaling pathway; natural products; steroidal alkaloids; Introduction The isolation of cyclopamine (1, Figure 1) nearly 50 years ago followed by the determination of its biological target and pharmacological profile has drawn considerable
  • interest from research groups in biology, chemistry and medicine [1][2][3][4]. As the first identified hedgehog signaling inhibitor, cyclopamine exerts its anticancer activity through a novel mechanism of action, which manifests itself in its remarkable activity against several types of human cancer
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Published 09 Jul 2014

Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1–DNA-complex formation

  • Midori A. Arai,
  • Kyoko Uchida,
  • Samir K. Sadhu,
  • Firoj Ahmed and
  • Masami Ishibashi

Beilstein J. Org. Chem. 2014, 10, 134–140, doi:10.3762/bjoc.10.10

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  • of tumors such as basal-cell carcinomas and small-cell lung cancer [5][6][7]. To find a drug for the treatment of cancer, Hh inhibitors have been recently developed. SMO inhibitors are a major category of Hh signaling inhibitors (cyclopamine [8][9], Cur-61414 [10] and SANTs [11]). Robotnikinin
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Published 13 Jan 2014

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

  • Johann Moschner,
  • Anna Chentsova,
  • Nicole Eilert,
  • Irene Rovardi,
  • Philipp Heretsch and
  • Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

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  • 77030, USA 10.3762/bjoc.9.267 Abstract The chemical synthesis and biological evaluation of new cyclopamine analogs bearing exocyclic methylenes in different positions is described. Bis-exo-cyclopamine 6 was identified as a potent inhibitor of the Gli1-dependent luciferase expression in Shh-LIGHTII
  • cells. An extension of this study to F-ring-modified structures shows the necessity of a rigidly positioned nitrogen atom for bioactivity as well as the presence of the C21 methyl group for acid stability and bioactivity. Keywords: cyclopamine; hedgehog signaling pathway; natural products; steroidal
  • ], lymphoma [17][18][19], multiple myeloma [17][20], and chronic myeloic leukemia [21][22][23]. More recently, other diseases like diabetes [24][25], neurodegenerative disorders [26], and trisomy [27][28], have been linked with hedgehog signaling. Cyclopamine (1, see Figure 1) was the first inhibitor of the
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Published 31 Oct 2013

Synthesis and characterization of Sant-75 derivatives as Hedgehog-pathway inhibitors

  • Chao Che,
  • Song Li,
  • Bo Yang,
  • Shengchang Xin,
  • Zhixiong Yu,
  • Taofeng Shao,
  • Chuanye Tao,
  • Shuo Lin and
  • Zhen Yang

Beilstein J. Org. Chem. 2012, 8, 841–849, doi:10.3762/bjoc.8.94

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  • human diseases, intense efforts have been invested to identify therapeutic inhibitors acting on the Smo protein. Cyclopamine (Figure 1), a natural alkaloid isolated from Veratrum californicum [12][13], was disclosed as the first small molecule inhibitor of the Hh pathway through direct interaction with
  • Smo [14][15]. Cyclopamine can effectively induce a decrease in proliferation and an increase of apoptosis in several murine models [16][17]. However, the clinical development of cyclopamine as a therapeutic in cancer is hampered by its poor aqueous solubility (ca. 5 µg/mL) and acid lability
  • . Subsequently, Infinity Pharmaceuticals developed cyclopamine-based Smo inhibitors IPI-926 through structural modification on the A and D rings. IPI-926 exhibited improved pharmaceutical properties as well as a favorable pharmacokinetic profile, and showed complete tumor regression in a Hh-dependent
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Published 06 Jun 2012
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