Rational changes in the substituent

Rational changes in the substituents in both rings and
alteration of the length and rigidity of the linker gave rise to
PU24FCl (108; Scheme 19), which, although not the most
active in the series, was utilized to further investigate Hsp90
inhibition in both healthy and tumor cells. The extensive
effects exhibited by both healthy and tumor tissues when
exposed to the compound have been reported, and, as with
17-AAG and GA, PU24FCl exhibited at least 10- (brain,
pancreas, lung) to 50-fold (heart, kidney, liver) lower affinity
for Hsp90s from healthy tissues as compared with those from
transformed cells. Later studies have shown that replacement
of the methylene bridge with sulfur gives 8-arylsulfanyl
adenine derivatives (e.g., 109; Scheme 19) of greater
potency, while introduction of an ionizable amino group
in the N(9) side chain improved both the water solubility
and potency of the compounds to give orally active agents
(e.g., 110; Scheme 19). Finally, by extending the Chiosis
concept further, Conforma (now Biogen-Idec) scientists
derived CNF2024 (111; Scheme 19) which is now in phase
II clinical trials

ผลลัพธ์ (ไทย) 3:

Rational changes in the substituents in both rings and
alteration of the length and rigidity of the linker gave rise to
PU24FCl (108; Scheme 19), which, although not the most
active in the series, was utilized to further investigate Hsp90
inhibition in both healthy and tumor cells. The extensive
effects exhibited by both healthy and tumor tissues when
exposed to the compound have been reported,และ กับและ pu24fcl
17-aag GA จัดแสดงอย่างน้อย 10 - ( สมอง
ตับอ่อน , ปอด ) ถึง 50 เท่า ( หัวใจ , ไต , ตับ ) ลด affinity
สำหรับ hsp90s จากเนื้อเยื่อสุขภาพเมื่อเทียบกับผู้ที่มาจาก
เปลี่ยนเซลล์ การศึกษาต่อมาพบว่าแทน
ของเมทธิลีนสะพานด้วยกำมะถันให้ 8-arylsulfanyl
และอนุพันธ์ ( เช่น 109 ; โครงการ 19 ) มากกว่า
แรง , while introduction of an ionizable amino group
in the N(9) side chain improved both the water solubility
and potency of the compounds to give orally active agents
(e.g., 110; Scheme 19). Finally, by extending the Chiosis
concept further, Conforma (now Biogen-Idec) scientists
derived CNF2024 (111; Scheme 19) which is now in phase
II clinical trials