64 research outputs found
Synthetic MMP Inhibitors: Slow-Binding Behaviour of Enantioselective N-O-Sulphonamido Based Inhibitors Directed to Specific Matrixins
No full textDiagnostic Agents Selective agains Metalloproteinases
No full textThe invention relates to aryl-sulfonamido compds. endowed with affinity against metallo proteases MMP, having formula
(I) below wherein R, R1, R2, R3, G and n have the meanings reported in the specification, properly labeled with
diagnostic imaging moieties or even radiotherapeutic moieties. The invention also refers to the process for their prepn.,
to pharmaceutical compns. comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents.
The invention relates to arylsulfonamido compds. of formula I, which endowed with affinity against metalloproteases
MMP and are useful as diagnostic imaging agents. The invention also refers to the process for their prepn., to
pharmaceutical compns. comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents.
Compds. of formula I wherein R is -Ar-X-Ar1; Ar is (un)substituted (hetero)arylene and (un)substituted (hetero)aryl; Ar1 is
(un)substituted (hetero)aryl and H; X is a single bond, (un)branched C1-4 alkylene, O, S, SO2, CO, NH and derivs.,
NHCO and derivs., and CONH and derivs.; R1 is H, OH, Ra and ORa; Ra is (un)branched C1-4 alkyl, C2-4 alkenyl and -
(CH2)0-4-Z-(CH2)0-4-W; Z is a single bond, O, NH and derivs., NHCO and derivs., and CONH and derivs.; W is
(un)substituted Ph and (un)substituted 5- to 6-membered heterocycle; R2 and R3 are independently H, (un)substituted
(un)branched C1-4 alkyl and a zinc binding group; G is (un)branched C1-6 alkyl, (hetero)aryl, arylalkyl and -(CH2)1-6-
NH2 and derivs.; and their pharmaceutically acceptable salts thereof, are claimed. Example compd. II·2CF3COOH was
prepd. via hydroxyamidation of the corresponding acid with O-(tert-butyldimethylsilyl)hydroxylamine. All the invention
compds. were evaluated for their metalloprotease inhibitory activity. From the assay, it was detd. that II exhibited the
IC50 value of 0.3 ± 0.03 nM and 0.2 ± 0.01 nM against MMP2 and MMP13, resp
Arylsulfonamido compounds as metalloprotease inhibitors and their preparation, pharmaceutical compositions and use as diagnostic as well as radiotherapeutic agents
No full textThe invention relates to aryl-sulphonamido compounds endowed with affinity against metallo proteases MMP, having formula (I) below wherein R, R 1 , R 2 , R 3 , G and n have the meanings reported in the specification, properly labelled with diagnostic imaging moieties or even radiotherapeutic moieties. The invention also refers to the process for their preparation, to pharmaceutical compositions comprising them and to their use as diagnostic imaging agents or radiotherapeutic agents
Synthetic MMP Inhibitors: Slow-Binding Behaviour of Enantioselective N-O-Sulfonamido Based Inhibitors Directed to Specific Matrixins
No full textThe kinetic behavior of some newly synthesized hydroxamate inhibitors on the matrixins MMP2 and MMP13 was
evaluated. Our enantiomeric N-O-alkylsulfonamido-based MMP inhibitors (R)-EN73 and (S)-EN73, which show IC50
values in the nanomolar range on these matrixins, were found to display slow-binding kinetics. On the contrary, their
achiral analogs devoid of the P1 substituent, such as CC27, or other model inhibitors bearing different substituents in P2'
as the N-alkylsulfonamido-based SM3 or the N-H sulfonamido-based FO8, displayed a kinetic behavior consistent with a
rapid equil. interaction with these enzymes. This behavior, however, was not obsd. when the same enantiomeric
compds. were tested on a different matrixin, e.g., MMP-1, that shows a far higher IC50 value for these inhibitors.
Considering shape and size differences of the S1' pocket of these matrixins, we carried on this kinetic characterization
also on P1' small arom. substituted inhibitors belonging to these sulfonylated ligands. An enlarged and compared anal.
regarding the potency and selectivity of these inhibitors, against some target and antitarget MMPs involved in cancer and
arthritic diseases, was developed
From taxuspine X to structurally simplified taxanes with remarkable P-Glycoprotein inhibitory activity
No full textThree simplified “non-natural” natural taxanes, related to taxuspine X, were synthetized and assayed as P-glycoprotein (P-gp) inhibitors. One of them (6) proved to be a very efficient P-gp inhibitor with an IC50 = 7.2 × 10−6 M. In addition, to rationalize biological data, a pharmacophoric model was built through a ligand-based approach. This model represents the first example of a pharmacophore, which describes interactions of taxanes with P-gp
Stereoselective synthesis of advanced intermediates en route to Taxuspine U and X: a study of macrocyclization via ring closing metathesis to highly constrained twelve-membered rings
No full textThe stereoselective synthesis of an advanced intermediate of Taxuspine U and X has been accomplished using a ring closing metathesis strategy. The feasibility of ring closing metathesis in synthesizing highly constrained and functionalized macrocycles has been demonstrated provided the appropriate substrate structure and substitution pattern are chosen. © 2006 Elsevier Ltd. All rights reserved
Duties of so-called quoted joint stock companies
No full textDuties of so-called quoted joint stock companies Thesis author: Mgr. Marek Novotný Thesis supervisor: prof. JUDr. Stanislava Černá, CSc. This thesis is concerned with the regulation of duties of quoted joint stock companies (especially the duty of information) and its various institutes. The purpose of this thesis is to describe the legislation in this area of law and its development, with emphasis on the transposition of European legislation, and subject them to critical evaluation. In the first chapter the theoretical framework is defined by describing key legal concepts (the term "quoted joint stock company", "regulated markets") and the development of the most important legal regulation in this area - Act No. 256/2004 Coll., on Business Activities on the Capital Market. The second chapter is devoted to regulated markets and subject information duty. The third chapter deals with the admission of a security to trading on a regulated market and associated initial information duty of joint stock company, which is willing to become quoted. I describe mainly the prospectus and its essential elements. In the fourth chapter I analyze in detail the different types of regular (periodic) information duties, which are the annual report, semi-annual report and interim report. The following fifth chapter is..
Trust fund in Business Relations
No full textTrust Fund in Business Relations Author: Milan Sýkora Supervisor: prof. JUDr. Stanislava Černá, CSc. This diploma thesis deals with transplantation of trusts into the Czech Civil Code in the form of "svěřenský fond" (fiduciary fund) and with possibilities of this instrument in the world of commerce. The essential question is whether svěřenský fond is capable of replacing Anglo-Saxon trust in the following standard financial transactions: (i) syndicated loans, (ii) issues of bonds, (iii) subordination, (iv) securitization and (v) collective investment. In total, this thesis comprises of seven chapters, including the Introduction and the Conclusion. After an introduction, uncommonly, a prologue follows. This Prologue outlines a new, unusual instrument of the Czech law - svěřenský fond. It refers to the particular legislation and outlines questions that arise with this recently transplanted device. The third chapter defines trust using comparative law and deals with its historical development both on the British Islands and in the civil and mixed jurisdictions. The second subchapter argues that the so-called obstacles of trust reception into civil law are not based on solid arguments. Further, I describe experience of trust reception in selected civil law and mixed jurisdictions. In the fourth..
Contract for the sale of enterprise
No full textTHESIS TITLE OF THESIS: Contract for the sale of enterprise AUTHOR: Mgr. Vladimír Trnavský DEPARTMENT: Commercial law department ADVISOR: Prof. JUDr. Stanislava Černá, Csc. The theme of the thesis is "contract for the sale of enterprise". The theme itself is very acctented within the frame of legal practice. The main goal of this work is to outline the development genesis of the legal term enterprise since the time of classical roman law period to the contemporary legal regulation and subsequently, after defining the fundamental charts of the contract for the sale of enterprise, to answer specific questions resulting from the contract for the sale of enterprise in specific situations, i.e. the question of joint ownership of enterprise, legal frame of joint ownership relating to particular components of the enterprise, question of plurality on one or both parties to a contract a its consequences in commercial and labour law. The assess of creation of active and passive solidarity and its impact on the sale of enterprise i salso emphasized. Among the thesis goals also belongs the finding the answer on query of specific property values (for example the shares in cooperative society) with respect to the person who acquires the entrerprise and with respect to possible plurality of buyers. The goal of..
Design, synthesis, biological evaluation and NMR studies of a new series of arylsulfones as selective and potent MMP-12 inhibitors
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