Pharma Mar, S.a.

Simon Munt

Ignacio Manzanares

Carmen Cuevas

Pilar Gallego

Alberto Rodriguez

Marta Perez

Valentin Martinez Barrasa

Ignacio Rodriguez

Valentin Martinez

Natividad Rodriguez

Roberto Menchaca

Maria Flores

Jonathan Charles Morris

Regan James Anderson

Andres Francesh

María Jesús Martin

Andrés Francesch

Maria Zarzuelo

Carolina Fernandez

Jose Luis Chicharro

Juan Jose Gonzalez

Felix Cuevas

Concepción Polanco

Carlos Del Pozo

José Luis Chicharro

Carolina Fernández

Modesto Remuiñan

Paloma Mandez

María Jesus Martin

Paloma Mendez

Modesto Remuiñán

Jose Luis Aceña

Javier Adrio

Maria Jesus Martin

Concepcion Polanco

Juan José Gonzalez

Derivatives of Et-743 or Et-770 or Et-729 are provided. The derivatives are of the general formula Ia.: wherein the substituent groups take various permitted meanings.

Antitumoral derivatives of ET-743

Antitumor compounds have the five membered fused ring ecteinascidin structure of the formula (XIV). The present compounds lack a 1,4-bridging group as found in the ecteinascidins. They have at the C-1 position a substituent selected from an optionally protected or derivatised aminomethylene group or an optionally protected or derivatised hydroxymethylene group. 

Antitumoral analogs of ET-743

Ecteinascidin compounds with a quinone ring for ring E are active as anti-cancer agents. Related processes and compounds are provided.

Synthesis of naturally occuring ecteinascidins and related compounds

Synthesis of naturally occurring ecteinascidins and related compounds

Variolin derivatives of formula (5) are provided, wherein the substituent groups defined by X, R, R, R, R, R, and Rare each independently selected from the group consisting of H, OH, OR', SH, SR&#x2032;, SOR&#x2032;, SOR&#x2032;, NO, NH, NHR&#x2032;, N(R&#x2032;), NHCOR&#x2032;, NHSOR&#x2032;, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)R&#x2032;, COH, COR&#x2032;, carboxyalkyl, C-Calkyl, C-Calkenyl, C-Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic; wherein each of the R&#x2032; groups is independently selected from the group consisting of H, OH, SH, NO, NH, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)CH, COH, COCH, C-Calkyl, C-Calkenyl, C-Calkynyl, aryl, aralkyl and heteroaromatic; wherein the pairs of groups of Rand R, Rand R, Rand R, Rand R, or Rand Rmay be joined into a carbocyclic or heterocyclic ring system.

Variolin derivatives and their use as antitumor agents

Derivatives of ecteinascidin 736 of general formula (I) wherein the groups R, R, R, Rand Rare each independently selected from the group consisting of H, OH, OR', SH, SR&#x2032;, SOR&#x2032;, SOR&#x2032;, C(&#x2550;O)R&#x2032;, C(&#x2550;O)OR&#x2032;, NO, NH, NHR&#x2032;, N(R&#x2032;), NHC(O)R&#x2032;, CN, halogen, &#x2550;O, substituted or unsubstituted C-Calkyl, substituted or unsubstituted C-Calkenyl, substituted or unsubstituted C-Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic; wherein X is independently selected of OR&#x2032;, CN, (&#x2550;O), or H; wherein each of the R&#x2032; groups is independently selected from the group consisting of H, OH, NO, NH, SH, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)CH, COH, substituted or unsubstituted C-Calkyl, substituted or unsubstituted C-Calkenyl, substituted or unsubstituted C-Calkynyl, substituted or unsubstituted aryl; wherein m is 0, 1 or 2; and wherein n is 0, 1, 2, 3, or 4, and their use as antitumoral agent. 

Ecteinascidin analogs for use as antitumour agents

Derivatives of Et-743 or Et-770 or Et-729 are provided. The derivatives are of the general formula (Ia) wherein the substituent groups take various permitted meanings. 

The invention relates to aplidine derivatives of the general formula: which are useful for the treatment of tumors.

Synthetic methods for aplidine and new antitumoral derivatives, methods of making and using them

Variolin derivatives of formula (5) are provided, wherein the substituent groups defined by X, R, R, R, R, Rand Rare each independently selected from the group consisting of H, OH, OR', SH, SR&#x2032;, SOR&#x2032;, SOR&#x2032;, NO, NH, NHR&#x2032;, N(R&#x2032;), NHCOR&#x2032;, NHSOR&#x2032;, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)R&#x2032;, COH, COR&#x2032;, carboxyalkyl, C-Calkyl, C-Calkenyl, C-Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic; wherein each of the R&#x2032; groups is independently selected from the group consisting of H, OH, SH, NO, NH, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)CH, COH, COCH, C-Calkyl, C-Calkenyl, C-Calkynyl, aryl, aralkyl and heteroaromatic; wherein the pairs of groups Rand R, Rand R, Rand R, Rand R, or Rand Rmay be joined into a carbocyclic or heterocyclic ring system. 

Processes are provided for preparing compounds with a fused ring structure of formula (XIV). Such products include ecteinascidins and have a spiroamine-1,4-bridge. The process involving forming a 1,4 bridge using a 1-labile, 10-hydroxy, 18-protected hydroxyl, di-6,8-en-5-one fused ring compound. After formation of the 1,4 brige, C-18 protection is removed before spiroamine introduction. 

Synthetic process for the manufacture of an ecteinaschidin compound

Antitumor compounds have the five membered fused ring ecteinascidin structure of the formula (XIV). The present compounds lack a 1,4-bridging group as found in the ecteinascidins. They have at the C-1 position a substituent selected from an optionally protected or derivatised aminomethylene group or an optionally protected or derivatised hydroxymethylene group 

Antitumour compounds have the five membered fused ring ecteinascidin structure of the formula (XIV). The present compounds lack a 1,4-bridging group as found in the ecteinascidins. They have at the C-1 position a substituent selected from an optionally protected or derivatised aminomethylene group or an optionally protected or derivatised hydroxymethylene group.

Antitumoral analogs of et-743

New spisulosine derivatives of use in treating tumors are of the formula (I) wherein: each X is the same or different, and represents H, OH, OR', SH, SR&#x2032;, SOR&#x2032;, SOR&#x2032;, NO, NH, NHR&#x2032;, N(R&#x2032;), CN, halogen, C(&#x2550;O)H, C(&#x2550;O)CH, COH, COCH, substituted or unsubstituted C&#x2013;Calkyl, substituted or unsubstituted C&#x2013;Calkenyl, substituted or unsubstituted C&#x2013;Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaromatic, or two groups X may together form &#x2550;O; Y is NR, OR, PR, SR, or halogen, wherein the number of substituents Ris selected to suit the valency and each Ris independently selected of H, OH, C(&#x2550;O)R&#x2032;, P(&#x2550;O)R&#x2032;R&#x2033;, substituted or unsubstituted C&#x2013;Calkyl, substituted or unsubstituted C&#x2013;Calkenyl, substituted or unsubstituted C&#x2013;Calkynyl, substituted or unsubstituted aryl, and wherein the dotted line indicates an optional double bond; each Z is the same different, and represents H, OH, OR&#x2032;, SH, SR&#x2032;, SOR&#x2032;, SOR&#x2032;, NO, NH, NHR&#x2032;, N(R&#x2032;), NHC(O)R&#x2032;, CN, halogen, C(&#x2550;O)H, C(&#x2550;O)CH, COH, COCH, substituted or unsubstituted C&#x2013;Calkyl, substituted or unsubstituted C&#x2013;Calkenyl, substituted or unsubstituted C&#x2013;Calkenyl, substituted or unsubstituted C&#x2013;Calkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaromatic, or two groups Z may together form &#x2550;O; z is 0 to 25; y is to 0 to 20; Ris H, C(&#x2550;O)R&#x2032;, P(&#x2550;O)R&#x2032;R&#x2033;, S(&#x2550;O)R&#x2032;R&#x2033;, S(&#x2550;O)R&#x2032;, substituted or unsubstituted C&#x2013;Calkyl, substituted or unsubstituted C&#x2013;CAlkenyl, substituted or unsubstituted C&#x2013;Calkynyl, substituted or unsubstituted aryl; Ris H, C(&#x2550;O)R&#x2032;, P(&#x2550;O)R&#x2032;R&#x2033;, S(&#x2550;O)R&#x2032;R&#x2033;, S(&#x2550;O)R&#x2032;, substituted or unsubstituted C&#x2013;Calkyl, substituted or unsubstituted C&#x2013;Calkenyl, substituted or unsubstituted C&#x2013;Calkynyl, substituted or unsubstituted aryl; each of the R&#x2032;, R&#x2033; groups is independently selected from the group consisting of H, OH, NO, NH, SH, CN, halogen, &#x2550;O, C(&#x2550;O)H, C(&#x2550;O)CH, COH, CO, substituted or unsubstituted C&#x2013;Calkyl, substituted or unsubstituted C&#x2013;Calkoxy, substituted or unsubstituted C&#x2013;Calkenyl, substituted or unsubstituted C&#x2013;Calkynl, substituted or unsubstituted aryl; there may be one or more unsaturations in the hydrocarbon backbone defined by the chain (II) and salts thereof; with the exception of a C&#x2013;C2-amino-3-hydroxyalkane or a C&#x2013;C2-amino-3-hydroxyalkene 

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Madrid, Spain

Simon Munt