Patent focus on cancer chemotherapeutics. IV Angiogenesis agents: April 2001 - August 2001

Connell, Richard D; Beebe, Jean S.

doi:10.1517/13543776.11.12.1919

Cited by 5 publications

(12 citation statements)

References 48 publications

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“…Within the single carbon bridge series, the C-3´´-and C-2´´-linked pyridyl analogs are both poor KDR inhibitors (IC 50 > 10 µM). Although increasing the chain length leads to a 4-fold loss in potency against Flt-1 for analog 31 compared with PTK 787 (27), it appears chain extension analogs may require a different pyridyl nitrogen position. For example, analog 32 [122] is a preferred compound in a follow up application (no specific data), and there is additional evidence within the closely related isoquinoline series discussed below (compare with compounds 40 and 41).…”

Section: -Cyanoquinolinesmentioning

confidence: 99%

“…Bayer further expanded the SAR at the C-2´´ position with the amide analog 33 [123] (no specific activity). The team at Novartis has published an extensive collection of in vivo pharmacology for PTK787 (27). As a class, the phthalazines appear to be orally well absorbed in the mouse [125].…”

Section: -Cyanoquinolinesmentioning

confidence: 99%

“…The newly formed small vessels are subsequently remodeled into mature vessels through the acquisition of a pericyte coating (via PDGF). Each of the steps in angiogenic signaling and vessel formation can be disrupted with small molecules [24][25][26][27]. In addition to specific target directed approaches, non specific 'vascular targeting' agents can be used to kill endothelial cells thereby inhibiting angiogenesis [28].…”

Section: Introductionmentioning

confidence: 99%

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Small Molecule Inhibitors of KDR (VEGFR-2) Kinase: An Overview of Structure Activity Relationships

Boyer¹

2002

CTMC

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The Kinase insert Domain containing Receptor (KDR), alternatively referred to as VEGFR-2, is a receptor for Vascular Endothelial Growth Factors (VEGFs) and functions as a key regulator of angiogenesis, the process by which new capillaries are created from preexisting blood vessels. The induction of angiogenesis, or the "angiogenic switch," is a critical step in tumor progression, and inhibitors of KDR have been demonstrated both to induce tumor regression and reduce metastatic potential in preclinical models. In the last few years, medicinal chemists have expanded the kinase selectivity profile of known inhibitor classes to include KDR, and also identified novel classes of KDR inhibitors. This review presents structure activity relationships (SAR) of small molecule inhibitors of KDR, with an emphasis on the pharmacophore elements of the scaffolds employed. Binding hypotheses based on X-ray crystallographic analyses will also be described. Additionally, the efficacy of representative compounds in in vitro and in vivo models of tumor progression and angiogenesis are discussed.

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Section: -Cyanoquinolinesmentioning

confidence: 99%

Section: -Cyanoquinolinesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Small Molecule Inhibitors of KDR (VEGFR-2) Kinase: An Overview of Structure Activity Relationships

Boyer¹

2002

CTMC

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“…The application focuses on two compounds, SU-5416 (7) and SU-6668 (8), which are explicitly cited in the claims of the application. A later application, relating to an intravenous formulation of SU-5416 and SU-6668, has also been filed by Pharmacia [131].…”

Section: Platelet-derived Growth Factor and The Plateletderived Growtmentioning

confidence: 99%

“…Like previous reviews on this topic [5][6][7][8], this paper seeks to summarise patent applications that relate to angiogenesis inhibitors as cancer therapeutics. However, this review focuses exclusively on the four main growth factor pathways involved with angiogenesis: angiopoietin, fibroblast growth factor (FGF), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF).…”

Section: Introductionmentioning

confidence: 99%

Patent focus on cancer chemotherapeutics V. Angiogenesis agents: September 2001 – August 2002

Connell

2002

Expert Opinion on Therapeutic Patents

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Kombinatorische Flüssigphasensynthese von Bibliotheken: auf der Suche nach Modulatoren für Protein‐Protein‐ und Protein‐DNA‐Wechselwirkungen in der zellulären Signaltransduktion

2003

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Hochdurchsatzsynthese und ‐screening von Verbindungsbibliotheken haben große Erwartungen für die Wirkstoffsuche geweckt. Für die Herstellung solcher Bibliotheken an der Festphase und in Lösung sind leistungsfähige Methoden entwickelt worden. Die Synthesestrategie wird schon lange nicht mehr nach allgemeinen Erwägungen ausgewählt, sondern mit Blick auf die spezielle Fragestellung. In diesem Aufsatz beschreiben wir Unterschiede zwischen den beiden Methoden, die bei der Entwicklung neuer Programme helfen sollen. Als Beispiel beschreiben wir unsere Versuche, mithilfe von Lösungstechniken Modulatoren für zelluläre Signale durch Beeinflussung von Protein‐Protein‐ oder Protein‐DNA‐Wechselwirkungen zu identifizieren. Das Vorurteil, niedermolekulare Substanzen seien für therapeutische Intervention an solchen Zielstrukturen ungeeignet, konnten wir beim Screening unserer Bibliotheken gegen eine repräsentative Auswahl extrazellulärer und intrazellulärer Targets widerlegen: Mithilfe zahlreicher Testmethoden identifizierten wir die ersten niedermolekularen Modulatoren für Protein‐Protein‐Wechselwirkungen und erarbeiteten ein allgemeines Verfahren für derartige Untersuchungen.

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Patent focus on cancer chemotherapeutics. IV Angiogenesis agents: April 2001 - August 2001

Cited by 5 publications

References 48 publications

Small Molecule Inhibitors of KDR (VEGFR-2) Kinase: An Overview of Structure Activity Relationships

Small Molecule Inhibitors of KDR (VEGFR-2) Kinase: An Overview of Structure Activity Relationships

Patent focus on cancer chemotherapeutics V. Angiogenesis agents: September 2001 – August 2002

Kombinatorische Flüssigphasensynthese von Bibliotheken: auf der Suche nach Modulatoren für Protein‐Protein‐ und Protein‐DNA‐Wechselwirkungen in der zellulären Signaltransduktion

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