Pii: S0968-0896(99)00045-0
نویسندگان
چکیده
ÐConjugates of bisphosphonates (potential bone resorption inhibitors) and prostaglandin E2 (a bone formation enhancer) were prepared and evaluated for their ability to bind to bone and to liberate, enzymatically, free PGE2. The conjugate 3, an amide at C-1 of PGE2 proved to be too stable in vivo while conjugate 6, a thioester, was too labile. Several PGE2, C-15 ester-linked conjugates (18, 23, 24 and 31) were prepared and conjugate 23 was found to bind eectively to bone in vitro and in vivo and to liberate PGE2 at an acceptable rate. A 4-week study in a rat model of osteoporosis showed that 23 was better tolerated and more eective as a bone growth stimulant than daily maximum tolerated doses of free PGE2. # 1999 Elsevier Science Ltd. All rights reserved.
منابع مشابه
Pii: S0968-0896(99)00042-5
ÐUtilization of 17-keto-androstanes as starting materials for the synthesis of aor b-oriented steroidal 20!16-g-carbolactones has been explored following two dierent strategies. A highly ecient, stereospeci®c protocol has been developed for the boriented cis-g-lactone. A dierent approach, involving prior attachment of a 3-carbon side chain on C-17 of a 17-oxo-16b-acetoxyandrostane led to the...
متن کاملPii: S0968-0896(97)00137-5
-Philanthotoxins are noncompetitive inhibitors of the nicotinic acetylcholine receptor and the various glutamate r<.~ceptors. Analogues carrying photoaffinity labels, fluorine atoms for solid-state NMR studies of ligand/receptor interaction, and large head groups such as porphyrins and planar bulky aromatic rings (BIG analogues) for clarifying mode of entry and orientation of analogues in recep...
متن کاملPii: S0968-4328(99)00045-1
A scanning transmission electron microscope (STEM) is used to examine the structural and chemical quality of the interface between thin films of YBa2Cu3O72d (YBCO) and BaF2. The STEM images indicate that it is possible to grow a uniform thin film of BaF2 that is relatively free of gross defects via a thermal evaporation method on top of a YBCO thin film. The diffraction contrast results also su...
متن کاملPii: S0968-0896(98)00247-8
ÐThe theory of absolute reaction rates suggests that enzymes, like other catalysts, can enhance the rate of a reaction only to the extent that they bind the altered substrate in the transition state (S{) more tightly than they bind the substrate in the ground state (S). ES dissociation constants commonly fall in the physiological range, but recent kinetic studies indicate that formal ES{ dissoc...
متن کاملPii: S0968-0896(98)00211-9
ÐN-Benzoyloxy-2-thiopyridone (12) was shown to induce single-strand nicks in duplex DNA upon irradiation with visible light (l&350 nm). This ®nding led to the design of a series of compounds, in which an acridinyl nucleus was covalently linked to the N-benzoyloxy-2-thiopyridone unit. These conjugates (15, 16, 17 and 18) were synthesized and evaluated as novel DNA photocleaving reagents. Optimal...
متن کامل