Geron Corporation

Sutro Biopharma, Inc.

Adam Antoni Galan

Federico C Gaeta

Elaine C Stracker

Ryan Stafford

Gang Yin

Michael R Kozlowski

Alice Yam

Xiaofan Li

Cristina Abrahams

Krishna Bajjuri

Venita De Almeida

Karen R Prowse

Andreas Maderna

Patricia A Peterli-Roth

Willy Solis

Provided herein are compounds, trifunctional antibody products thereof, and methods and pharmaceutical compositions for use in treatment of inflammatory and/or proliferative diseases.

Immunomodulator antibody drug conjugates and uses thereof

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 characterized by the following structure: ##STR1## and their pharmaceutically acceptable salts. Y is selected from the group consisting of oxygen, sulfur, sulfonyl, sulfinyl, and --NR.sub.7 --. R.sub.1 is --TR.sub.8, where T is --C(X.sub.1)-- or --SO.sub.2 --, and R.sub.8 is selected from the group consisting of --OR.sub.9, --NHNHSO.sub.2 R.sub.9, --NHNHC(X.sub.2)OR.sub.9, --NR.sub.9 R.sub.10, --NHNHC(X.sub.2)NR.sub.9 R.sub.10, --NHCR.sub.9 R.sub.10 C(X.sub.2)NR.sub.11 R.sub.12, --NHC(X.sub.2)NR.sub.9 R.sub.10, and the piperazinyl moiety shown below: ##STR2## where n is 0 or 1, and Q.sub.n, for n=1, is --SO.sub.2 --, --C(X.sub.2)-- or --C(X.sub.2)NR.sub.10 --. R.sub.2 -R.sub.6 are selected independently from the group consisting of hydrogen, alkyl, aryl, hydroxyl, alkoxyl, aryloxyl, aralkoxyl, halogen, cyano, nitro, alkylcarbamido, arylcarbamido, dialkylcarbamido, diarylcarbamido, alkylarylcarbamido, alkylthiocarbamido, arylthiocarbamido, dialkylthiocarbamido, diarylthiocarbamido, alkylarylthiocarbamido, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonylamido, arylsulfonylamido, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, and arylsulfinyl. X.sub.1 and X.sub.2 are selected independently from the group consisting of oxygen, and sulfur. R.sub.7 -R.sub.12 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heterocycle, and heterocyclealkyl.

Telomerase inhibitors

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 pyrido�b!thiophenes, pyrido�b!furans, pyridine ethers or pyridine thioethers. Such compounds are characterized by the following structure: ##STR1## X.sub.3 is oxygen or sulfur; and the double dashed lines between X.sub.4 and X.sub.5 indicate an optional double bond, which, when present, forms a fused, bicyclic pyrido�b!furan or pyrido�b!thiophene ring system, depending upon whether X.sub.3 is oxygen or sulfur, respectively. When the double bond is not present, the compound is a monocyclic pyridine ether or thioether, again depending upon whether X.sub.3 is oxygen or sulfur. X.sub.4 is --CH.sub.2 R.sub.21 or --CR.sub.21 --, where R.sub.21 is selected from the group consisting of aryl, heteroaryl, aralkyl, heteroaralkyl, alkylcarbonyl, arylcarbonyl, heteroalkylcarbonyl, heteroaralkylcarbonyl, aralkylcarbonyl, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylarninocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl and arylsulfonyl; and X.sub.5 is hydrogen, alkyl, hydroxyl, alkoxyl, aryloxyl, halogen, cyano, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonyl, arylsulfonyl or --CR.sub.22 -- where R.sub.22 is selected from the group consisting of hydrogen, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, dialkylaminocarbonyl, diarylaminocarbonyl, arylalkylaminocarbonyl, hydroxyl, halogen, cyano, carboxyl, alkoxycarbonyl and aryloxycarbonyl. When X.sub.4 is --CR.sub.21 --, X.sub.5 is --CR.sub.22 --, and X.sub.4 and X.sub.5 are joined by the above-mentioned double bond, to form thereby a fused, bicyclic pyrido�b!thiophene (X.sub.3 is sulfur) or pyrido�b!furan (X.sub.3 is oxygen) ring system. When X.sub.4 is --CH.sub.2 R.sub.21, X.sub.5 is not --CR.sub.22 --, thereby forming a pyridine ether (X.sub.3 is oxygen) or thioether (X.sub.3 is sulfur). R.sub.18 and R.sub.19 are selected independently from the group consisting of hydrogen, halogen, hydroxy, aryloxy, alkoxy, lower alkyl, aryl, heteroaryl, aralkyl and heteroaralkyl. R.sub.20 is selected from the group consisting of alkoxymethyl, dialkoxymethyl, arylalkylaminomethyl, arylaminomethyl, alkylaminomethyl, aminomethyl, diarylaminomethyl, dialkylaminomethyl, hydroximinyl, iminyl, aldehyde, alkylcarbonyl, arylcarbonyl, alkyliminyl, aryliminyl, aralkyliminyl, alkoximinyl, aryloximinyl, heterocycleimninyl, alkoxycarbonyl, aryloxycarbonyl, carboxyl, alkene, --HC.dbd.NNHR.sub.23 where R.sub.23 is selected from the group consisting of hydrogen, alkyl, aryl, aralkyl, heterocycle, heterocyclealkyl, and --C(X.sub.6)NHR.sub.24 where X.sub.6 is oxygen or sulfur and R.sub.24 is selected from the group consisting of hydrogen, aryl, arylsulfonyl, aralkyl, heterocycle and heterocyclealkyl.

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 benzo�b!thiophenes. Such compounds are characterized by the following structure: ##STR1## In this compound, R.sub.1 is selected from the group consisting of --OR.sub.7, --NR.sub.8 R.sub.9, --NHNR.sub.10 R.sub.11, --NHNHC(X.sub.2)NHR.sub.12, --NHSO.sub.2 NR.sub.8 R.sub.9, --NHNHC(O)R.sub.12, --NHNHSO.sub.2 R.sub.12 and --NHC(O)NR.sub.8 R.sub.9. R.sub.7 -R.sub.12 are selected independently from the group consisting of hydrogen, alkyl, aryl, aralkyl, heteroaryl and heteroaralkyl. X.sub.1 and X.sub.2 are selected independently from the group consisting of oxygen and sulfur. R.sub.2 is hydrogen or halogen. R.sub.3 -R.sub.6 are selected independently from the group consisting of hydrogen, halogen, hydroxyl, --NR.sub.8 R.sub.9, nitro, cyano, alkoxyl, lower alkyl, aryl and aryloxyl.

Telomerase Inhibitors

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Richmond, CA, United States of America

Adam Antoni Galan