The fractal brain: scale-invariance in structure and dynamics.

The past 40 years have witnessed extensive research on fractal structure and scale-free dynamics in the brain. Although considerable progress has been made, a comprehensive picture has yet to emerge, and needs further linking to a mechanistic account of brain function. Here, we review these concepts, connecting observations across different levels of organization, from both a structural and functional perspective.

The impact of automated hippocampal volumetry on diagnostic confidence in patients with suspected Alzheimer's disease: A European Alzheimer's Disease Consortium study.

Introduction: Hippocampal volume is a core biomarker of Alzheimer's disease (AD). However, its contribution over the standard diagnostic workup is unclear.

Methods: Three hundred fifty-six patients, under clinical evaluation for cognitive impairment, with suspected AD and Mini-Mental State Examination ≥20, were recruited across 17 European memory clinics.

The synthesis and biological evaluation of quinolyl-piperazinyl piperidines as potent serotonin 5-HT1A antagonists.

As part of an effort to identify 5-HT(1A) antagonists that did not possess typical arylalkylamine or keto/amido-alkyl aryl piperazine scaffolds, prototype compound 10a was identified from earlier work in a combined 5-HT(1A) antagonist/SSRI program. This quinolyl-piperazinyl piperidine analogue displayed potent, selective 5-HT(1A) antagonism but suffered from poor oxidative metabolic stability, resulting in low exposure following oral administration. SAR studies, driven primarily by in vitro liver microsomal stability assessment, identified compound 10b, which displayed improved oral bioavailability and lower intrinsic clearance.

Discovery and optimization of 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR).

We discovered 2-(4-substituted-pyrrolo[2,3-b]pyridin-3-yl)methylene-4-hydroxybenzofuran-3(2H)-ones as potent and selective ATP-competitive inhibitors of the mammalian target of rapamycin (mTOR). Since phenolic OH groups pose metabolic liability, one of the two hydroxyl groups was selectively removed. The SAR data showed the structural features necessary for subnanomolar inhibitory activity against mTOR kinase as well as selectivity over PI3Kalpha.

The identification of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamines as potent inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1).

A series of 8,9-dimethoxy-5-(2-aminoalkoxy-pyridin-3-yl)-benzo[c][2,7]naphthyridin-4-ylamine-based inhibitors of 3-phosphoinositide-dependent kinase-1 (PDK-1) has been identified. Several examples appear to be potent and relatively selective inhibitors of PDK-1 over the related AGC kinases PKA, PKB/AKT, and p70S6K. The introduction of a stereochemical center beside the amino substituent on the aminoalkoxy-side chain had little effect upon the inhibitory activity against these enzymes, and X-ray crystallographic analyses of a representative pair of enantiomeric inhibitors bound to the active site of PDK-1 revealed comparable binding modes for each enantiomer.

(4-Substituted-phenyl)-(5H-10,11-dihydro-pyrrolo [2,1-c][1,4] benzodiazepin-10-yl)-methanone derivatives as vasopressin receptor modulators.

Synthesis and structure-activity relationships (SAR) of arginine vasopressin (AVP) receptor modulators are described. Potent and selective compounds are prepared when the amide linkage connecting rings A and B of VPA-985 is replaced with a bond, CO, -O-, -S-, or -SO2- bond.

Synthesis and structure-activity relationships of 4-alkynyloxy phenyl sulfanyl, sulfinyl, and sulfonyl alkyl hydroxamates as tumor necrosis factor-alpha converting enzyme and matrix metalloproteinase inhibitors.

A series of 4-alkynyloxy phenyl sulfanyl, sulfinyl and sulfony alkyl and piperidine-4-carboxylic acid hydroxamides were synthesized. Their structure-activity relationships, against tumor necrosis factor-alpha (TACE) and matrix metalloproteinase (MMP) inhibitor activities, are presented by investigating the oxidation state on sulfur and altering the P1' substituent. The sulfonyl derivatives 20-24 carrying a 4-butynyloxy moiety were selective TACE inhibitors over the MMPs tested.

Structure-activity study of novel tricyclic benzazepine arginine vasopressin antagonists.

Novel tricyclic benzazepine derivatives were synthesized as arginine vasopressin (AVP) antagonists. Several tricyclic compounds showed potent antagonistic activity in rat AVP receptors V(1a) and V(2). Derivatives containing pyrrolo-tricyclic amines, 13i-k, 30, and 31 also showed selectivity for the V(2) receptor.

Synthesis and structure-activity relationship of N-substituted 4-arylsulfonylpiperidine-4-hydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis.

The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. In our preceding paper, we have reported on a series of novel and orally active N-hydroxy-alpha-phenylsulfonylacetamide derivatives. However, these compounds had two drawbacks (moderate selectivity and chirality issues).

Synthesis and structure-activity relationship of alpha-sulfonylhydroxamic acids as novel, orally active matrix metalloproteinase inhibitors for the treatment of osteoarthritis.

The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. These enzymes are strictly regulated by endogenous inhibitors such as tissue inhibitors of MMPs and alpha(2)-macroglobulins. Overexpression of these enzymes has been implicated in various pathological disorders such as arthritis, tumor metastasis, cardiovascular diseases, and multiple sclerosis.

[In vitro antimicrobial activity of new 1,10-phenantroline derivatives].

The antimicrobial and antifungical activities of some 1,10-phenanthroline derivatives are described. The test was performed using the diffusimetric method with stainless steel cylinders based on diffusion of the substances on the gelose surface for bacteria and Sabouraud field for Candida Albicans yeast. The comparative analysis of the obtained data leads to the following conclusions concerning the relation between structure and activity

Tetrazolium salts and metal complexes of some formazans.

This paper presents the synthesis of some tetrazolium salts and metal complexes combinations, which are derived from aromatic and heterocyclic formazans. Elemental quantitative analyses and spectral data confirmed the structure of the new synthesized compounds. The new synthesized compounds were submitted to microbiological tests.

[Hydrazide derivatives with biologically active 1,2,4-triazole support].

This study presents the synthesis of ten new hydrazides with 1,2,4-triazole support. The structures of the obtained compounds were elucidates by means of the elemental analysis data as well as by IR spectral measurements. The antimicrobial and antifungal actions of this derivates are also tested.

[New derivatives of 1-methyl-phthalazine with antimicrobial and fungistatic action].

In this paper we present the antimicrobial and antifungical action of some new salts of 1-methyl-phtalaziniums and their corresponding ylids. We also present conclusions concerning the relation between structure and biological activity. The test was performed using the diffusimetric method with rustless steel cylinders based on the diffusion on the tested substances on gelose surface.

Prodrugs of CL316243: a selective beta3-adrenergic receptor agonist for treating obesity and diabetes.

CL316243 is a highly selective and potent beta3-adrenergic receptor agonist, and has been shown in rodent models to be an effective agent for treating obesity and Type II diabetes. To improve the oral absorption and pharmacokinetic profiles of CL316243, a number of prodrugs have been synthesized and evaluated. Several ester-type prodrugs show significant improvements in oral bioavailability in both rodent and primate models.

5-fluoro-2-methyl-N-[5-(5H-pyrrolo[2,1-c][1,4]benzodiazepine-10(11H)-yl carbonyl)-2-pyridinyl]benzamide (CL-385004) and analogs as orally active arginine vasopressin receptor antagonists.

Synthesis and structure-activity relationships (SAR) of orally active arginine vasopressin (AVP) receptor antagonists are discussed. Potent and orally active AVP receptor antagonists are produced when ring A of VPA-985 (1) is replaced with a 3-pyridinyl unit (2b).

4,10-dihydro-5H-thieno[3,2-c][1]benzazepine derivatives and 9,10-dihydro-4H-thieno[2,3-c][1]benzazepine derivatives as orally active arginine vasopressin receptor antagonists.

Synthesis and structure-activity relationships (SAR) of arginine vasopressin receptor (AVP) antagonists are described. Potent and orally active compounds are prepared when tricyclic 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine moiety in VPA-985 1 is replaced with a compound 7 or 12.

[Antimicrobial activity of some derivatives of pyrimidine].

In this paper the authors present the antimicrobial and antifungical tests of some new 3-methylpyrimidine compounds. The test was performed using the diffusimetric method with rustlessteel cylinders based on the diffusion of the tested substances on the gelose surface. The comparative analysis of the obtained data leads to the following conclusions concerning the relation between structure and biological activity in the pyrimidine series: 1.

Hydrazones and formazans with possible biological activity.

This paper presents a synthesis about some hydrazones, formazans and copper's complexes combinations. The structure of the new compounds was confirmed by the results of the quantitative elementary and IR spectral analysis. The antimicrobial and antiinflammatory activities were investigated.

Visual processing of configuration-dependent spatial characteristics of shapes and patterns. A model useful in the study of the role of the departure from circularity or dispersion of shapes in human visual perception.

In this work a theoretical model was used in combination with testings on normal subjects to get more insight in the role of the departure from circularity or dispersion of the shapes in visual perception. The model was inspired by the observation that the intensity of the effect of a given level of contrast of a shape usually increases, for the same area, with the shape being better concentrated around a center. The model introduces as a measurable characteristic the degree of concentration or dispersion of a shape with respect to a center.

[Antimicrobial activity of new pyridazine derivatives].

Continuing the investigations concerning synthesis-structure-biological activity in the pyridazine series, the results of the antimicrobial and antifungal tests of some new pyridazinium compounds are presented. The test was performed using the diffusimetric method with rustles steel cylinders based on the diffusion of the tested substances on the gelose surface. The comparative analysis of the obtained data leads to the following conclusions concerning the relation between structure and activity in the pyridazine series: 1.

[The synthesis and biological activity of new disubstituted carbanion ylides from pyridazine].

Continuing the investigations in view obtaining new carbon-nitrogen stable dissiniu-ilydes, were obtained new 3-phenyle-pyridaziniu-ylides carbanion disubstituted. The antimicrobial and antifungus action of the products VIa, VIb, VIIa, VIIb and VIIc also studied.

[The antibacterial action of new hydrazide derivatives].

New derivatives of 4-aminobenzoic and 4-chlorine-2-hydroxybenzoic acids hydrazides were synthesized by the condensation reaction of these hydrazides with aldehydes and ketones, derivatives containing in their molecule azometine and hydrazone groups. The obtained products are potentially bioactive. The study of their "in vitro" biological activity was performed on some pathogenic germs, both gram-positive and gram-negative.

[Phthalazinilides. The action of ethyl bromopyruvate on phthalazine].

Our investigation for obtaining carbon-nitrogen stable ilides continued by the synthesis of new phthalazinic derivatives by the action of ethyl brompyruvate. The structure of the obtained products was confirmed by chemical and spectral analyses. The results regarding their antimicrobial action are also presented.