Pharma Mar, S.a.

Instituto Biomar, S.a.

Carmen Cuevas

Ignacio Manzanares

Simon Munt

Pilar Gallego

Marta Perez

Alberto Rodriguez

Valentin Martinez Barrasa

Maria Zarzuelo

Natividad Rodriguez

Roberto Menchaca

Ignacio Rodriguez

Valentin Martinez

Maria Flores

Andres Francesh

Jose Luis Chicharro

Carolina Fernandez

Regan James Anderson

Jonathan Charles Morris

María Jesús Martin

Felix Cuevas

Concepción Polanco

Carlos Del Pozo

Juan Jose Gonzalez

Andrés Francesch

José Luis Chicharro

Carolina Fernández

Librada Maria Cañedo

Modesto Remuiñan

Fernando De La Calle

Paco Romero

Maria Jesus Martin

Javier Adrio

Jose Luis Aceña

Modesto Remuiñán

Paloma Mendez

María Jesus Martin

José Fernando Reyes

Paloma Mandez

Leyre Malet

Fernando De Calle

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

Methods are provided for preparing a compound with a fused ring structure of formula (XIV) which comprises one or more reactions starting from a 21-cyano compound of formula (XVI) where typically; Ris an amidomethylene group or an acyloxymethylene group; Rand Rare independently chosen from &#x2014;H, &#x2014;OH or &#x2014;OCOCHOH, or Rand Rare both keto and the ring A is a p-benzoquinone ring; Rand Rare both &#x2014;H ozone is &#x2014;H and the other is &#x2014;OH, &#x2014;OCHor &#x2014;OCHCH, or Rand Rtogether form a keto group; and Rand Rare independently chosen from &#x2014;H or &#x2014;OH, or Rand Rare both keto and the ring A is a p-benzoquinone ring. In modified starting materials, the 21-cyano group can be replaced by other groups introduced using nucleophilic reagents. 

Hemisynthetic method and new compounds

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. 

Compounds of general formula (I) wherein R, R, Rare as defined and Rgroups are each independently selected from NR, O and S; are of use in treatment of cancers. 

Cytotoxic depsipeptides

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 

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Madrid, Spain

Carmen Cuevas