Functionalized thieno-indole derivatives for the treatment of cancer

US9561290B2 · kind B2 · utility

Assignee

• NERVIANO MEDICAL SCIENCES S.R.L. · IT

Inventors

• Italo Beria · Nerviano, IT
• Michele Caruso · Milano, IT
• Vittoria Lupi · Milano, IT
• Paolo Orsini · Legnano, IT
• Matteo Salsa · Novara, IT

Key dates

• Filing date: Mar 28, 2013
• Grant date: Feb 7, 2017
• Expiry date: Mar 28, 2033

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D495/04
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The invention relates to new functionalized thieno-indole derivatives of formula (I) or (II) which have cytotoxic activity and are useful in treating diseases such as cancer and cellular proliferation disorders. The invention also relates to the use of these functionalized thieno-indole derivatives in the preparation of conjugates. Formula (I) or (II) wherein R1 and R2 taken together form a group (D) or (G): wherein R5 is hydrogen or C1-C4 alkyl; R3 and R4 are independently hydrogen, C1-C4 alkyl or C1-C4 hydroxyalkyl; n is 0, 1 or 2; each of X is independently —O—, —S— or —NR4—; each of Y is independently —CH═ or —N═; R7 and R8 are independently hydrogen, halogen, hydroxy, C1-C4 alkoxy, cyano, —NHCOOR3, —C(NH)NH2 or —NR3R4; A is —O—, —NH— or —CO—; L is null or a conditionally-cleavable moiety; W is null or a self-immolative moiety comprising one or more self-immolative groups; Z is null or a peptidic, non peptidic or hybrid peptidic and non peptidic linker; RM is null or a reactive moiety; R6 is a leaving group; A1 is null or A; L1 is hydrogen or L.