- NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS
-
Novel tricyclic compounds of Formula (I) and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
- -
-
Page/Page column 100
(2015/07/07)
-
- NOVEL TRICYCLIC CALCIUM SENSING RECEPTOR ANTAGONISTS FOR THE TREATMENT OF OSTEOPOROSIS
-
Novel tricyclic compounds of the formula (I): and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing osteoporosis and similar conditions. The compounds are effective as calcium sensing receptor antagonists. Pharmaceutical compositions and methods of treatment are also included.
- -
-
Page/Page column 99
(2015/07/07)
-
- New combination of pharmacophoric elements of potent σ1 ligands: Design, synthesis and σ receptor affinity of aminoethyl substituted tetrahydrobenzothiophenes
-
The aminoethyl substituted tetrahydrobenzothiophenes 4 resulted from combination of the pharmacophoric elements of the potent σ1 ligands 2 and 3. The aminoethyl substituted tetrahydrobenzothiophenes 4 were prepared in an 8-step synthesis starting with thiophene. Whereas the σ1 affinity of the N-benzyl derivative 4a is in the medium nanomolar range (Ki = 49 nM), the analogous N-cyclohexylmethyl derivative 4d exhibits low nanomolar affinity (Ki = 5.0 nM). The reduced σ1 affinity and σ2/σ1 selectivity of tetrahydrobenzothiophenes 4 compared to analogous spirocyclic piperidines 3 is attributed to the increased conformational flexibility of the aminoethyl side chain.
- Harel, Dipak,Schepmann, Dirk,Wünsch, Bernhard
-
p. 490 - 497
(2013/10/22)
-
- COMPOUNDS AND METHODS
-
Disclosed are compounds having the formula: wherein X1, X2, X3, R1, R2, R3, R4, Y, A, n and L are as defined herein, and methods of making and using the same.
- -
-
Page/Page column 60-61
(2011/08/04)
-
- SYNTHESIS OF SUBSTITUTED TETRAHYDROINDENYL COMPLEXES
-
This invention relates to the synthesis of substituted tetrahydroindenyls and the use of the synthesised complexes in the homo- and co-polymerisation of ethylene and alpha-olefins.
- -
-
Page/Page column 17-19
(2010/08/04)
-
- Synthesis and evaluation of some novel isochroman carboxylic acid derivatives as potential anti-diabetic agents
-
A series of novel isochroman mono-carboxylic acid derivatives were synthesized, characterized and evaluated for their ability to inhibit protein tyrosine phosphatase 1B (PTP1B) in vitro in order to use them as potential anti-diabetic agents. Analysis of structure-activity relationships led to the identification of potent compound 4n which inhibited PTP1B with IC50 value of 51.63 ± 0.91 nM. In general, high potency was associated with a dithiolane ring with a spacer of five carbons to the isochroman ring. Compound 4n has been selected for in vivo evaluation as drug candidate for anti-diabetic activity.
- Lakshminarayana,Rajendra Prasad,Gharat, Laxmikant,Thomas, Abraham,Ravikumar,Narayanan, Shridhar,Srinivasan,Gopalan, Balasubramanian
-
scheme or table
p. 3147 - 3157
(2009/12/04)
-
- Synthesis of tri- and tetracyclic heterocycles related to cyclohexa- and cyclohepta[b]thiophenes
-
Synthesis of a number of tri- and tetracyclic compounds with a fused thiophene ring starting from spiro[benzo[b]thiophene-6(5H), 1'-cycloalkyl]-4(7H)-one 1(R = H, Me, Et and n = 4, 5) and cyclohepta[b]thiophenone 2 (R1 = H, R2 = Me and R1R2 = -(CH2)4-) is described.
- Sen,Saha,Das
-
p. 334 - 338
(2007/10/03)
-
- Cyclic bis-urea compounds as gelators for organic solvents
-
The gelation properties of bis-urea compounds derived from optically pure trans-1,2-diaminocyclohexane and 1,2-diaminobenzene, with pendant aliphatic, aromatic, or ester groups, as well as the structure of the resulting gels, have been studied by differential scanning calorimetry, infrared spectroscopy, small-angle X-ray diffraction, and electron microscopy. These compounds have been found to be very potent gelators for organic solvents, such as aliphatic and aromatic hydrocarbons, esters, ketones, and alcohols, at concentrations well below 1 (w/v)%. Gelation by these compounds is completely thermoreversible, with melting temperatures up to 120°C, and many of the gels display thixotropic properties. Even at low concentrations these compounds self-assemble into elongated and very thin fibers, which in turn form a three-dimensional network in the solvent. Infrared studies showed that aggregation is accompanied by the formation of a hydrogen-bonded network between urea moieties, and a single-crystal X-ray structure of one of the compounds showed that in crystals the molecules assemble into one-dimensional chains, which are stabilized by the formation of eight hydrogen bonds between the urea groups and adjacent molecules. The molecular arrangement in gels is most likely very similar to that in the crystal, but the complete elucidation of the molecular arrangement in gels is complicated because aggregation of these compounds is prone to polymorphism. It is concluded that the very efficient aggregation of these molecules and the elongated shape of the fibers most likely arise from the highly anisotropic hydrogen-bonding properties of these molecules, which is due to the presence of two coplanar oriented urea moieties in a single molecule. Since the bis-urea compounds presented in this paper are very easy to synthesize and many structural variations are possible without loss of the gelation ability, they are excellent building blocks for the construction of functional gels.
- Van Esch, Jan,Schoonbeek, Franck,De Loos, Maaike,Kooijman, Huub,Spek, Anthony L.,Kellogg, Richard M.,Feringa, Ben L.
-
p. 937 - 950
(2007/10/03)
-
- New structures able to prevent the inhibition by hydroxyl radicals of glutamate transport in cultured astrocytes
-
4,5,6,7-Tetrahydro-benzothiophen-7-ylamines, 4,5,6,7-tetrahydro- benzothiophen-4-ylamines, and 5,6-dihydro-4H-thieno[2,3-b] thiopyran-4- ylamines were designed, synthesized, and tested as OH radical scavengers. Most of them displayed chemical scavenging properties better than or in the same range as salicylic acid. Moreover, some compounds were able to protect in vitro the astroglial glutamate transporters against inhibitory action of radicals promoted by xanthine/xanthine oxidase. Thus, such compounds might be useful for lowering the large amounts of excitotoxic glutamate liberated during acute CNS diseases: they might protect the glutamate reuptake in astrocytes from the inhibitory action due to radicals co-liberated with glutamate.
- Cauquil-Caubere, Isoline,Kamenka, Jean-Marc
-
p. 867 - 877
(2007/10/03)
-
- Intramolecular Cycloaddition of Isomuenchnone Dipoles to Heteroaromatic ?-Systems
-
A series of furanyl-, thienyl-, and indolo-substituted diazo imides were prepared by treating the appropriate amides with diketene to give the N-acetoacylated imides.Exposure of the imides to standard diazo transfer conditions afforded the desired diazo imides.Treatment of these diazo imides bearing tethered heterocyclic rings with rhodium(II) acetate affords transient isomuenchnone dipoles.The mesoionic dipoles are formed by cyclization of the rhodium carbenoid onto the neighboring amide carbonyl oxygen atom.The scope and limitations of the intramolecular 1,3-dipolar cycloaddition of the isomuenchnones across a tethered furan and thiophene ring were studied.The facility of the internal cycloaddition is influenced by the length and nature of the tether connecting the dipole and dipolarophile functionalities.The reaction is critically dependent on conformational factors in the transition state.In addition, the first examples of intramolecular cycloaddition of isomuenchnones to indole dipolarophiles are reported.Cycloadditions of this type generate highly functionalized polyheterocyclic systems with complete relative stereocontrol at the newly formed stereocenters.
- Padwa, Albert,Hertzog, Donald L.,Nadler, William R.
-
p. 7072 - 7084
(2007/10/02)
-
- NEW SYNTHESIS OF 1-TRIACONTANOL
-
Succinic anhydride and behenic acid have been used to attach C4 and C22 carbon chains on to 2 and 5 positions of thiophene through two alternate acylation sequences.Raney nickel desulphurization to the 2,5-disubstituted thiophene yielded triacontanoic acid esters which on LAH reduction gave 1-triacontanol.
- Bhalerao, U. T.,Rao, Jagadishwar S.,Tilak, B. D.
-
p. 5439 - 5440
(2007/10/02)
-
- The Synthesis of Thiophenium and Oxazolium Salts from Diazoketones
-
4-Diazoacetylthianthren with perchloric acid in acetonitrile gave 2-oxo-1,2-dihydrothieno-thianthrenium perchlorate which gave the corresponding enol ether with diazomethane.This ether was compared with 3-methoxy-1-methylbenzothiophenium perchlorate, prepared from 3-methoxythiophen, and which was much more stable to solvolysis than the demethoxy-analogue.In contrast to the 4-diazoacetylthianthren, 7-diazoacetyl-2-methylbenzothiophen with acetonitrile and perchloric acid cyclized in an alternative mode to give a new synthesis of 2-methyl-4-substituted oxazolium perchlorates.
- Acheson, R. Morrin,Cooper, Martin W.
-
p. 1185 - 1193
(2007/10/02)
-