Academia Sinica

Sloan-kettering Institute for Cancer Research

Memorial Sloan Kettering Cancer Center

National Health Research Institutes

Tsann-Long Su

Ting-Chao Chou

Kyoichi A Watanabe

Te-Chang Lee

Malcolm A Moore

Jang-Yang Chang

Che-Kun James Shen

Cheng-Wen Wu

Tai-Lin Chen

Yu-Chi Chou

Te-Chuang Lee

Jae-Hung Shieh

Jai-Tung Huang

Grazyna Ciszewska

Tiang-Chao Chou

Felicia Y-h Wu

Disclosed herein are novel bifunctional compounds and their uses for the treatment and/or prophylaxis of cancers. The bifunctional compound disclosed herein has the structure of formula (I), wherein, optionally substituted with one or more substituents independently selected from the group consisting of halo, alkyl, haloalkyl, alkenyl, C(O)H, OH, O(alkyl), O(CO)alkyl, O(aryl), aryl, and &#x2014;O(CH)N(R);

Substituted pyrrolo[2,1-a]phthalazines and benzo[g]pyrrolo[2,1-a]phthalazines for the treatment of cancer

Method of using ureidomustine (BO-1055), a water-soluble NDA cross-linking agent, in the treatment of a cancer, selected from the group consisting of various types of human leukemia [such as acute myeloid leukemia (ALL) and acute B Lymphoblastic leukemia (B-ALL)], lymphomas, small lung cell carcinoma (SCLC), sarcomas, and others.

Use of ureidomustine (BO-1055) in cancer treatment

Compounds, pharmaceutical compositions, and methods for treating anemia (&#x3b2;-thalassemia anemia or sickle cell anemia.

Methods and compositions for treating &#x3b2;-thalassemia and sickle cell disease

The present disclosure relates to new DNA-directed alkylating agents and water-soluble N-mustard agents with improved chemical stability and anti-tumor therapeutic efficacy.

Phenyl N-mustard linked to DNA-affinic molecules or water-soluble aryl rings, method and their use as cancer therapeutic agents

A pharmaceutical composition for treating cancer, in particular drug resistant cancer, comprising an effective amount of bifunctional alkylating agent, an effective amount of a DNA repair inhibitor, and a pharmaceutically acceptable carrier.

Method of treating cancer using combination of a bifunctional alkylating agent and DNA repair inhibitors

The present invention provides a series of 2,3-bis(hydroxymethyl)-4H-benzo[d]pyrrolo-[1,2-a]thiazoles and 1,2-bis(hydroxymethyl)indolizino[6,7-b]indole derivatives and their bis(alkylcarbamates) derivatives. These derivatives were designed as bi-functional DNA cross-linking agents. The in vitro cytotoxicity study of these compounds revealed that they exhibit significant anti-proliferative activity in inhibiting human lymphoblastic leukemia and various solid tumor cell growth. The compounds also exhibit therapeutic efficacy against human breast carcinoma and lung cancer in xenograft model. The compounds generally possess potent antitumor activity to kill various human solid tumors and have high potential for clinical applications.

Synthesis of 4H-benzo[D]pyrrolo[1,2-A]thiazoles and indolizino[6,7-b]indole derivatives and their use as antitumor therapeutic agents

The present disclosure relates to a series of bis(hydroxymethyl) and its bis(carbamate) of 8H-3a-azacyclopenta[a]indene-1-yl and 5,10-dihydropyrrolo-[1,2-b]isoquinolines derivatives (Formula I-Formula IV) as DNA di-alkylating agents. The preliminary antitumor studies indicated that compounds disclosed herein could exhibit potent cytotoxicity in vitro and antitumor therapeutic efficacy in human tumor xenografts and could have little or no cross-resistance to either Taxol or Vinblastine. The results demonstrated that compounds disclosed herein possess potent antitumor therapeutic efficacy and are expected to have potential for clinical applications.

Synthesis of 8H-3A-aza-cyclopenta [A ]indenes and 5,10-dihydropyrrolo[1,2-B]isoquinolines derivatives and their use as antitumor therapeutic agents

New aniline or phenol N-mustards linked to DNA-affinity carriers (such as 9-anilinoacridines, acridines and quinolines), aminobenzamides or aminophenol ethers by a urea, carbamic acid, carbanic acid ester, hydrazineurea, hydrazinecarbamic acid ester, phenoxyurea, phenoxycarbamic acid ester linkage with improved chemical stability and anti-tumor therapeutic efficacy are provided.

Aniline or phenol mustards linked to DNA-affinic molecules or water-soluble aromatic rings and their use as cancer therapeutic agents

This invention relates to 9-anilinoacridine compounds, and more particularly to their synthesis and their use in pharmaceutical compositions for treating diseases.

5-(9-acridinylamino)-toluidine compounds

The invention provides a compound of the following formula: ##STR1## wherein R.sup.1 is C.sub.1-6 alkyl; or phenyl;

Alkyl N-�3-(acridin-9-yl)amino-5-hydroxymethyl! phenylcarbamates

The present invention provides compounds having the structure: ##STR1## or having the structure: ##STR2## The present invention also provides a pharmaceutical compostion containing the compounds, methods of synthesizing the compounds, as well as methods of inhibiting growth of tumor cells and of treating a subject having a disease characterized by the proliferation of tumor cells.

Antitumor cyclopentnaphthoquinone and cyclopentanthraquinone derivatives

The present invention provides a compound having the structure: ##STR1## wherein R.sup.1 and R.sup.2 are independently the same or different and are hydrogen, an acetyl group; an acyl group having the formula --CO(CH.sub.2).sub.n COCH.sub.3, wherein n=1-3; --CO(CH.sub.2).sub.n COOM, wherein n=1-4 and M is hydrogen, Na or K; or --(CH.sub.2).sub.n COOR, wherein n=1-4 and R is hydrogen, Na, K or an alkyl group having 1 to 5 carbon atoms; a hydroxyalkyl group having the formula --(CH.sub.2).sub.n CH.sub.2 OH, wherein n=1-4; a halo alkyl group having the formula --(CH.sub.2).sub.n CH.sub.2 X, wherein n=1-4 and X is a chloro, bromo, or iodo group; a metal sulfonate (--SO.sub.3 M) wherein M is Na or K; a metal sulfinate (--SO.sub.2 M) wherein M is Na or K; a alkyl sulfonate (--SO.sub.3 R) wherein R is an alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, n-propyl or i-propyl; an alkylsulfonyl group (--SO.sub.2 R) wherein R is an alkyl group having 1 to 4 carbon atoms such as methyl, ethyl, n-propyl or i-propyl; a metal alkylsulfonate having the formula --(CH.sub.2).sub.n SO.sub.3 M wherein n=2-3 and M is Na or K; a metal alkylsulfate having the formula --(CH.sub.2).sub.n OSO.sub.3 M wherein n=2-3, and M is Na or K; or a .beta.-alanyl group. The present invention also provides a process for synthesizing the above-identified compound, intermediate compounds produced thereby, a pharmaceutical composition comprising the above compounds as well as a method for inhibiting growth of tumor cells using these compounds.

3-(9-acridinylamino)-5-hydroxymethylaniline derivatives as anticancer

The present invention provides a compound having the structure: ##STR1## The present invention also provides a method for synthesizing a compound having the above-identified structure as well as the intermediate compounds produced according to that method. The present invention further provides a pharmaceutical composition comprising the above compounds. Lastly, the present invention provides a method of inhibiting growth of tumor cells.

Multisubstituted 1-hydroxy-9-acridones with anticancer activity

This invention concerns compounds having the structure: ##STR1## wherein each of R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.2', R.sup.3', R.sup.4', and R.sup.5', is independently hydrogen (--H), or a hydroxyl (--OH), methoxy (--OMe), methyl (--Me), carboxaldehyde (--CHO) or phenylformazen (Ph--N.dbd.CH--) group. This invention also provides a novel process of synthesizing the compounds of the subject invention, including intermediate compounds useful in the process. The present invention also provides pharmaceutical compositions comprising a pharmaceutically effective amount of a compound according to the subject invention and a pharmaceutically acceptable carrier. Finally, the invention provides spermicidal methods and methods of killing or of retarding the proliferation of, cancer cells.

Growing community of inventors

Taipei, Taiwan

Tsann-Long Su