205678-31-5 Usage
Biological Activity
sb 273005 is a potent nonpeptide antagonist of αvβ3 (vitronectin receptor), with ki values of 1.2 nm and 0.3 nm to two closely related integrins, αvβ3 and αvβ5, respectively [1].αvβ3 belongs to the integrin family of adhesion molecules. it is a heterodimer. it mediates cell adhesion to serum proteins and extracellular matrix via the recognition of the arg-gly-asp (rgd) sequence [1].sb 273005 binds αvβ3 and αvβ5 with low nm affinity, but binds weakly to integrins αiibβ3 and α5β1. sb 273005 inhibits αvβ3-mediated cell adhesion with an ic50 value of 3 nm, endothelial cell migration with an ic50 of 1.8 nm, and osteoclast-mediated bone resorption with an ic50 of 11 nm in vitro [1].the αvβ3 integrin is pivotal in bone resorption [2]. in the chronic ovx and thyroparathyroidectomized bone resorption rat models, sb 273005 as well as other similar vitronectin receptor antagonists, inhibit bone loss. in aia rats, prophylactical treatment with sb 273005 at doses of 60, 30, and 10 mg/kg twice daily significantly normalized bone mineral density (bmd). normalization values of bmd were 69%, 42%, and 44% for doses of 60, 30, and 10 mg/kg twice daily, respectively. a single daily dose of sb 273005 significantly improved bmd (24% normalization) only when sb 273005 was prophylactically administered at 60 mg/kg [1].
references
[1]. badger am, blake s, kapadia r, et al. disease-modifying activity of sb 273005, an orally active, nonpeptide αvβ3 (vitronectin receptor) antagonist, in rat adjuvant-induced arthritis. arthritis & rheumatism, 2001, 44(1): 128-137.[2]. murphy mg, cerchio k, stoch sa, et al. effect of l-000845704, an αvβ3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women. the journal of clinical endocrinology & metabolism, 2005, 90(4): 2022-2028.
Check Digit Verification of cas no
The CAS Registry Mumber 205678-31-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,0,5,6,7 and 8 respectively; the second part has 2 digits, 3 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 205678-31:
(8*2)+(7*0)+(6*5)+(5*6)+(4*7)+(3*8)+(2*3)+(1*1)=135
135 % 10 = 5
So 205678-31-5 is a valid CAS Registry Number.
205678-31-5Relevant articles and documents
Multi-kiloscale enantioselective synthesis of a vitronectin receptor antagonist
Wallace, Michael D.,McGuire, Michael A.,Yu, Marvin S.,Goldfinger, Lynn,Liu, Li,Dai, Wenning,Shilcrat, Susan
, p. 738 - 743 (2004)
The development of a novel, cost-effective synthesis of the vitronectin receptor antagonist SB-273005 became necessary as the compound proceeded to Phase 1. A practical synthesis of the compound presented challenges to the process chemist. Chief among the challenges was developing an enantioselective route to the compound. Second was either developing a scalable Mitsunobu coupling of the side chain to the main body or finding alternate chemistry. In this paper we will describe the chemistry we developed which allowed us to make over a hundred kilograms of SB-273005 by a process that we believe is suitable for even larger scale manufacturing.
Vitronectin receptor antagonists
-
, (2008/06/13)
Compounds having a benzodiazepinyl core structure are disclosed which are vitronectin receptor antagonists useful in the treatment of osteoporosis, angiogenesis, tumor growth and metastasis, atherosclerosis, restenosis and inflammation.
