Telomerase inhibitors

Details Telomerase inhibitors Telomerase inhibitors

1995-09-29

1998-06-23

Raymond, Richard L.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

514335, 514336, 514337, 514340, 514342, 514344, 514345, 514350, 514352, 546261, 546274, 546277, 546280, 546284, 546288, 546298, 546301, 546310, 546312, A61K 3144, C07D21364, C07D213643

Patent

active

057706131

ABSTRACT:
Methods and compositions for treating cancer and other diseases in which inhibition of telomerase activity can ameliorate disease symptoms or prevent or treat the disease relate to compounds that are derivatives of pyridine aldehydes, thioaldehyde, acetals, or thioacetals. Such compounds are characterized by the following structure: ##STR1## X.sub.1 is selected from the group consisting of oxygen, sulfur, sulfone, sulfinyl, and --NR-- where R is hydrogen, alkyl, aryl, and aralkyl. R.sub.1 is --Y.sub.n R.sub.6, in which n is an integer between 0 and 10 and each Y.sub.n for n greater than 0 independently is methylene, methine, or quarternary carbon. R.sub.6, for any value of n (i.e., n is zero or non-zero), is alkyl, aryl, heterocycle, heteroaryl, aralkyl, heteroaralkyl, alkylcarbonyl, arylcarbonyl, heteroarylcarbonyl, heteroaralkylcarbonyl, aralkylcarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aldehyde, sulfo, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, and arylsulfonyl. R.sub.6 can also be a linker L selected from the group consisting of alkyl, aryl, aralkyl, heterocycle, and heterocyclealkyl, to which linker between 1 and 3 additional compounds having the structure shown as Compound I above are attached to form thereby homogeneous or heterogeneous poly pyridine aldehydes, acetals, or thioacetals as described in greater detail below. R.sub.2 is hydrogen, alkyl, aryl, hydroxyl, alkoxyl, aryloxyl, halogen, cyano, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, alkylcarbonyloxy, arylcarbonyloxy, aldehyde, sulfo, alkylsulfinyl, arylsulfinyl, alkylsulfonyl, or arylsulfonyl. R.sub.3 and R.sub.4 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, aryloxyl, alkoxyl, lower alkyl, aryl, heteroaryl, aralkyl, cyano, carboxyl, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, heteroaralkyl, nitro, amino, alkylamino, arylamino, dialkylamino, diarylamino, and arylalkylamino. Finally, R.sub.5 is selected from the group consisting of bis(alkoxy)methyl, bis(alkylthio)methyl, and --HC.dbd.X.sub.2, where X.sub.2 is oxygen or sulfur.

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