cas 5398-44-7, 2,6-Dichloroisonicotinic acid

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Methylsulfanylpyridine based diheteroaryl isocombretastatin analogs as potent anti-proliferative agents
Isocombretastatins are the not isomerizable 1,1-diarylethene isomers of combretastatins. Both families of antimitotics are poorly soluble and new analogs with improved water solubility are needed. The ubiquitous 3,4,5-trimethoxyphenyl ring and most of its replacements contribute to the solubility problem. 39 new compounds belonging to two series of isocombretastatin analogs with 2-chloro-6-methylsulfanyl-4-pyridinyl or 2,6-bis(methylsulfanyl)-4-pyridinyl moieties replacing the 3,4,5-trimethoxyphenyl have been synthesized and their antimitotic activity and aqueous solubility have been studied. We show here that 2-chloro-6-methylsulfanylpyridines are more successful replacements than 2,6-bis(methylsulfanyl)pyridines, giving highly potent tubulin inhibitors and cytotoxic compounds with improved water solubilities. The optimal combination is with indole rings carrying polar substitutions at the three position. The resulting diheteroaryl isocombretastatin analogs showed potent cytotoxic activity against human cancer cell lines caused by tubulin inhibition, as shown by in vitro tubulin polymerization inhibitory assays, cell cycle analysis, and confocal microscopy studies. Cell cycle analysis also showed apoptotic responses following G2/M arrest after treatment. Conformational analysis and docking studies were applied to propose binding modes of the compounds at the colchicine site of tubulin and were in good agreement with the observed SAR. 2-Chloro-6-methylsulfanylpyridines represent a new and successful trimethoxyphenyl ring substitution for the development of improved colchicine site ligands.
álvarez, Raquel,Aramburu, Laura,Gajate, Consuelo,Vicente-Blázquez, Alba,Mollinedo, Faustino,Medarde, Manuel,Peláez, Rafael
(2021)
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Exceptionally high temperature spin crossover in amide-functionalised 2,6-bis(pyrazol-1-yl)pyridine iron(ii) complex revealed by variable temperature Raman spectroscopy and single crystal X-ray diffraction
The synthesis of a novel amide-functionalised 2,6-bis(pyrazol-1-yl)pyridine-4-carboxamide ligand (bppCONH2) is described. The complex salts [Fe(bppCONH2)2](BF4)2and [Fe(bppCONH2)2](ClO4)2were synthesised and characterised by SQUID magnetometry, differential scanning calorimetry, variable temperature Raman spectroscopy and single crystal X-ray diffraction. DSC measurements of [Fe(bppCONH2)2](BF4)2indicate a spin-crossover (SCO) transition withT↑ at 481 K andT↓ at 461 K, showing a 20 K hysteresis. DSC for the perchlorate salt shows an SCO transition withT↑ at 459 K andT↓ at 445 K with a 14 K hysteresis. For the BF4?salt analysis of low and high-spin state crystal structures at 101, 290 and 500 K, suggest stabilisation of the low spin state due to the formation of 1D hydrogen-bonded cationic chains. Variable temperature Raman studies of the BF4salt support the presence of a high temperature SCO. It is speculated that the presence of hysteresis may be attributed to differences in the inter-molecular hydrogen bonding in the low spin and high spin states.
Akutsu, Hiroki,Attwood, Max,Blundell, Toby J.,Le Maguere, Pierre,Martin, Lee,Turner, Scott S.
supporting information
p. 11843 - 11851
(2021/09/06)

Preparation method of 4-amino-2,6-dichloropyridine
The invention relates to a preparation method of a halogen-substituted pyridylamine compound, particularly to a preparation method of 4-amino-2,6-dichloropyridine, wherein 2,6-dihydroxy isonicotinic acid is used as a raw material and is subjected to chlorination reaction, Curtius rearrangement or further amine protection group removal to obtain the product. The method has the advantages of accessible raw materials, high yield and low impurity content, avoids the use of explosive reagent sodium azide, and can be further applied to industrial production.
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Paragraph 0108-0110

(2021/03/21)

An alternate and efficient method for preparation of 2,6-diacetamido-4-formylpyridine for formation of porphyrin appended with hydrogen bonding motifs
We report here an alternate redesigned five-step synthesis of 2,6-diacetamido-4-formylpyridine. The method described here is more convenient where this aldehyde is prepared in commercially viable quantities from simple and easy-to-use reagents and is a key compound required to prepare 5,10,15,20-Tetrakis(3,5-diacetamido-4-pyridyl)porphyrin (I). This porphyrin can be used as an excellent building block for the construction of supramolecular assemblies and is an interesting compound to study the design, principles, and photonic properties such as the extent of electron and energy transfer.
Singh, Sunaina,Aggarwal, Amit,Mercier, Phillippe H.,Bhupathiraju, N. V. S. Dinesh K.,Landress, Michael,Hanna, Keroles
p. 3256 - 3263
(2020/08/05)

Potent colchicine-site ligands with improved intrinsic solubility by replacement of the 3,4,5-trimethoxyphenyl ring with a 2-methylsulfanyl-6-methoxypyridine ring
Colchicine site antimitotic agents typically suffer from low aqueous solubilities and are formulated as phosphate prodrugs of phenolic groups. These hydroxyl groups are the aim of metabolic transformations leading to resistance. There is an urgent need for more intrinsically soluble analogues lacking these hydroxyl groups. The 3,4,5-trimethoxyphenyl ring of combretastatin A-4 is a liability in terms of solubility but it is considered essential for high cytotoxic and tubulin polymerization inhibitory (TPI) activity. We have synthesized 36 new analogues of combretastatin A-4 replacing the trimethoxyphenyl moiety with more polar pyridine based moieties, measured their aqueous solubility, and studied their anti-proliferative effects against 3 human cancer cell lines. We show here that pyridine rings can be successful replacements for the trimethoxyphenyl ring, resulting in potent and more soluble analogues. The more straightforward replacement, a 2,6-dimethoxypyridine ring led to inactive analogues, but a 2-methoxy-6-methylsulfanylpyridine moiety led to active analogues when combined with different B rings. This replacement led to potent cytotoxic activity against sensitive human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies. Cell cycle analysis also showed apoptotic responses following treatment. Docking studies suggested binding at the colchicine site of tubulin and provided a good agreement with the observed SAR. A 2-methoxy-6-methylsulfanylpyridine moiety is a good trimethoxyphenyl ring replacement for the development of new colchicine site ligands.
Aramburu, Laura,Gajate, Consuelo,Medarde, Manuel,Mollinedo, Faustino,álvarez, Raquel,Peláez, Rafael,Vicente-Blázquez, Alba
(2020/03/27)

Self-assembly formation of a healable lanthanide luminescent supramolecular metallogel from 2,6-bis(1,2,3-triazol-4-yl)pyridine (btp) ligands
The synthesis of five new 2,6-bis(1,2,3-triazol-4-yl)pyridine (btp) ligands is described: the self-assembly behaviour of the tri-methyl ester, 1, with Eu(iii) showed the formation of a luminescent 1 : 3 Eu : btp complex, Eu13, which was studied in solution and in the solid state; while the tri-carboxylic acid, 2, formed a hydrogel and its corresponding complex Eu23, gave rise to a strongly red luminescent healable metallogel.
McCarney, Eoin P.,Byrne, Joseph P.,Twamley, Brendan,Martínez-Calvo, Miguel,Ryan, Gavin,M?bius, Matthias E.,Gunnlaugsson, Thorfinnur
supporting information
p. 14123 - 14126
(2015/09/15)

Design and structural analysis of aromatic inhibitors of type II dehydroquinase from mycobacterium tuberculosis
3-Dehydroquinase, the third enzyme in the shikimate pathway, is a potential target for drugs against tuberculosis. Whilst a number of potent inhibitors of the Mycobacterium tuberculosis enzyme based on a 3-dehydroquinate core have been identified, they generally show little or no in vivo activity, and were synthetically complex to prepare. This report describes studies to develop tractable and drug-like aromatic analogues of the most potent inhibitors. A range of carbon-carbon linked biaryl analogues were prepared to investigate the effect of hydrogen bond acceptor and donor patterns on inhibition. These exhibited inhibitory activity in the high-micromolar range. The addition of flexible linkers in the compounds led to the identification of more potent 3-nitrobenzylgallate- and 5-aminoiso-phthalate-based analogues.
Howard, Nigel I.,Dias, Marcio V.B.,Peyrot, Fabienne,Chen, Liuhong,Schmidt, Marco F.,Blundell, Tom L.,Abell, Chris
p. 116 - 133
(2015/04/14)

Synthesis and antimicrobial activities of some newly 2,4,6-tri-substituted pyridine derivatives
A series of novel 2-(2-(substituted benzylidene)hydrazinyl)-N'-(substituted benzylidene)-6-chloropyridine-4-carbohydrazide (5a-e), 2-(2- cycloalkylidenehydrazinyl)-6-chloro-N'-cyclo-alkylidenepyridine-4- carbohydrazide (6a,b), 2-(2-(1-(4-substituted phenyl)ethylidene)hydrazinyl)-6- chloro-N'-(1-(4-substituted phenyl)ethylidene)pyridine-4-carbohydrazide (7a,b) and 2-(2-(1-(pyridinyl)ethylidene)hydrazinyl)-6-chloro-N'-(1-(pyridinyl) ethylidene)pyridine-4-carbo-hydrazide (8a-c) derivatives have been synthesized by treating treating 2-chloro-6-hydrazinoisonicotinic acid hydrazide 4 with selected active reagents. Their structures were confirmed by spectral and analytical data. The synthesized compounds were investigated for antimicrobial activities. The antimicrobial screening showed that many of these obtained compounds have good activities comparable to Streptomycin and Fusidic acid as reference drugs. Springer Science+Business Media Dordrecht 2013.
Abdel Salam, Osama I.,Khalifa, Nagy M.,Said, Said A.,Amr, Abd El-Galil E.
p. 1147 - 1155
(2014/05/06)

BICYCLIC INHIBITORS OF ALK
The present invention relates to compounds of formula (1) or pharmaceutical acceptable salts, Formula (1) wherein R1, R2, R3, X, Y, Z, A, B, G1, m, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as ALK and methods of treating diseases such as cancer.
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Paragraph 0312

(2014/06/25)

Optimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal Structure Analysis with Human CathepsinL
The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 substituent led to high-affinity ligands with inhibition constants down to 2nM for compounds bearing cyclohexyl substituents. Systematic investigations on the S3 pocket revealed its potential to achieve high activities with aromatic vectors that undergo stacking interactions with the planar peptide backbone forming part of the pocket. X-ray crystal structure analysis with the structurally related enzyme human cathepsinL confirmed the binding mode of the triazine ligand series as proposed by molecular modeling. Sub-micromolar inhibition of the proliferation of cultured parasites was achieved for ligands decorated with the best substituents identified through the optimization cycles. In cell-based assays, the introduction of a basic side chain on the inhibitors resulted in a 35-fold increase in antitrypanosomal activity. Finally, bioisosteric imidazopyridine nitriles were studied in order to prevent off-target effects with unselective nucleophiles by decreasing the inherent electrophilicity of the triazine nitrile headgroup. Using this ligand, the stabilization by intramolecular hydrogen bonding of the thioimidate intermediate, formed upon attack of the catalytic cysteine residue, compensates for the lower reactivity of the headgroup. The imidazopyridine nitrile ligand showed excellent stability toward the thiol nucleophile glutathione in a quantitative invitro assay and fourfold lower cytotoxicity than the parent triazine nitrile.
Ehmke, Veronika,Winkler, Edwin,Banner, David W.,Haap, Wolfgang,Schweizer, W. Bernd,Rottmann, Matthias,Kaiser, Marcel,Freymond, Celine,Schirmeister, Tanja,Diederich, Francois
supporting information
p. 967 - 975
(2013/07/27)

BICYCLIC INHIBITORS OF ALK
The present invention relates to compounds of formula (1) or pharmaceutical acceptable salts, wherein R1, X, Y, Z, A, B, G1, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as ALK and methods of treating diseases such as cancer.
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(2012/08/07)

BICYCLIC INHIBITORS OF ANAPHASTIC LYMPHOMA KINASE
Disclosed are compounds of formula (Ⅰ) and their pharmaceutical acceptable salts, wherein R1, R2, R3, X, Y, Z, A, B, G1, m and n are defined in the description. The compositions containing the said compounds used for inhibiting kinases such as anaphastic lymphoma kinase (ALK) and methods of treating diseases such as cancer are disclosed.
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(2012/08/07)

BICYCLIC INHIBITORS OF ALK
The present invention relates to compounds of formula (1) or pharmaceutical acceptable salts, Formula (1) wherein R1, R2, R3, X, Y, Z, A, B, G1, m, and n are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as ALK and methods of treating diseases such as cancer.
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Page/Page column 72-73

(2012/08/07)

Titanocene(III)-catalyzed conversion of N-(epoxyalkyl)anilines into indolines
Densely substituted indolines and azaindolines can be obtained by the titanocene(III) chloride catalyzed reductive opening of N-(oxiran-2-ylmethyl) anilines. The reaction optimization, substrate scope, and limitations are discussed, and a mechanistic pathway for the epoxideopening rearrangement is proposed. ARKAT-USA, Inc.
MacIejewski, John P.,Wipf, Peter
experimental part
p. 92 - 119
(2011/06/20)

Convenient synthesis of tridentate 2,6-di(pyrazol-1-yl)-4-carboxypyridine and tetradentate 6,6′-di(pyrazol-1-yl)-4,4′-dicarboxy-2,2′- bipyridine ligands
Citrazinic acid is used as a convenient starting material for both tridentate 2,6-di(pyrazol-1-yl)-pyridine and tetradentate 6,6′-di(pyrazol- 1-yl)-2,2′-bipyridine ligands containing carboxylic groups useful for further anchoring of sensitizer on TiO2 for dye-sensitized solar cells (DSCs). Using 2,6-dichloro-4-carboxypyridine, the synthesis of the terdentate ligands was improved compared to previously used 2,6-dibromo-4- carboxypyridine or 2,6-dichloro-4-ethylcarboxylate pyridine. Controlling the reaction conditions, it is possible to efficiently obtain the monosubstituted 2-chloro-6-pyrazol-1-yl-4-carboxypyridine, a key intermediate for the preparation of tetradentate 6,6′-di(pyrazol-1-yl)-4,4′-dicarboxy-2, 2′-bipyridine ligand.
Klein, Cédric,Baranoff, Etienne,Gr?tzel, Michael,Nazeeruddin, Md. Khaja
experimental part
p. 584 - 587
(2011/03/18)

6-Amino-4-(pyrimidin-4-yl)pyridones: Novel glycogen synthase kinase-3β inhibitors
The synthesis and structure-activity relationships for a novel series of 6-amino-4-(pyrimidin-4-yl)pyridones derived from a high throughput screening hit are discussed. Optimization of lead matter afforded compounds with good potency, selectivity and central nervous system (CNS) exposure.
Coffman, Karen,Brodney, Michael,Cook, James,Lanyon, Lorraine,Pandit, Jayvardhan,Sakya, Subas,Schachter, Joel,Tseng-Lovering, Elaine,Wessel, Matthew
scheme or table
p. 1429 - 1433
(2011/04/23)

Efficient discovery of fluorescent chemosensors based on a biarylpyridine scaffold
(Figure Presented) The discovery of several fluorescent chemosensors for Hg(II) and Ag(I) In mixed aqueous solution Is reported. The ease with which these fluorlonophores were prepared from a common core underscores the utility of conformational restriction as a signaling mechanism. In addition, for the first time, significant changes were observed In biarylpyridlne emission wavelength, allowing ratlometric detection of Hg(II) and Ag(I). Finally, on the basis of computational analyses, beneficial structural modifications were predicted for the next generation of chemosensors.
Malashikhin, Sergey A.,Baldridge, Kim K.,Finney, Nathaniel S.
supporting information; scheme or table
p. 940 - 943
(2010/06/16)

Titanocene(III)-catalyzed formation of indolines and azaindolines
(Chemical Equation Presented) Reductive cyclization of epoxides tethered to substituted anilines and aminopyridines in the presence of 3 mol % of titanocene dichloride and stoichiometric manganese metal promotes a radical annulation to form 3,3-disubstituted indolines and azaindolines.
Wipf, Peter,Maciejewski, John P.
supporting information; experimental part
p. 4383 - 4386
(2009/05/30)

Antianexiety activity of pyridine derivatives synthesized from 2-chloro-6-hydrazino-isonicotinic acid hydrazide
A series of oxadiazole pyridine derivatives were synthesized by using 2-chloro-6-hydrazinoisonicotinic acid hydrazide as starting material. Treatment of the hydrazide with carbon disulfide to afford the oxadiazole derivative, which was treated with 5-methyl-2-furancarbaldehyde, formic acid, acetic acid/acetic anhydride, or phthalic anhydride to yield the corresponding pyridinodiazoles and on imide. Condensation of the hydrazide with p-fluorobenzaldehyde in ethanol or acetic acid in the presence of sodium acetate afforded hydrazone and oxadiazole derivatives, which were acetylated and cyclized with acetic anhydride to N-acetyloxadiazole derivatives. The hydrazone was treated with acetic acid in the presence of sodium acetate, or bromine water/sodium acetate to give on oxadiazole, while it was cyclized with chloroacetyl chloride in the presence of TEA to oxoazetidinaminoisonicotinamide. Finally, condensation of the hydrazide with acid anhydrides in refluxing glacial acetic acid afforded the corresponding bisimide derivatives. The pharmacological screening showed that many of these obtained compounds have good antianexiety activity comparable to diazepam as positive control.
Amr, Abd El-Galil E.,Mohamed, Salwa F.,Abdel-Hafez, Naglaa A.,Abdalla, Mohamed M.
scheme or table
p. 1491 - 1498
(2009/12/05)

Synthesis, and analgesic and antiparkinsonian activities of thiopyrimidine, pyrane, pyrazoline, and thiazolopyrimidine derivatives from 2-chloro-6-ethoxy-4-acetylpyridine
A series of substituted pyridine derivatives were prepared from 2-chloro-6-ethoxy-4-acetylpyridine, which was prepared from the corresponding citrazinic acid as starting material. Reaction of acetylpyridine with thiophene-2-carboxaldehyde afforded the 2-chloro-6-ethoxy-4-β-(2-thienyl) acryloylpyridine, which was reacted with malononitrile in refluxing ethanol in the presence of piperidine as a catalyst to afford the cyanoaminopyrane derivative. Acryloylpyridine was treated with urea or guanidine hydrochloride in refluxing ethanolic potassium hydroxide to give the corresponding pyrimidinone and aminopyrimidine derivatives. The latter was condensed with hydrazine hydrate or phenyl hydrazine to give pyrazoline and N-phenylpyrazoline derivatives. Finally, cycloaddition reaction of acryloylpyridine with thiourea yielded thioxopyrimidine, which was treated with 2-bromopropionic acid, 3-bromopropionic acid, or bromoacetic acid to yield methylthiazolo-, thiazino-, and thiazolopyrimidine derivatives. The arylmethylene derivative was prepared by reacting thiazolopyrimidine with benzaldehyde or by reacting thioxopyrimidine with benzaldehyde and bromoacetic acid in one step. The pharmacological screening showed that many of these compounds have good analgesic and antiparkinsonian activities comparable to Valdecoxib and Benzatropine as reference drugs.
Amr, Abd El-Galil E.,Maigali, Soher S.,Abdulla, Mohamed M.
scheme or table
p. 1409 - 1415
(2009/12/08)

Synthesis of 2,6-di(pyrazol-1-yl)-4-bromomethylpyridine, and its conversion to other 2,6-di(pyrazol-1-yl)pyridines substituted at the pyridine ring
Two routes to 2,6-di(pyrazol-1-yl)-4-hydroxymethylpyridine (1) from 2,6-dihydroxy-isonicotinic acid, in four and six steps, are reported. Reaction of 1 with 48% HBr yields 2,6-di(pyrazol-1-yl)-4-bromomethylpyridine (2), which is a powerful precursor to a range of new tridentate ligands for transition metals functionalised at the pyridine ring. As a proof of principle, we describe the further elaboration of 2 to give two 2,6-di(pyrazol-1-yl)pyridines bearing nucleobase substituents, and the back-to-back ligand 1,2-bis[2,6-di(pyrazol-1-yl)pyrid-4-yl]ethane. Crystal structures of two of these new derivatives are presented.
Elha?k, Jér?me,Pask, Christopher M.,Kilner, Colin A.,Halcrow, Malcolm A.
p. 291 - 298
(2007/10/03)

Reversing the discovery paradigm: A new approach to the combinatorial discovery of fluorescent chemosensors
We report here a new approach to the discovery of fluorescent chemosensors in which a new signaling mechanism allows a core fluorophore to be used in a combinatorial search for new binding events, thus reversing the reigning discovery paradigm. Copyright
Mello, Jesse V.,Finney, Nathaniel S.
p. 10124 - 10125
(2007/10/03)

Salicylate activity. 3. Structure relationship to systemic acquired resistance
Salicylic acid (2-hydroxybenzoic acid; SA) is a primary signal inducing plant defenses against pathogens. This plant disease resistance, known as systemic acquired resistance (SAR), is an attractive target for the development of new plant protection agents. SAR induction is a multistep process that includes accumulation of pathogenesis-related (PR) proteins. The structure-activity profile of salicylates and related compounds has been evaluated using an inducible PR protein (PR-1a) and plant resistance to tobacco mosaic virus (TMV) as markers. Among the 47 selected monosubstituted and multiple-substituted salicylate derivatives tested, all 8 derivatives that induced more PR-1a protein than SA were fluorinated or chlorinated in the 3- and/or 5-position (3,5-difluorosalicylate > 3-chlorosalicylate > 5-chlorosalicylate > 3,5-dichlorosalicylate > 3-chloro-5-fluorosalicylate > 3-fluorosalicylate > 3-fluoro-5-chlorosalicylate > 3,5-dichloro-6-hydroxysalicylate > SA). In general, substitutions for or on the 2-hydroxyl group or at the 4-position of the ring reduced or eliminated PR-1a protein induction. In contrast, substitutions in positions ortho (3-position) or para (5-position) to the hydroxyl group with electron-withdrawing groups other than chlorine or fluorine decreased induction, and electron-donating groups in these positions also had a deleterious effect on PR-1a induction. PR-1a protein accumulation and reduction in TMV lesion diameter exhibited a log-linear relationship. The seven salicylate derivatives that were the most active TMV resistance inducers were all halogenated in the 3- and/or 5-position (3-chlorosalicylate > 3,5-difluorosalicylate > 3,5-dichloro-6-hydroxysalicylate > 3,5,6-trichlorosalicylate > 5-chlorosalicylate > 5-fluorosalicylate > 3,5-dichlorosalicylate > 4-fluorosalicylate > 3-fluorosalicylate > 3-chloro-5-fluorosalicylate > 4-chlorosalicylate > SA). The correlation between PR-1a protein induction and resistance to TMV confirms the value of using PR-1a induction as a screening tool for developing new plant disease control agents.
Silverman, F. Paul,Petracek, Peter D.,Heiman, Daniel F.,Fledderman, Christina M.,Warrior, Prem
p. 9775 - 9780
(2007/10/03)

ARYLPYRIDINE COMPOUNDS
The present invention relates to arylpyridine compounds and methods of using them.
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Page 33-34; 39-40

(2010/02/07)

NOVEL INDOLE DERIVATES AS FABP-4 INHIBITORS
The present invention relates to novel compounds (I) wherein R0, R1, R2, R3, R4, R5, R6, R7, R8, A, B, n, X, and Y are as defined in the description and claims; and also to pharmaceutical compositions comprising the compounds, as well as to the use of the compounds in medicine and for the preparation of a medicament, which acts on the fatty acid binding protein FABP-4. The present invention relates to novel compounds (I) wherein R0, R1, R2, R3, R4, R5, R6, R7, R8, A, B, n, X, and Y are as defined in the description and claims; and also to pharmaceutical compositions comprising the compounds, as well as to the use of the compounds in medicine and for the preparation of a medicament, which acts on the fatty acid binding protein FABP-4.
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Page 35

(2010/02/07)

Exploiting the versatile assembly of arylpyridine fluorophores for wavelength tuning and SAR
(Matrix presented) The facile modular assembly of polyarylpyridine fluorophores provides two important advantages in the development of fluorescent chemosensors: it allows rapid dissection of the structural requirements for fluorescent chemosensing and it allows dramatic tuning of emission wavelength by changes in a substituent remote from the binding site.
Fang, Albert G.,Mello, Jesse V.,Finney, Nathaniel S.
p. 967 - 970
(2007/10/03)

Nonproteinogenic amino acids: An efficient asymmetric synthesis of (S)-(-)-acromelobic acid and (S)-(-)-acromelobinic acid
An efficient synthesis of (S)-(-)-acromelobic acid (1) and (S)-(-)-acromelobinic acid (2) is described via asymmetric hydrogenation protocol. Asymmetric hydrogenation of dehydroamino acid derivative 23 using (R,R)-[Rh(DIPAMP)(COD)]BF4 catalyst followed by removal of the protective groups afforded (S)-(-)-acromelobic acid (1) in >98% ee. The key intermediate 23 was prepared from citrazinic acid (8). The dehydroamino acid derivative 33 required for the synthesis of (S)-(-)-2 was prepared from 2,5-lutidine (27), which upon hydrogenation using (S,S)-[Rh(Et-DuPHOS)(COD)]BF4 catalyst afforded (S)-(+)-34 in 93% yield and >96% ee. Removal of protective groups in (S)-(+)-34 afforded (S)-(-)-acromelobinic acid (2) in good overall yield.
Adamczyk, Maciej,Akireddy, Srinivasa Rao,Reddy, Rajarathnam E
p. 6951 - 6963
(2007/10/03)

Convenient synthesis and transformation of 2,6-dichloro-4-iodopyridine
(Matrix Presented) We describe a convenient scalable synthesis of 2,6-dichloro-4-iodopyridine and demonstrate its utility by stepwise elaboration to a number of 2,4,6-trisubstituted pyridines.
Mello, Jesse V.,Finney, Nathaniel S.
p. 4263 - 4265
(2007/10/03)

A convenient synthesis of [2,6-14C]-2-chloroisonicotinic acid
[2,6-14C]-2-chloroisonicotinic acid (1) was prepared by kinetically controlled lithiation and carbonation of [2,6-14C]-2,6-dichloropyridine, followed by reduction using hydrazine and potassium hydroxide. Copyright
Kelly, Terence P.,Rodgers, Thomas R.,Wright, Christopher
p. 451 - 457
(2007/10/03)

Strategies for the selective functionalization of dichloropyridines at various sites
Whereas 2,3-dichloropyridine and 2,5-dichloro-4-(lithiooxy)-pyridine undergo deprotonation exclusively at the 4- and 2-positions, respectively, optional site selectivity can be implemented with 2,5- and 3,4-dichloropyridine (which are attacked, depending on the choice of the reagents, at either the 4- or 6- and either the 2- and 5-positions, respectively). Upon treatment with lithium diisopropylamide, 2,4-dichloro-3-iodopyridine, 3,5-dichloro-4-bromopyridine and 2,6-dichloro-3-iodopyridine afford 5-, 2- and 4-lithiated intermediates, but the latter isomerize instantaneously to species in which lithium and iodine have swapped places, the driving force being the low basicity of C-Li bonds when flanked by two neighboring halogens.
Marzi, Elena,Bigi, Anna,Schlosser, Manfred
p. 1371 - 1376
(2007/10/03)

An efficient enantioselective synthesis of (S)-(-)-acromelobic acid
(Equation Presented) A highly efficient enantioselective synthesis of (S)-(-)-acromelobic acid (1) was achieved via asymmetric hydrogenation of dehydroamino acid derivative (3) using (R,R)-[Rh(DIPAMP)(COD)]BF4 catalyst followed by removal of protective groups in >98% ee and good over all yield. The key intermediate (3) was prepared from the commercially available citrazinic acid (4) in six steps.
Adamczyk, Maciej,Akireddy, Srinivasa Rao,Reddy, Rajarathnam E.
p. 3421 - 3423
(2007/10/03)

Electron transfer in a hydrogen-bonded assembly consisting of porphyrin-diimide
Electron-transfer reactions in an H-bonded assembly composed of a diacylaminopyridine bearing zinc porphyrin and 1,8:4,5-naphthalenetetracarboxylic diimide(Ka = 2.8 × 102 dm3 mol-1) in benzene occur with kCS = 4.1 × 1010 s-1 and kCR = 3.7 × 109 s-1, while the corresponding covalently linked model with a comparable distance and energy gap undergoes electron transfer with kCS = 9.9 × 1010 s-1 and kCR = 6.7 × 108 s-1.
Osuka, Atsuhiro,Yoneshima, Ryusho,Shiratori, Hideo,Okada, Tadashi,Taniguchi, Seiji,Mataga, Noboru
p. 1567 - 1568
(2007/10/03)

Practical asymmetric synthesis of (S)-4,ethyl-7,8-dihydro-4-hydroxy-1H- pyrano[3,4-f]indolizine-3,6,10(4H)-trione, a key intermediate for the synthesis of Irinotecan and other camptothecin analogs
A practical asymmetric synthesis of (S) 4-ethyl-7,8-dihydro-4-hydroxy- 1H-pyrano[3,4-f]indolizine-3,6,10(4H)-trione (1), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6- methoxypyridine 5. An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine (6) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert (S)-16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.
Henegar,Ashford,Baughman,Sih,Gu
p. 6588 - 6597
(2007/10/03)