Technion Research & Development Foundation Limited

Other

California Institute of Technology

Saltsman, Irina

Simkhovich, Liliya

Galili-nachshon, Nitsa

Gross, Zeev

Zeev Gross

Adi Haber

Harry B Gray

Michael Aviram

Joshua Palmer

Atif Mahammed

Avner Yayon

Bianca Fuhrman

Silvia Mandel

Itzchak Angel

Liliya Simkhovich

Nitsa Galili-Nachshon

Irina Saltsman

David Aviezer

Irena Saltsman

Raymond Coleman

Tamar Amit

Zoya Okun

Orit Bar-Am

Lana Kupershmidt

Moussa BH Youdim

Embodiments of the invention relate to methods of treatment a cardiovascular disease in a patient comprising administering an effective amount of a statin or a pharmaceutically acceptable salt thereof in combination with an effective amount of a transition metal complex of a corrole, an optically active isomer thereof or a pharmaceutically acceptable salt thereof. Further embodiments refer to pharmaceutical compositions comprising a statin and a corrole. Optionally, the corrole has a structure: wherein;M is a transition metal selected from the group consisting of Mn, Fe, Ru, Co, V, Cr, and Cu and R, R, R, X, X, XX; E, E, Eand Eare each defined as in the specification.

Combinations of corroles and statins

An embodiment of the invention provides a use of an effective amount of a transition metal complex of a corrole, an optically active isomer thereof, or a pharmaceutically acceptable salt thereof for treating a disease of the eye and/or the kidney in a subject suffering from diabetes. An embodiment of the invention further provides a use of a transition metal complex of a corrole, an optically active isomer thereof, or a pharmaceutically acceptable salt thereof for lowering serum glucose and serum triglyceride levels in a subject suffering from diabetes.

Method of treatment of disease

Metallocorrole complexes of third row transition metals (see Formula I below) may be used as therapeutic agents, catalysts, components of oxygen detectors, and components of light emitting diodes. In particular, metallocorrole complexes of third row transition metals may be used as improved photosenitizers in photodynamic therapy; as improved catalysts in aziridination, epoxidation, and water splitting reactions; as improved in vivo imaging agents; and as improved components in the emissive layer of OLEDs. Due to their strongly sigma-donating nature, corroles are able to stabilize third row transition metals in high oxidation states. Third row transition metals are significantly more electropositive than their first and second row counterparts and may therefore act as improved catalysts. In addition, the high spin-orbit coupling constants of third row transition metals may lead to easier singlet-triplet inter-system crossing in the excited state, which in turn may allow for long-wavelength phosphorescence that is desirable for many applications. 

Metallocorroles

Transition metal complexes of amphiphilic/bipolar corroles, optically active isomers or pharmaceutically acceptable salts thereof are useful for prevention of a cardiovascular disease or disorder in a subject susceptible to develop such a cardiovascular disease or disorder.

Transition metal complexes of corroles for preventing cardiovascular diseases or disorders

Corroles of formula I, wherein Ar is aryl or heteroaryl; M is absent or is a metal selected from Al, Ga, Co, Mn, Fe, Ru, Sn, Cr or Rh; E, Eand E, the same or different, each is H, SOCl, SOH, SONRR, COH, COR, COC, CONRR, CHO or NO, R is alkyl or aryl, and Rand R, the same or different, each is H, alkyl, aryl or together with the N atom to which they are attached form a saturated 5-6 membered ring optionally containing a further heteroatom selected from O, S and N; and Eis H or CHO; or Eand Eare H and Eand Eare each SO, both SOgroups being linked by a bridge RN(R)-phenyl-(R)NR, wherein Ris H, alkyl, phenyl or aralkyl, and Ris alkylene; and provided that at least one of E, E, Eand Eis not H, are provided. The corroles can be used for tumor detection and treatment, in photovoltaic devices, as catalysts and as intermediates.

Method for the preparation of selectively-substituted corroles and new substituted corroles

Tertrapyrrolic macrocycles selected from 5,10,15,20-tetraaryl-porphyrins and 5,10,15-triaryl-corrloes, wherein said aryl radical is a carboaryl, a heteroaryl or a mixed carboaryl-heteroaryl radical and at least two of said aryl radicals are positively charged, inhibit growth factor (e.g. bFGF, VEGF) receptor tyrosine kinase activity, and are useful for inhibition of cell proliferation mediated by growth factor receptor tyrosine kinase activity for example for inhibition of angiogenesis, or vascular smooth muscle cell proliferation in disorders including atherosclerosis, hyperthrophic heart failure and postsurfical restenosis, and of cell proliferation and migration in the treatment of primary tumors and metastasis. Some of the 5,10,15,20-tetraaryl-prophyrins are novel compounds.

Pharmaceutical compositions comprising porphyrins and some novel porphyrin derivatives

A new process for the preparation of corroles, having the structure of formula I below relies on a solvent-free condensation of an aldehyde with a pyrrole. Further disclosed are several new corroles, salts, optically active isomers and complexes thereof synthesized using the process.

Process for the preparation of corroles and several such new compounds, including chiral derivatives, and the use thereof

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Petach Tikva, Israel

Zeev Gross