Targeted drug delivery via phosphonate derivatives

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai

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514 49, 514 50, 514885, 536 64, 536 171, 536 175, 536 187, 552502, 558 70, A61K 3100

Patent

active

051770644

ABSTRACT:
The invention provides compounds of the formula ##STR1## or a pharmaceutically acceptable salt thereof, wherein [D] is the residue of a drug having a reactive functional group, said functional group being attached, directly or through a bridging group, via an oxygen-phosphorus bond to the phosphorus atom of the ##STR2## moiety; R.sub.1 is C.sub.1 -C.sub.8 alkyl, C.sub.6 -C.sub.10 aryl or C.sub.7 -C.sub.12 aralkyl; R.sub.2 is hydrogen, C.sub.1 -C.sub.8 alkyl, C.sub.6 -C.sub.10 aryl, C.sub.4 -C.sub.9 heteroaryl, C.sub.3 -C.sub.7 cycloalkyl, C.sub.3 -C.sub.7 cycloheteroalkyl or C.sub.7 -C.sub.12 aralkyl; and R.sub.3 is selected from the group consisting of C.sub.1 -C.sub.8 alkyl; C.sub.2 -C.sub.8 alkenyl having one or two double bonds; (C.sub.3 -C.sub.7 cycloalkyl)--C.sub.r H.sub.2r --wherein r is zero, one, two or three, the cycloalkyl portion being unsubstituted or bearing 1 or 2 C.sub.1 -C.sub.4 alkyl substituents on the ring portion; (C.sub.6 -C.sub.10 aryloxy)C.sub.1 -C.sub.8 alkyl; 2--, 3-- or 4-- pyridyl; and phenyl-C.sub.r H.sub.2r -- wherein r is zero, one, two or three and phenyl is unsubstituted, or is substituted by 1 to 3 alkyl each having 1 to 4 carbon atoms, alkoxy having 1 to 4 carbon atoms, halo, trifluoromethyl, dialkylamino having 2 to 8 carbon atoms or alkanoylamino having 2 to 6 carbon atoms. The compounds are adapted for targeted drug delivery, especially to the brain.

REFERENCES:
patent: 4540564 (1985-09-01), Bodor
patent: 4816570 (1989-03-01), Farquhar
patent: 4968788 (1990-11-01), Farquar
Farquhar et al., J. Pharm. Sci., vol. 72, No. 3, Mar. 1983, 324-325.
Srivastva et al, Bioorganic Chemistry 12 (1984), 118-129.
Prisbe et al, J. Med. Chem., 1986, 29, 671-675.
Mitsuya et al, Science, vol. 249, Sep. 28, 1990, 1533-1543.

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