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BENZIMIDAZOLYL-METHYL UREA DERIVATIVES AS ALX RECEPTOR AGONISTS

The present invention relates to benzimidazolyl-methyl urea derivatives of formula (I), wherein n, D, E, R1, R2, R3, R4, R6, R7, R8 and R9 are as defined in the description, their preparation and their use as pharmaceutically active compounds.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Design of more potent antagonists of the antidiuretic responses to arginine-vasopressin

As part of a program aimed at designing more potent and selective antagonists of the antidiuretic responses to arginine-vasopressin (AVP), the authors substituted O-alkyl-D-tyrosine (where alkyl=methyl, ethyl, isopropyl, or n-propyl) at position 2 in our eight previously reported O-alkyl-L-tyrosine antagonists of antidiuretic and vasopressor responses to AVP. The authors also substituted D-tyrosine for L-tyrosine in two vasopressor antagonists with weak antidiuretic agonistic activity, [1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid),4-valine,8-D-arginine]vasopressin [d(CH2)5VDAVP] and its L-arginine isomer [d(CH2)5VAVP]. The ten analogues, synthesized by the solid-phase method, are as follows: 1) d(CH2)5-D-Tyr(Me)VDAVP; 2) d(CH2)5-D-Tyr(Et)VDAVP; 3) d(CH2)5-D-Tyr(i-Pr)VDAVP; 4) d(CH2)5-D-Tyr(n-Pr)VDAVP; 5) d(CH2)5-D-Tyr(Me)VAVP; 6) d(CH2)5-D-Tyr(Et)VAVP; 7) d(CH2)5-D-Tyr(n-Pr)VAVP; 8) d(CH2)5-D-Tyr(i-Pr)VAVP; 9) d(CH2)5-D-TyrVDAVP; 10) d(CH2)5-D-TyrVAVP. These analogues were tested for agonistic and antagonistic activities in rat antidiuretic and rat vasopressor systems. All ten D-tyrosine analogues possess transient weak antidiuretic activities (0.004-0.05 U/mg). Subsequent doses of AVP are reversibly antagonized for 1-3 h, depending on the dose of the antagonist. They exhibit the following antidiuretic pA2 values: 1) 7.19±0.11; 2) 7.59±0.04; 3) 7.51±0.06; 4) 7.60±0.05; 5) 7.77±0.07; 6) 7.81±0.07; 7) 7.66±0.11; 8) 7.61±0.06; 9) 7.03±0.05; 10) 7.51±0.08. They are all effective antagonists of vasopressor responses to AVP. Analogues 1-8 are two to ten times more potent than their respective O-alkyl-L-tyrosine isomers as antidiuretic antagonists. Since the vasopressor potencies of the O-alkyl-L-tyrosine analogues have either diminished or remained virtually unchanged, these analogues exhibit a selective increase in their antiantidiuretic/antivasopressor ratios with respect to their respective O-alkyl-L-tyrosine analogues. The finding that the substitution of an unalkylated D-tyrosine for L-tyrosine in d(CH2)5VDAVP and d(CH2)5VAVP converts these weak antidiuretic agonists into potent antagonists of antidiuretic responses to AVP is highly significant, especially in view of the relative ease of synthesis and much higher yields of unalkylated vs. alkylated tyrosine analogues. These ten new analogues are potentially useful as pharmacological tools and as therapeutic agents. The findings presented here have also obvious potential for the design of even more potent and selective antidiuretic antagonists.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

A new application about C20H13N3O2

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Discovery and optimization of a novel series of GPR142 agonists for the treatment of type 2 diabetes mellitus

The discovery and initial optimization of a series of phenylalanine based agonists for GPR142 is described. The structure-activity-relationship around the major areas of the molecule was explored to give agonists 90 times more potent than the initial HTS hit in a human GPR142 inositol phosphate accumulation assay. Removal of CYP inhibition by exploration of the pyridine A-ring is also described.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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NOVEL PHTHALAZINONE-PYRROLOPYRIMIDINECARBOXAMIDE DERIVATIVES

The compounds of formula (1), in which R1, R7, R8, R9, R10, R17, R18, R19, R20 and m have the meanings as given in the description, are novel effective inhibitors of type 4 and 5 phosphodiesterase.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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alpha,gamma-Cyclic peptide ensembles with a hydroxylated cavity

Here we describe a self-assembling alpha,gamma-cyclic tetrapeptide that contains the 4-amino-3-hydroxytetrahydrofuran-2-carboxylic acid, in which the hydroxy group is pointing towards the inner cavity of the resulting dimers.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

Archives for Chemistry Experiments of C20H13N3O2

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A concise synthesis of the cytotoxic depsipeptide arenastatin A

Arenastatin A (1, cryptophycin 24) was synthesized by convergence of hydroxy ester 16 with amino acid derivative 27; two independent and highly efficient routes to 16 are disclosed.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Tuftsin derivatives

Linear or cyclic tetra peptide derivatives of tuftsin which activate immunocompetent cells, i.e., macrophages and polymorphonuclear leukocyte, provide a host-mediated inhibition of the growth of tumors, provide protective effects for infectious diseases such as viral, bacterial and fungal diseases, and exhibit therapeutic effects on autoimmune diseases such as lupus erythematosus, rheumatoid and the like, and therefore, are useful for production of pharmaceutical preparations for the treatment of these diseases.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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A diastereoselective construction of pyrazinoisoquinoline skeletons via tandem cyclization of phenylalanine derivatives: A facile synthesis of optically active pyrazinoisoquinolines

A facile and stereocontrolled construction of optically active pyrazinoisoquinoline skeletons based on tandem cyclization of enantiopure phenylalanine derivatives was examined. The reaction provided optically active 6,11b-trans pyrazinoisoquinoline ring systems in excellent diastereoselectivity, and this method was applicable to the cyclization of phenylalanine derivatives with diverse substituents.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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HISTONE DEACETYLASE INHIBITOR AND PROCESS FOR PRODUCING THE SAME

HDAC inhibitors represented by formula (1) show strong inhibitory activity against various subtypes of HDACs. The compounds of the present invention find utility as pharmaceutical agents for treating or preventing diseases associated with HDAC 1, 4, and 6. The methods for producing the compounds of the present invention enable easy and simple synthesis of various types of these compounds, and are expected to contribute to the development of HDAC inhibitors having novel properties and the like.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Heterocyclic derivatives and their use as antithrombotic agents

The present invention relates to antithrombotic compounds comprising the group Q, Q having formula (I), wherein the substructure (i) is a structure selected from (a, b and c), wherein X is O or S; X? being independently CH or N; and m is 0, 1, 2 or 3; wherein the group Q is bound through an oxygen atom or an optionally substituted nitrogen or carbon atom, or a pharmaceutically acceptable salt thereof or a prodrug thereof. The compounds of the invention are therapeutically active and in particular are antithrombotic agents.

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Reference:
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis—I. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis