Small molecule inhibitors of androgen receptor n-terminal activation
A technology of androgen receptor, halogen, applied in the field of cancer therapy and treatment, which can solve the problems hindering the virtual docking drug development method and so on
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment approach
[0218] According to one embodiment, the method may comprise, for example and without limitation, compounding a compound of formula (Q):
[0219]
[0220] where R 25 as defined anywhere above,
[0221] mixed with n-BuLi to form a mixture, and reacting the mixture with a compound of formula (S),
[0222]
[0223] where R 26 as defined anywhere above and Prot is a protecting group,
[0224] to form compounds of formula (T):
[0225]
[0226] where R 25 and R 26 as defined anywhere above and Prot is a protecting group;
[0227] Compounds of formula (T) are deprotected to form compounds of formula (U):
[0228]
[0229] where R 25 and R 26 as defined anywhere above; and
[0230] A compound of formula (U) is reacted with a compound of formula (V) in pyridine to form a compound of formula (K):
[0231] (R 27 CO) 2 O(V)
[0232] where R 27 As defined anywhere above.
[0233] According to one embodiment, the compound of formula (Q) may be mixed with n-BuLi, ...
Embodiment 1
[0291] Example 1: Assay-guided fractionation and isolation of compounds
[0292] Using SCUBA, South Sea sponge (Dysideasp.) samples were collected by hand at a depth of about 15 m in June 2006 near Karimunjawa archipelago, Palau Sintok, Indonesia (N55°02.52, E119°19.48). Prof. Rob van Soest of the University of Amsterdam identified the sponge and deposited evidence samples at the Amsterdam Zoological Museum (ZMAPOR.20602).
[0293]Freshly collected gray sponges (140 g) were initially stored in MeOH and transported to Canada, British Columbia, Vancouver, Canada, over a period of 5 days at room temperature, after which samples were frozen. The sponge was cut into small pieces, immersed in MeOH and then extracted repeatedly with MeOH (3x200 mL). The combined methanol extracts were concentrated in vacuo and the resulting oil was then dissolved in EtOAc (4x5 mL) and H 2 O (20mL). The combined EtOAc extracts were evaporated to dryness and the purple oil obtained was chromatograph...
Embodiment 2
[0309] Example 2: Synthesis of N-((R)-1-((S)-2-isobutyl-3-methoxy-5-oxo-2,5-dihydro-1H-pyrrol-1-yl )-4-methyl-1-oxopent-2-yl)propionamide
[0310] N-phthalimide-L-leucine (1).
[0311]
[0312]
[0313] L-leucine (5.12g, 39.1mmol) and Na 2 CO 3 (4.14g, 39.1mmol) dissolved in 40mL distilled H 2O middle. The solution was added to N-ethoxyformyl-phthaloyl (8.55 g, 39.1 mmol), and then stirred at room temperature for 2 hours. The resulting clear solution was acidified to pH = 0 using 6N HCl, then extracted with hexane (3 x 100 mL). The combined layers were vacuum dried. Apply silica gel column chromatography, eluting with hexane / acetone (3:1), obtain N-phthalimide-L-leucine (1) (10.2g, 39.1mmol, quantitative), as free color oil. 1 HNMR (400MHz, CDCl 3 )δ0.92(d, J=6.70Hz, 3H), 0.94(d, J=6.70Hz, 3H), 1.37-1.60(m, 1H), 1.95(ddd, J=14.31, 10.05, 4.26Hz, 1H ), 2.36 (ddd, J=14.31, 10.05, 4.26Hz, 1H), 4.99 (dd, J=11.57, 4.26Hz, 1H), 7.73 (dd, J=5.48, 3.05Hz, 2H), 7.85 (dd...
PUM
Login to View More Abstract
Description
Claims
Application Information
Login to View More