VERBINDUNGEN MIT SELEKTIVER WIRKUNG FUER RETINOID X REZEPTOREN, UND MITTEL FUER STEUERUNG FUER DURCH RETINOID X REZEPTOREN BEDINGTE PROZESSE

ANSAMYCINE WITH IMPROVED PHARMAKOLOGI AND BIOLOGICAL CHARACTERISTICS

MODULATORS OF MAS-RELATED G-PROTEIN RECEPTOR X4 AND RELATED PRODUCTS AND METHODS

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I): (I) or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein n, x, A, Q1, Q2, Z, R, R1, R2, R3, R4 and R5 are as defined herein. Pharmaceutical compositions containing such compounds, as well as to compounds themselves, are also provided.

ROLLING-ELEMENT BEARING ASSEMBLY

A rolling-element bearing assembly includes a rolling-element bearing and an oil conditioning system for conditioning oil used to lubricate the bearing. The bearing has an inner ring and an outer ring and a plurality of rolling elements rotatably disposed between the inner ring and the outer ring. The bearing includes openings for discharging oil from the bearing and for introducing oil into the bearing, and the openings are connected to the oil conditioning system. A raceway of the inner ring and/or a raceway of the outer ring is coated with a first coating, and the rolling elements are at least partially coated with a second coating that is different from the first coating. 1. A rolling-element bearing assembly comprising:a rolling-element bearing having an inner ring and an outer ring and a plurality of rolling elements rotatably disposed between the inner ring and the outer ring, the rolling elements being configured to be lubricated with an oil, andan oil conditioning system,wherein the rolling-element bearing includes openings for discharging oil from the rolling-element bearing and introducing oil into the rolling-element bearing,wherein the openings are connected to the oil conditioning system,wherein a raceway of the inner ring and/or a raceway of the outer ring is coated with a first coating and the rolling elements are at least partially coated with a second coating, andwherein the first coating is different from the second coating.2. The rolling-element bearing assembly according to claim 1 ,wherein the openings for introducing oil into the rolling-element bearing are configured as inlet bores on the outer ring and the openings for discharging oil from the rolling-element bearing are configured as outlet bores on the outer ring, andwherein the inlet bores and the outlet bores are axially offset with respect to each other.3. The rolling-element bearing assembly according to claim 1 ,wherein the first coating or the second coating is a phosphate coating.4. ...

Mitteln zur Modulierung von Verfahren durch Retinoid Rezeptoren und dafür nützliche Verbindungen.

Photon multiplier film

There is provided a ternary photon multiplier film. The photon multiplier film comprises an organic semiconductor material capable of multiple exciton generation and a luminescent material in a host material, wherein the bandgap of the luminescent material is selected such that the triplet excitons formed as a result from the multiple exciton generation in the organic semiconductor can be energy transferred into the luminescent material.

MITTELN ZUR MODULIERUNG VON VERFAHREN DURCH RETINOID REZEPTOREN UND DAFÜR NÜTZLICHE VERBINDUNGEN

DRUG FORMULATIONS HAVING LONG AND MEDIUM CHAIN TRIGLYCERIDES

Ansamycin formulations and methods for producing and using same

Leadframe, gekapseltes Package mit gestanzter Leitung und gesägten Seitenflanken, und entsprechendes Herstellungsverfahren

Package (100), das einen Träger (102), eine elektronische Komponente (104) auf dem Träger (102), eine Verkapselung (106), die mindestens einen Teil des Trägers (102) und der elektronischen Komponente (104) verkapselt, und mindestens eine Leitung (108) aufweist, die sich über die Verkapselung (106) hinaus erstreckt und eine gestanzte Oberfläche (130) aufweist, wobei mindestens ein Teil mindestens einer Seitenflanke (110) der Verkapselung (106) eine gesägte Textur (281) aufweist.

Modulators of Mas-related G-protein receptor X4 and related products and methods

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I): (I) or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein ...

Wälzlageranordnung

Offenbart wird eine Wälzlageranordnung (1) mit einem Wälzlager (2), welches einen Innenring (3) und einen Außenring (4) aufweist, zwischen denen Wälzkörper (6) rotierbar angeordnet sind, wobei die Wälzkörper (6) mit Öl schmierbar sind, und mit einem Ölaufbereitungssystem (36), wobei das Wälzlager (2) Öffnungen (42, 44, 46) zum Abführen von Öl aus dem Wälzlager (2) und Einführen von Öl in das Wälzlager (2) aufweist, wobei die Öffnungen (42, 44, 46) mit dem Ölaufbereitungssystem (36) verbunden sind, wobei eine Lauffläche (8) des Innenrings (3) und/oder eine Lauffläche (10) des Außenrings (4) zumindest teilweise mit einer ersten Beschichtung beschichtet ist und wobei die Wälzkörper (6) zumindest teilweise mit einer zweiten Beschichtung beschichtet sind, wobei die erste Beschichtung und die zweite Beschichtung unterschiedlich zueinander sind, nämlich vorzugsweise Phosphatierung und Brünierung.

Insulating hood for food product transporting system

The insulating hood (1) can be clamped over a pallet on rollers, and consists of a roof (7) and four side walls (5,6) made of a flexible material resistant to heat and cold. The pallet is loaded and unloaded through an aperture (8) in one side wall. The insulating hood can be clamped over the side walls of a pallet on rollers, to convert the pallet into a thermally insulated transporting device. An extra roof (15) can be fitted to make side parts (21) of the pallet more rigid. A separate flow (11) is inserted to insulate the floor of the pallet.

SELEKTIVITAET FUER RETINOID X REZEPTOREN ENTHALTENDE VERBINDUNGEN

Flächenheizeinrichtung zum Aufheizen von Wasser in einem Laugenbehälter, Waschmaschine und Verfahren zum Herstellen einer Flächenheizeinrichtung

Die Erfindung betrifft eine Flächenheizeinrichtung (6) zum Aufheizen von Wasser in einem Laugenbehälter (4) einer Waschmaschine (1), mit einer flachen Trägerplatte (7) zum Anbringen an dem Laugenbehälter (4), und mit einem als Leiterbahn (13) ausgebildeten Heizleiter (12) zum Erzeugen von Wärme, wobei die Wärme durch die Trägerplatte (7) hindurch an das Wasser abgebbar ist, und wobei zwischen dem Heizleiter (12) und der Trägerplatte (7) eine Zwischenschicht (10) mit einer gegenüber der Trägerplatte (7) größeren Wärmeleitfähigkeit angeordnet ist und die Zwischenschicht (10) zur gleichmäßigen Verteilung der Wärme ausgebildet ist. The invention relates to a Flächenheizeinrichtung (6) for heating water in a tub (4) of a washing machine (1), with a flat support plate (7) for attachment to the tub (4), and formed as a conductor (13) heating conductor (12) for generating heat, wherein the heat through the support plate (7) through the water is deliverable, and wherein between the heating conductor (12) and the support plate (7) has an intermediate layer (10) with respect to the support plate (7 ) is arranged greater thermal conductivity and the intermediate layer (10) is designed for uniform distribution of heat.

ANSAMYCIN FORMULATIONS AND METHODS FOR PRODUCING AND USING SAME

CYTOTOXINS AND DIAGNOSTIC IMAGING AGENTS COMPRISING HSP90 LIGANDS

MITTELN ZUR MODULIERUNG VON VERFAHREN DURCH RETINOID REZEPTOREN UND DAFÜR NÜTZLICHE VERBINDUNGEN

Verwendung von mindestens einer Verbindung gemäß einer der folgenden Strukturen A und I bis VII: worin die ungesättigte Bindung zwischen den Kohlenstoffatomen C9 und C10 eine cis-Konfiguration hat, und eine oder beide ungesättigte Stellen zwischen den Kohlenstoffatomen C11 bis C14 wahlweise eine cis-Konfiguration hat; „Ring” ist eine cyclische Einheit, wahlweise mit einem oder mehreren Substituenten daran; Z ist ausgewählt aus Carboxyl (-COOH), Hydroxyalkyl [-(CR'2)n-OH, worin R' jeweils unabhängig ausgewählt ist aus Wasserstoff oder C1-C4-Alkyl und n in den Bereich von 1 bis 4 fällt], Thioalkyl [-(CR'2)n-SH, worin R' und n wie oben definiert sind], Hydroxyalkylphosphat [-(CR'2)n-OP(OM)3, worin R' und n wie oben definiert sind, und M ist Wasserstoff, C1-C4-Alkyl oder eine kationische Spezies wie Na+, Li+, K+], Alkylether einer Hydroxyalkylgruppe [-(CR'2)n-OR', worin R' und n wie oben definiert sind], Alkylthioether einer Thioalkylgruppe [-(CR'2)n-SR', worin R' und n wie oben definiert sind ...

Drug formulations having long and medium chain triglycerides

MITTELN ZUR MODULIERUNG VON VERFAHREN DURCH RETINOID REZEPTOREN UND DAFÜR NÜTZLICHE VERBINDUNGEN

µLED CHIP ARCHITEKTUR BASIEREND AUF NANOSTRUKTURIERTEN PEROWSKIT-KONVERTERMATERIALIEN

Die vorliegende Erfindung bezieht sich auf ein Verfahren zur Herstellung eines optoelektronischen Halbleiterbauelements, umfassend:- Bereitstellen eines optoelektronischen Halbleiterchips (1) umfassend:mindestens eine lichtemittierende Schicht (4),mindestens eine Kavität (3), und- Einbringen mindestens einer Vorstufe eines Konversionselements, wobei das mindestens eine Konversionselement (6, 6') eine Perowskit-basierte ABX- oder ABB'X-Struktur umfasst.Ferner ist Gegenstand der Erfindung ein optoelektronisches Halbleiterbauelement und die Verwendung eines optoelektronischen Halbleiterbauelements.

MINIMIERUNG VON STOKESVERLUSTEN DURCH PHOTONMULTIPLIKATIONSPROZESSE FÜR IR-ANWENDUNGEN

Gegenstand der Erfindung ist ein lichtemittierendes Bauelement (1) umfassend:- mindestens ein Konversionselement (3) umfassend:- mindestens ein erstes Material ausgewählt aus der Gruppe bestehend aus Polyazen, Rubren und Derivaten davon;- mindestens ein zweites Material, wobei es sich bei dem zweiten Material um einen Quantenpunkt handelt, und- mindestens eine Lichtquelle (2), wobei die mindestens eine Lichtquelle (2) mindestens ein Photon im Bereich von 3,5 eV bis 2,5 eV, bevorzugt im Bereich von 3,0 eV bis 2,55 eV, emittiert.Ferner ist Gegenstand der vorliegenden Erfindung die Verwendung eines erfindungsgemäßen lichtemittierenden Bauelements (1).

SELEKTIVITAET FUER RETINOID X REZEPTOREN ENTHALTENDE VERBINDUNGEN

Haushaltsgerät zur Pflege von Wäschestücken und Verfahren zum Erfassen einer Bewegung eines Laugenbehälters

Die Erfindung betrifft ein Haushaltsgerät 1 zur Pflege von Wäschestücken 4, mit einem in einem Gerätegehäuse 6 des Haushaltsgeräts 1 angeordneten Laugenbehälter 2, in welchem eine Wäschetrommel 3 zur Aufnahme der Wäschestücke 4 drehbar gelagert ist, und mit einer Sensoreinrichtung 17 zum Erfassen einer Bewegung des Laugenbehälters 2 relativ zum Gerätegehäuse 6, wobei die Sensoreinrichtung 17 zumindest einen kapazitiven Sensor mit einer sich infolge der Bewegung ändernden elektrischen Kapazität aufweist und zum Erfassen der Bewegung abhängig von der elektrischen Kapazität des kapazitiven Sensors ausgebildet ist, wobei der kapazitive Sensor als dielektrischer Elastomer-Sensor 18, 18a, 18b ausgebildet ist.

Drucksensor für ein Haushaltsgerät

Drucksensor (1) für ein Haushaltsgerät (W), aufweisend einen Fluidaufnahmeraum (R), welcher zumindest teilweise von einem beweglichen Wandelement (7) begrenzt ist, welches Wandelement (7) sich in Abhängigkeit von einem Druck eines in dem Fluidaufnahmeraum (R) befindlichen Fluids (F) nach Außen wölbt, ein elastisch verformbares Rückstellelement (11), welches das Wandelement (7) in Richtung des Fluidaufnahmeraums (R) drückt, und einen außenseitig des Wandelements (7) angeordneten Schwingkreis (11, 13) mit einer Induktivität, wobei ein Induktivitätswert von einem Maß einer Wölbung des Wandelements (7) abhängt, wobei das elastische Rückstellelement (11) die Induktivität darstellt, und der Induktivitätswert des elastischen Rückstellelements (11) mit seinem Deformationsmaß korreliert.

Wäschepflegegerät mit einer Beleuchtungseinrichtung

Die vorliegende Erfindung betrifft ein Wäschepflegegerät (100) mit einer Beleuchtungseinrichtung (113) zum Beleuchten des Wäschepflegegeräts (100). Die Beleuchtungseinrichtung (113) weist eine Lichtquelle (115) auf, welche ausgebildet ist, Licht abzustrahlen, um das Wäschepflegegerät (100) zu beleuchten. Die Beleuchtungseinrichtung (113) weist ein Wärmeabführelement (117) auf, welches aus einem thermisch leitfähigen Kunststoff geformt ist, wobei der thermisch leitfähige Kunststoff ausgebildet ist, durch die Lichtquelle (115) freigesetzte Wärme abzuführen, um die Lichtquelle (115) zu kühlen.

MITTELN ZUR MODULIERUNG VON VERFAHREN DURCH RETINOID REZEPTOREN UND DAFÜR NÜTZLICHE VERBINDUNGEN.

MODULATORS OF MAS-RELATED G-PROTEIN RECEPTOR X4 AND RELATED PRODUCTS AND METHODS

LICHTEMITTIERENDES BAUELEMENT UND VERWENDUNG EINES LICHTEMITTIERENDEN BAUELEMENTS ZUR MINIMIERUNG VON STOKESVERLUSTEN DURCH PHOTONMULTIPLIKATIONSPROZESSE FÜR IR-ANWENDUNGEN

Lichtemittierendes Bauelement (1) umfassend:- mindestens ein Konversionselement (3) umfassend:- mindestens ein erstes Material ausgewählt aus der Gruppe bestehend aus Tetracen, Pentacen und Derivaten davon;- mindestens ein zweites Material, wobei es sich bei dem zweiten Material um einen Quantenpunkt handelt, und- mindestens eine Lichtquelle (2), wobei die mindestens eine Lichtquelle (2) mindestens ein Photon im Bereich von 3,5 eV bis 2,5 eV, bevorzugt im Bereich von 3,0 eV bis 2,55 eV, emittiert.

Retinoid-x Rezeptor selektive Verbindungen

MODULATORS OF MAS-RELATED G-PROTEIN RECEPTOR X4 AND RELATED PRODUCTS AND METHODS

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I). 3. The method of claim 2 , wherein the MRGPR X4 dependent condition is a condition that is caused by the activation of MRGPR X4 by a bile acid or analog thereof.4. The method of wherein the MRGPR X4 dependent condition is an itch associated condition claim 2 , a pain associated condition claim 2 , or an autoimmune disorder.5rubra. The method of wherein the itch associated condition is chronic itch claim 4 , cholestatic pruritus claim 4 , contact dermatitis claim 4 , allergic blepharitis claim 4 , anemia claim 4 , atopic dermatitis claim 4 , bullous pemphigoid claim 4 , candidiasis claim 4 , chicken pox claim 4 , cholestasis claim 4 , end-stage renal failure claim 4 , hemodialysis claim 4 , contact dermatitis claim 4 , dermatitis herpetiformis claim 4 , diabetes claim 4 , drug allergy claim 4 , dry skin claim 4 , dyshidrotic dermatitis claim 4 , ectopic eczema claim 4 , eczema claim 4 , erythrasma claim 4 , folliculitis claim 4 , fungal skin infection claim 4 , hemorrhoids claim 4 , herpes claim 4 , HIV infection claim 4 , Hodgkin's disease claim 4 , hyperthyroidism claim 4 , iron deficiency anemia claim 4 , kidney disease claim 4 , leukemia claim 4 , liver disease claim 4 , lymphoma claim 4 , malignancy claim 4 , multiple myeloma claim 4 , neurodermatitis claim 4 , onchocerciasis claim 4 , Paget's disease claim 4 , pediculosis claim 4 , polycythemia vera claim 4 , pruritus ani claim 4 , pseudorabies claim 4 , psoriasis claim 4 , rectal prolapse claim 4 , scabies claim 4 , schistosomiasis claim 4 , scleroderma claim 4 , severe stress claim 4 , stasia dermatitis claim 4 , swimmer's itch claim 4 , thyroid disease claim 4 , tinea cruris claim 4 , uremic pruritus claim 4 , or urticaria.6. The ...

Haushaltsgerät mit Spülwasserbehälter

Die vorliegende Erfindung betrifft ein Haushaltsgerät (100) mit einem Spülwasserbehälter (101) zum Aufnehmen von Spülwasser (103) und einem Laugenbehälter (105) zum Aufnehmen einer Waschlauge (107), bei dem das Haushaltsgerät (100) einen Thermogenerator (109) zum Übertragen einer Wärmemenge vom Spülwasser (103) auf die Waschlauge (107) umfasst.

Mitteln zur Modulierung von Verfahren durch retinoid Rezeptoren und dafuer nuetzliche Verbindungen

VERBINDUNGEN MIT SELEKTIVER WIRKUNG FUER RETINOID X REZEPTOREN, UND MITTEL FUER STEUERUNG FUER DURCH RETINOID X REZEPTOREN BEDINGTE PROZESSE

Rolling-element bearing assembly

A rolling-element bearing assembly includes a rolling-element bearing and an oil conditioning system for conditioning oil used to lubricate the bearing. The bearing has an inner ring and an outer ring and a plurality of rolling elements rotatably disposed between the inner ring and the outer ring. The bearing includes openings for discharging oil from the bearing and for introducing oil into the bearing, and the openings are connected to the oil conditioning system. A raceway of the inner ring and/or a raceway of the outer ring is coated with a first coating, and the rolling elements are at least partially coated with a second coating that is different from the first coating.

PHOTON MULTIPLIER FILM

There is provided a ternary photon multiplier film. The photon multiplier film comprises an organic semiconductor material capable of multiple exciton generation and a luminescent material in a host material, wherein the bandgap of the luminescent material is selected such that the triplet excitons formed as a result from the multiple exciton generation in the organic semiconductor can be energy transferred into the luminescent material. 1: A photon multiplier film comprising an organic semiconductor material capable of multiple exciton generation and a luminescent material in a host material , wherein the bandgap of the luminescent material is selected such that the triplet excitons formed as a result from the multiple exciton generation in the organic semiconductor can be energy transferred into the luminescent material.2: The photon multiplier film as claimed in claim 1 , wherein the organic semiconductor material and the luminescent material are present in mass concentrations x % and y % claim 1 , wherein x and y are less than the mass concentration z % of the host material claim 1 , such that z>x and z>y.3: The photon multiplier film as claimed in claim 1 , wherein the concentration of the host material by mass is greater than 15%.4: The photon multiplier film as claimed in claim 3 , wherein the concentration of the host material by mass is in the 15-99.7% range.5: The photon multiplier film as claimed in claim 1 , wherein the concentration of the organic semiconductor by mass is <50%.6: The photon multiplier film as claimed in where the concentration of the luminescent material by mass is <50%.7: The photon multiplier film as claimed in claim 1 , wherein the organic semiconductor is selected from a small molecule claim 1 , an oligomer claim 1 , a homopolymer claim 1 , a copolymer claim 1 , a dendrimer or an organometallic complex.8: The photon multiplier film as claimed in claim 1 , wherein the organic semiconductor is a singlet fission material.9: The photon ...

NOVEL GLP-1 RECEPTOR MODULATORS

The invention relates to compounds that modulate the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds are act as modulators or potentiators of GLP-1 receptor on their own, or with receptor ligands including GLP-1 peptides GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 2. The compound of wherein Yand Yare null claim 1 , Z is —C(O)— and A is a 5- or 6-membered heteroaryl group.4. The compound of wherein Yand Yare null claim 1 , Z is —C(O)— and A is a 5- or 6-membered non-aromatic heterocycyl group.6. The compound of wherein Yand Yare null claim 1 , Z is —C(O)— and C is aryl.8. The compound of wherein Yand Yare null claim 1 , Z is —C(O)— and C is heterocyclyl.10. The compound of wherein Yand Yare null claim 1 , Z is —C(O)— and B is aryl or arylalkyl.12. The compound of wherein Yand Yare null claim 1 , Z is —C(O)— and B is heterocyclyl or heterocyclylalkyl.14. The compound of wherein Yand Yare null claim 1 , Z is —S(O)—.16. The compound of wherein where Yis null claim 1 , Yis —O— and Z is —C(O)—.18. The compound of wherein where Yis NH claim 1 , Yis null and Z is —C(O)—.20. A pharmaceutical composition comprising a compound of together with at least one pharmaceutically acceptable carrier claim 1 , diluent or excipient.21. A pharmaceutical combination comprising the compound of and a second medicament.22. The pharmaceutical combination of wherein the second medicament is an agonist or modulator for glucagon receptor claim 21 , GIP receptor claim 21 , GLP-2 receptor claim 21 , or PTH receptor claim 21 , or glucagon-like peptide 1 (GLP-1) receptor.23. The pharmaceutical combination of wherein the second medicament is exenatide claim 21 , liraglutide claim 21 , taspoglutide claim 21 , albiglutide claim 21 , or ...

Sphingosine 1 phosphate receptor modulators and methods of chiral synthesis

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

NOVEL GLP-1 RECEPTOR STABILIZERS AND MODULATORS

Compounds that bind the glucagon-like peptide 1 receptor (GLP-1) receptor are provided including compounds which are modulators of the GLP-1 receptors and compounds which are capable of inducing a stabilizing effect on the receptor for use in structural analyses of the GLP-1 receptor. Methods of synthesis, methods of therapeutic and/or prophylactic use, and methods of use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor of such compounds are provided. 2. The compound of wherein the compound has the structure of Formula I-R or a pharmaceutically acceptable salt claim 1 , ester claim 1 , prodrug claim 1 , homolog claim 1 , hydrate or solvate thereof.3. The compound of wherein the compound has the structure of Formula I-S or a pharmaceutically acceptable salt claim 1 , ester claim 1 , prodrug claim 1 , homolog claim 1 , hydrate or solvate thereof.4. The compound of wherein the compound is substantially enantiomerically pure.5. The compound of wherein Wis -L-(CRR)-L-R.6. The compound of wherein Wis -L-(CRR)—R.7. The compound of wherein one of Lis —O—.8. The compound of wherein one of Lis —C(O)O—.9. The compound of wherein one of Lis —S(O)—.10. The compound of wherein one of Lis —S—.11. The compound of wherein one of Lis —N(R).12. The compound of wherein one of Lis —N(R)—C(O)—N(R)—.13. The compound of wherein one of Lis —N(R)—C(O)—.14. The compound of wherein one of Lis —S(O)—N(R)—.15. The compound of wherein Ris H.16. The compound of wherein one of Lis —O—.17. The compound of wherein both Rand Rare H.18. The compound of wherein one of Rand Ris methyl.19. The compound wherein one of Rand Ris methoxy.20. The compound of wherein in at least one instance Rand Rtaken together with the carbon to which they are attached form a cycloalkyl.21. The compound of wherein Ris alkyl substituted with Rand Ris phenyl.22. The compound of wherein Wis —NHC(O)—(CH)-L-R.23. The compound of wherein Ris H or alkyl.24. The compound of wherein Ris cycloalkyl claim ...

SELECTIVE HETEROCYCLIC SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated. 161-. (canceled)62. A method for the synthesis of a compound comprising an indane moiety having a chiral carbon in the five-membered ring of the indane moiety where the compound is enantiomerically enriched with respect to the chiral carbon , the method comprising the steps of(i) providing a compound comprising an indane moiety where the ring carbon of the five-membered ring of the indane moiety where chiral substitution is desired is oxo substituted at such carbon, and wherein a carbon of the phenyl ring is halo substituted;{'sub': 2', '2-6', '3-8, '(ii) reacting such compound with a chiral reagent selected from the group consisting of a Corey Bakshita Shibata-oxazaborolidine and a chiral sulfinamide of the form RS(═O)NHwhere R is selected from the group consisting of t-butyl, branched Calkyl and Ccycloalkyl; and'}(iii) forming the chiral center at the indane moiety carbon previously bound to the oxo group by either reacting such compound with a suitable reducing agent along with the chiral reagent in step (ii) or reacting the result of the reaction of such compound with a suitable reducing agent.63. The method of wherein the chiral reagent is the Corey Bakshita Shibata-oxazaborolidine.64. The method of wherein the chiral reagent is (R)-(−)-(2)-methyl-CBS-oxazaborolidine or (S)-(−)-(2)-methyl-CBS-oxazaborolidine.67. The method of wherein the protecting agent is TBSCl.69. The method of wherein the chiral reagent is RS(═O)NHand the compound comprising an ...

NOVEL GLP-1 RECEPTOR MODULATORS

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 815-. (canceled)2024-. (canceled)27. (canceled)30. (canceled)3347-. (canceled)50. (canceled)61. (canceled)6466-. (canceled)69. (canceled)7280-. (canceled)83. (canceled)86. (canceled)95. (canceled)98. (canceled)101. (canceled)104. (canceled)107. (canceled)108. A pharmaceutical composition comprising a compound of together with at least one pharmaceutically acceptable carrier claim 1 , diluent or excipient.109115-. (canceled)116. A method of activation claim 108 , potentiation claim 108 , modulation or agonism of a glucagon-like peptide 1 receptor comprising contacting the receptor with a pharmaceutical composition of .117. A method of treatment of a malcondition in a patient for which activation claim 1 , potentiation claim 1 , modulation or agonism of a glucagon-like peptide 1 receptor is medically indicated claim 1 , comprising administering an effective amount of the compound of to the patient at a frequency and for a duration of time sufficient to provide a beneficial effect to the patient.118. The method of wherein the malcondition is type I diabetes claim 117 , type II diabetes claim 117 , gestational diabetes claim 117 , obesity claim 117 , excessive appetite claim 117 , insufficient satiety or metabolic disorder.119. The method of wherein the malcondition is type II diabetes. The invention relates to compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. The present ...

Novel glp-1 receptor modulators

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “ ” represents either or both the R and S form of the compound): where A, B, C, Y 1 , Y 2 , Z, R 1 , R 2 , R 3 , R 4 , R 5 , W 1 , n, p and q are as defined herein.

NOVEL GLP-1 RECEPTOR MODULATORS

The invention relates to compounds that modulate the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds are act as modulators or potentiators of GLP-1 receptor on their own, or with receptor ligands including GLP-1 peptides GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 124-. (canceled)28. The method of wherein the malcondition is type I diabetes claim 27 , type II diabetes claim 27 , gestational diabetes claim 27 , obesity claim 27 , excessive appetite claim 27 , insufficient satiety or metabolic disorder.29. The method of wherein the malcondition is type I diabetes or type II diabetes.3029. The method of any one of - wherein A is a 5- or 6-membered heteroaryl group.3229. The method of any one of - wherein C is aryl.3429. The method of any one of - wherein B is heterocyclyl.3629. The method of any one of - wherein the compound is administered in combination with a second medicament.37. The method of wherein the second medicament is an agonist or modulator for glucagon receptor claim 36 , GIP receptor claim 36 , GLP-2 receptor claim 36 , or PTH receptor claim 36 , or glucagon-like peptide 1 (GLP-1) receptor.38. The method of wherein the second medicament is exenatide claim 36 , liraglutide claim 36 , taspoglutide claim 36 , albiglutide claim 36 , or lixisenatide.39. The method of wherein the second medicament is a DPPIV inhibitor. The invention relates to compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. The present invention is directed to compounds adapted to act as modulators or potentiators of GLP-1 receptor, including peptides GLP-1(7-36) and GLP-1(9-36), as well as peptide-based therapies such as exenatide and ...

NOVEL GLP-1 RECEPTOR MODULATORS

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36), GLP-1(9-36), and oxyntomodulin, or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 17. The compound of wherein B is pyrimidinyl.18. The compound of wherein B is pyrazolyl.19. The compound of wherein B is pyridinyl.20. The compound of wherein B is indolyl.21. The compound of wherein C is nonaromatic carbocyclyl.22. The compound of wherein nonaromatic carbocyclyl is cycloalklyl.23. The compound of wherein nonaromatic carbocyclyl is cycloalkenyl.27. The compound of wherein Ris H.28. The compound of wherein Ris H.29. The compound of wherein q is one.30. The compound of wherein Ris alkyl.31. The compound of wherein p is one.32. The compound of wherein Ris alkyl.33. The compound of wherein alkyl is a straight or branched alkyl.34. The compound of wherein alkyl is cycloalky.3938. The compound of any one of - wherein each alkyl is independently a C-Cstraight or branched alkyl.40. The compound of wherein each alkyl is independently methyl claim 39 , ethyl claim 39 , n-propyl claim 39 , iso-propyl claim 39 , n-butyl claim 39 , iso-butyl claim 39 , sec-butyl or tert-butyl.4138. The compound of any one of - wherein Ris —N(R)(CRR)COOR.42. The compound of wherein m is 2 claim 41 , Ris hydrogen claim 41 , each occurrence of Rand Rare hydrogen claim 41 , and Ris hydrogen.43. The compound of wherein m is 1 claim 41 , R claim 41 , Rand Rare hydrogen claim 41 , and Ris as defined in .44. The compound of wherein m is 2 claim 41 , a single Ris hydrogen and the other Ris as defined in claim 41 , each occurrence of Ris hydrogen claim 41 , and Rand Rare ...

MODULATORS OF MAS-RELATED G-PROTEIN RECEPTOR X2 AND RELATED PRODUCTS AND METHODS

Methods are provided for modulating MRGPRX2 or a MRGPRX2 ortholog generally, or for treating a MRGPRX2 or a MRGPRX2 ortholog dependent condition more specifically, by contacting the MRGPRX2 or the MRGPRX2 ortholog by administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I): 3. The method of claim 2 , wherein the MRGPRX2 or the MRGPRX2 ortholog dependent condition is a pseudo-allergic reaction claim 2 , an itch associated condition claim 2 , a pain associated condition claim 2 , or an inflammatory or autoimmune disorder.4. The method of claim 3 , wherein the itch associated condition is chronic itch; contact dermatitis; Allergic blepharitis; Anemia; Atopic dermatitis; Bullous pemphigoid; Candidiasis; Chicken pox; end-stage renal failure; hemodialysis; Chronic urticaria; Contact dermatitis claim 3 , Atopic Dermatitis; Dermatitis herpetiformis; Diabetes; Drug allergy claim 3 , Dry skin; Dyshidrotic dermatitis; Ectopic eczema; Eosinophilic fasciitis; Epidermolysis bullosa; Erythrasma; Food allergy; Folliculitis; Fungal skin infection; Hemorrhoids; Herpes; HIV infection; Hodgkin's disease; Hyperthyroidism; Iodinated contrast dye allergy; Iron deficiency anemia; Kidney disease; Leukemia claim 3 , porphyrias; Lymphoma; Malignancy; Mastocystosis; Multiple myeloma; Neurodermatitis; Onchocerciasis; Paget's disease; Pediculosis; Polycythemia rubra vera; Prurigo nodularis; Lichen Planus; Lichen Sclerosis; Pruritus ani; Pseudorabies; Psoriasis; Rectal prolapse; Sarcoidosis granulomas; Scabies; Schistosomiasis; Scleroderma claim 3 , Severe stress claim 3 , Stasia dermatitis; Swimmer's itch; Thyroid disease; Tinea cruris; Rosacea; Cutaneous amyloidosis; Scleroderma; Acne; wound healing; burn healing; ocular itch; or Urticaria.5. The method of claim 4 , wherein the itch associated condition is urticaria claim 4 , pruritus claim 4 , atopic dermatitis claim 4 , dry skin claim 4 , psoriasis claim 4 , contact dermatitis claim 4 , ...

Selective sphingosine 1 phosphate receptor modulators and combination therapy therewith

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided, including compounds which modulate subtype 1 of the S1P receptor, and methods of their therapeutic and/or prophylactic use in combination with at least one other medicament adapted for treatment of a malcondition for which activation of S1P 1 is medically indicated, such as multiple sclerosis.

Leadframe, Encapsulated Package with Punched Lead and Sawn Side Flanks, and Corresponding Manufacturing Method

A package includes a carrier, an electronic component on the carrier, an encapsulant encapsulating at least part of the carrier and the electronic component, and at least one lead extending beyond the encapsulant and having a punched surface, wherein at least part of at least one side flank of the encapsulant has a sawn texture. 1. A package , comprising:a carrier;an electronic component on the carrier;an encapsulant encapsulating at least part of the carrier and the electronic component; andat least one lead extending beyond the encapsulant and having a punched surface,wherein at least part of at least one side flank of the encapsulant has a sawn texture.2. The package according to claim 1 , wherein the at least one side flank is defined by the encapsulant and a tie bar connected to the carrier claim 1 , and comprises at least one of the following features:a ratio between a surface area of an exposed tie bar at a respective side flank and an entire surface area of the respective side flank is less than 10%, in particular less than 5%, more particularly less than 3%; andthe tie bar has a thicker portion in an interior of the encapsulant and has a thinner portion at the respective side flank.3. The package according to claim 1 , wherein the encapsulant has at least one slanted side wall at which the at least one lead extends beyond the encapsulant.4. The package according to claim 1 , wherein the at least one side flank with the sawn texture has a vertical side wall.5. The package according to claim 1 , wherein the at least one lead is at least partially covered with a plating layer.6. The package according to claim 1 , wherein at least one other side flank of the encapsulant has a molded texture.7. The package according to claim 1 , wherein the encapsulant has at least one recess in at least one of the at least one side flank having the sawn texture.8. The package according to claim 1 , comprising a clip electrically connected to an upper main surface of the ...

NOVEL GLP-1 RECEPTOR MODULATORS

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1 (7-36) and GLP-1 (9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 2106-. (canceled)107. The compound of claim 1 , wherein the compound has the structure of any one of the compounds of Table 1 or a pharmaceutically acceptable isomer claim 1 , enantiomer claim 1 , racemate claim 1 , salt claim 1 , ester claim 1 , prodrug claim 1 , hydrate or solvate thereof.108. A pharmaceutical composition comprising a compound of together with at least one pharmaceutically acceptable carrier claim 1 , diluent or excipient.109. A pharmaceutical combination comprising the compound of and a second medicament.110. The pharmaceutical combination of wherein the second medicament is an agonist or modulator for glucagon receptor claim 109 , GIP receptor claim 109 , GLP-2 receptor claim 109 , or PTH receptor claim 109 , or glucagon-like peptide 1 (GLP-1) receptor.111. The pharmaceutical combination of wherein the second medicament is exenatide claim 109 , liraglutide claim 109 , taspoglutide claim 109 , albiglutide claim 109 , or lixisenatide.112. The pharmaceutical combination of wherein the second medicament is a DPPIV inhibitor.113. The pharmaceutical combination of wherein the second medicament is sitagliptin.114. The pharmaceutical combination of wherein the second medicament is a biguanide claim 109 , a sulfonylurea claim 109 , a meglitinide claim 109 , a thiazolidinedione claim 109 , an α-glucosidase inhibitor claim 109 , a bile acid sequestrant claim 109 , and/or a dopamine-2 agonist.115. The pharmaceutical combination of wherein the second ...

NOVEL GLP-1 RECEPTOR MODULATORS

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36), GLP-1(9-36), and oxyntomodulin, or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 178-. (canceled)83. The method of wherein B is pyrimidinyl claim 79 , pyrazolyl claim 79 , pyridinyl or indolyl.84. The method of wherein C is nonaromatic carbocyclyl.85. The method of wherein nonaromatic carbocyclyl is cycloalkyl.86. The method of wherein nonaromatic carbocyclyl is cycloalkenyl.89. The method of wherein Ris H.90. The method of wherein Ris H.91. The method of wherein q is one.92. The method of wherein Ris alkyl.93. The method of wherein p is one.94. The method of wherein Ris alkyl.95. The method of wherein alkyl is a straight or branched alkyl.96. The method of wherein alkyl is cycloalky.111. The method of any one of or - claim 94 , wherein the condition is non-alcoholic fatty liver disease (NAFLD).112. The method of any one of or - claim 94 , wherein the condition is non-alcoholic steatohepatitis (NASH). The invention relates to compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, and methods of their therapeutic and/or prophylactic use. The present invention is directed to compounds adapted to act as modulators of the GLP-1 receptor, and potentiators of incretin peptides, such as GLP-1(7-36), GLP-1(9-36), and oxyntomodulin, as well as peptide-based therapies such as exenatide and liraglutide.Glucagon-like peptide 1 receptor (GLP-1R) belongs to Family B1 of the seven-transmembrane G protein-coupled receptors, and its natural agonist ligand is the peptide hormone glucagon-like peptide-1 (GLP-1). ...

NOVEL GLP-1 RECEPTOR MODULATORS

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 514-. (canceled)1831-. (canceled)3641-. (canceled)4350-. (canceled)5259-. (canceled)83. The compound of claim 1 , wherein the compound has the structure of any one of compounds 1 through 1553 of Table 1 or a pharmaceutically acceptable isomer claim 1 , enantiomer claim 1 , racemate claim 1 , salt claim 1 , ester claim 1 , prodrug claim 1 , hydrate or solvate thereof.84. A pharmaceutical composition comprising a compound of together with at least one pharmaceutically acceptable carrier claim 1 , diluent or excipient.85. A pharmaceutical combination comprising the compound of and a second medicament.8692-. (canceled)93. A method of activation claim 1 , potentiation claim 1 , modulation or agonism of a glucagon-like peptide 1 receptor comprising contacting the receptor with an effective amount of a compound of .94. A method of potentiating a glucagon-like peptide 1 receptor comprising contacting the receptor with a compound of in the presense of GLP-1(7-36) claim 1 , GLP-1(9-36) and/or oxyntomodulin.95. A method of treatment of a malcondition in a patient for which activation claim 1 , potentiation claim 1 , modulation or agonism of a glucagon-like peptide 1 receptor is medically indicated claim 1 , comprising administering an effective amount of the compound of to the patient at a frequency and for a duration of time sufficient to provide a beneficial effect to the patient.96. The method of wherein the malcondition is type I diabetes claim 95 , type II diabetes claim 95 ...

µLED Chip Architecture Based on Nanostructured Perovskite Converter Materials

A method for producing an optoelectronic semiconductor component and an optoelectronic component are disclosed. In an embodiment a method includes providing an optoelectronic semiconductor chip comprising at least one light-emitting layer and at least one cavity and introducing at least one precursor of a conversion element in the at least one cavity, wherein the at least one conversion element comprises a perovskite-based ABXor ABB′Xstructure. 115-. (canceled)16. A method for producing an optoelectronic semiconductor component , the method comprising:providing an optoelectronic semiconductor chip comprising at least one light-emitting layer and at least one cavity; and{'sub': 3', '2', '6, 'introducing at least one precursor of a conversion element in the at least one cavity, wherein the at least one conversion element comprises a perovskite-based ABXor ABB′Xstructure.'}17. The method according to claim 16 , wherein introducing the precursor of the at least one conversion element comprises:introducing a solution of AX into the at least one cavity; and{'sub': 2', '3', '3', '2', '6, 'introducing a solution of BXin case of the ABXstructure or BX and B′Xin case of the ABB′Xstructure into the at least one cavity,'}{'sup': +', '+', '+, 'wherein A is at least one cation selected from the group consisting of methylammonium, formamidinium, K, Rb and Cs,'}{'sup': −', '−', '−', '−, 'wherein X is selected from the group consisting of F, Cl, Br and I,'}{'sup': 2+', '2+', '2+, 'wherein B is a cation selected from the group consisting of Pb, Sn and Ge, and'}{'sub': 2', '6, 'sup': +', '+', '3+, 'wherein, in the case of the ABB′Xstructure, B and B′ is selected from the group Ag, Bi and Bi.'}18. The method according to claim 17 , wherein introducing the precursor of the at least one conversion element further comprises heating the solutions to a temperature in a range between 50° C. and 200° C. claim 17 , inclusive.19. The method according to claim 18 , wherein heating is performed ...

Selective heterocyclic sphingosine 1 phosphate receptor modulators

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

NOVEL GLP-1 RECEPTOR STABILIZERS AND MODULATORS

Compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, methods of their therapeutic and/or prophylactic use, and methods of their use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor are provided. Certain compounds may have activity as modulators or potentiators with respect to glucagon receptor, GIP receptor, GLP-1 and GLP-2 receptors, and PTH receptor on their own or in the presence of receptor ligands such as GIP (1-42), PTH (1-34), Glucagon (1-29), GLP-2 (1-33), GLP-1 (7-36), GLP-1 (9-36), oxyntomodulin and exendin variants. 567-. (canceled)69. The compound of wherein Ris phenyl substituted with one or more substituents selected independently from the group consisting of methyl claim 68 , ethyl claim 68 , isopropyl claim 68 , t-butyl claim 68 , —CF claim 68 , methoxy claim 68 , ethoxy claim 68 , hydroxyl claim 68 , —OCF claim 68 , or halogen claim 68 , methylthio claim 68 , and —SOCH.70. The compound of wherein Ris phenyl substituted with one or more substituents selected independently from the group consisting of methyl claim 69 , methoxy claim 69 , and —CF.7280-. (canceled)83. A pharmaceutical composition comprising a compound of together with at least one pharmaceutically acceptable carrier claim 1 , diluent or excipient.84. A pharmaceutical combination comprising the compound of and a second medicament.8591-. (canceled)92. A method of activation claim 1 , potentiation or agonism of a glucagon-like peptide 1 receptor comprising contacting the receptor with an effective amount of a compound of .94. The method of wherein the subject is a human being.95. A method of treatment of a malcondition in a patient for which activation claim 1 , potentiation or agonism of a glucagon-like peptide 1 receptor is medically indicated claim 1 , comprising administering an effective amount of the compound of to the patient at a frequency and for a duration of time sufficient to provide a beneficial effect to ...

MODULATORS OF MAS-RELATED G-PROTEIN RECEPTOR X4 AND RELATED PRODUCTS AND METHODS

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I): 3. The method of wherein the MRGPR X4 dependent condition is an itch associated condition claim 2 , a pain associated condition claim 2 , or an autoimmune disorder.413-. (canceled)14. The method of claim 2 , wherein the compound has the structure of a compound listed Table A claim 2 , or a pharmaceutically acceptable isomer claim 2 , racemate claim 2 , hydrate claim 2 , solvate claim 2 , isotope claim 2 , or salt thereof.1718-. (canceled)2125-. (canceled)28. (canceled)31. (canceled)33. (canceled)35. (canceled)37. (canceled)39. (canceled)41. A pharmaceutical composition comprising a compound having the structure of a compound listed Table A claim 2 , or a pharmaceutically acceptable isomer claim 2 , racemate claim 2 , hydrate claim 2 , solvate claim 2 , isotope claim 2 , or salt thereof claim 2 , and a pharmaceutically acceptable excipient.4244-. (canceled)49. A compound having one of the structures listed in Table A claim 2 , or a pharmaceutically acceptable isomer claim 2 , racemate claim 2 , hydrate claim 2 , solvate claim 2 , isotope claim 2 , or salt thereof. The invention relates to modulators of the Mas-related G-protein coupled receptor X4, to products containing the same, as well as to methods of their use and preparation.Mas-related G protein receptors (MRGPRs) are a group of orphan receptors with limited expression in very specialized tissues. Very little is known about the function of most of these receptors. There are eight related receptors in this class expressed in humans, only four of which have readily identifiable orthologs in other species (i.e., MRGPR D, E, F and G). The other four receptors (MRGPR X1, X2, X3 and X4) have no counterpart, based on homology, in species ...

SELECTIVE SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS AND METHODS OF CHIRAL SYNTHESIS

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated. 147.-. (canceled)48. A method for the synthesis of a compound comprising an indane moiety having a chiral carbon in the five-membered ring of the indane moiety where the compound is enantiomerically enriched with respect to the chiral carbon , the method comprising the steps of(i) providing a compound comprising an indane moiety where the ring carbon of the five-membered ring of the indane moiety where chiral substitution is desired is oxo substituted at such carbon;{'sub': 2', '2-6', '3-8, '(ii) reacting such compound with a chiral reagent selected from the group consisting of a Corey Bakshita Shibata-oxazaborolidine and a chiral sulfinamide of the form RS(═O)NHwhere R is selected from the group consisting of t-butyl, branched Calkyl and Ccycloalkyl; and'}(iii) forming a chiral center at the indane moiety carbon previously bound to the oxo group by either reacting such compound with a suitable reducing agent along with the chiral reagent in step (ii) or reacting the result of the reaction of such compound with a suitable reducing agent.49. The method of wherein the chiral reagent is the Corey Bakshita Shibata-oxazaborolidine and the compound comprising an indane moiety is enantiomerically enriched with respect to a carbon-oxygen bond on a ring carbon of the five-membered ring of the indane moiety.50. The method of wherein the chiral reagent is (R)-(−)-(2)-methyl-CBS-oxazaborolidine or (S)-(−)-(2)-methyl-CBS-oxazaborolidine.51. The method of wherein the ...

SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS AND METHODS OF CHIRAL SYNTHESIS

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated. 2. The compound of wherein the compound has the structure of Formula I-R or a pharmaceutically acceptable salt claim 1 , ester claim 1 , prodrug claim 1 , homolog claim 1 , hydrate or solvate thereof.3. The compound of wherein the compound has the structure of Formula I-S or a pharmaceutically acceptable salt claim 1 , ester claim 1 , prodrug claim 1 , homolog claim 1 , hydrate or solvate thereof.4. The compound of wherein the compound is substantially enantiomerically pure.59-. (canceled)10. The compound of wherein Y is Cl.11. The compound of wherein Y is CF.12. The compound of wherein Y is CN.13. The compound of wherein X is —NR′R″.14. The compound of wherein X is —OR′″.15. The compound of wherein X is —OH.16. The compound of wherein X is —OCO—R.17. The compound of wherein Ris Calkyl.18. The compound of wherein R′ is H.19. The compound of wherein R′ is —COR.20. The compound of wherein R′ is —SO—R.21. The compound of wherein R″ is H.22. The compound of wherein R″ is —SO—R.23. The compound of wherein R″ is Calkyl optionally substituted with 1 or more R.24. The compound of wherein R″ is —(CRR)—R; each Rand each Ris independently selected from the group consisting of H claim 13 , hydroxyl and methyl or Rand Rbound to the same carbon taken together are oxo; and n is 0 claim 13 , 1 claim 13 , 2 claim 13 , or 3.25. The compound of wherein n is 2.26. The compound of wherein Ris —OH claim 25 , —NH claim 25 , —NHR claim 25 , —N(RR) claim 25 , or —COOH.27. The ...

SELECTIVE HETEROCYCLIC SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated. 4. The compound of wherein Ais S.5. The compound of wherein Ais S.6. The compound of wherein Ais S.7. The compound of wherein Ais N and Ais CH or N.8. The compound of wherein Ais CH.9. The compound of wherein Ais N.11. The compound of wherein Ris isopropyl or ethyl.12. The compound of wherein Y is —CN or —O—CH.2460.-. (canceled)65. A pharmaceutical composition comprising a compound of and a suitable excipient.6668.-. (canceled)69. A method of activation or agonism of a sphingosine-1-phosphate receptor subtype 1 comprising contacting the receptor subtype 1 with an effective amount of the compound of .7071.-. (canceled)72. A method of treatment of a malcondition in a patient for which activation or agonism of an sphingosine-1-phosphate receptor subtype 1 is medically indicated claim 1 , comprising administering an effective amount of the compound of to the patient at a frequency and for a duration of time sufficient to provide a beneficial effect to the patient.73. (canceled)74. The method of wherein the malcondition comprises multiple sclerosis claim 72 , transplant rejection claim 72 , acute respiratory distress syndrome claim 72 , ulcerative colitis claim 72 , influenza claim 72 , Crohn's disease or adult respiratory distress syndrome.75121.-. (canceled)123124.-. (canceled) This application claims priority to application Ser. No. 61/485,872, filed May 13, 2011, which is incorporated herein by reference in its entirety.The invention relates to compounds which ...

Novel glp-1 receptor stabilizers and modulators

Compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, methods of their therapeutic and/or prophylactic use, and methods of their use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor are provided. Certain compounds may have activity as modulators or potentiators with respect to glucagon receptor, GIP receptor, GLP-1 and GLP-2 receptors, and PTH receptor on their own or in the presence of receptor ligands such as GIP(1-42), PTH(1-34), Glucagon(1-29), GLP-2(1-33), GLP-1(7-36), GLP-1(9-36), oxyntomodulin and exendin variants.

NOVEL GLP-1 RECEPTOR MODULATORS

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “” represents either or both the R and S form of the compound): 3. (canceled)515-. (canceled)1729-. (canceled)30. The compound of wherein m is 2 claim 16 , a single Ris hydrogen claim 16 , each occurrence of Ris hydrogen claim 16 , and Ris hydrogen and R claim 16 , Rand Rare hydrogen.3146-. (canceled)47. The compound of wherein m is 1 claim 16 , Ris hydrogen and Rand Rtaken together with the atoms to which they are attached form a heterocyclyl optionally substituted with R.4849-. (canceled)50. The compound of wherein m is 2 claim 16 , Rof the second (CRR) group is hydrogen and Rand Rof the second (CRR) group taken together with the atoms to which they are attached form a heterocyclyl optionally substituted with R.5160-. (canceled)61. The compound of wherein Ris —N(R)—SO—R.6265-. (canceled)66. The compound of wherein Ris hydrogen.6768-. (canceled)69. The compound of wherein Ris —N(R)(R).7079-. (canceled)80. The compound of wherein Ris —N(R)(CRR)CON(R)(R).8182-. (canceled)83. The compound of wherein m is 1 claim 80 , Ris hydrogen and Rand Rtaken together with the atoms to which they are attached form a heterocyclyl optionally substituted with R.8485-. (canceled)86. The compound of wherein m is 2 claim 80 , Rof the second (CRR) group is hydrogen and Rand Rof the second (CRR) group taken together with the atoms to which they are attached form a heterocyclyl optionally substituted with R.8794-. (canceled)95. The compound of wherein Ris —N(R)(CRR)N(R)C(O)OR.9697-. (canceled)98. The compound of wherein Ris —N(R)(CRR)N(R)(R).99100-. ( ...

SELECTIVE SPHINGOSINE 1 PHOSPHATE RECEPTOR MODULATORS AND METHODS OF CHIRAL SYNTHESIS

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated. 171-. (canceled)73. The method of wherein the compound has the structure of Formula I-R or a pharmaceutically acceptable salt thereof.74. The method of wherein the pharmaceutically acceptable salt is a hydrochloric acid (HCl) salt.75. The method of wherein the compound has the structure of Formula I-S or a pharmaceutically acceptable salt thereof.76. The method of wherein the pharmaceutically acceptable salt is a hydrochloric acid (HCl) salt.78. The method of wherein the compound has the structure of Formula I-R or a pharmaceutically acceptable salt thereof.79. The method of wherein the pharmaceutically acceptable salt is a hydrochloric acid (HCl) salt.80. The method of wherein the compound has the structure of Formula I-S or a pharmaceutically acceptable salt thereof.81. The method of wherein the pharmaceutically acceptable salt a hydrochloric acid (HCl) salt. This application is a continuation application of U.S. application Ser. No. 15/170,686 filed Jun. 1, 2016, which is a continuation application of U.S. application Ser. No. 14/632,675 filed Feb. 26, 2015 (granted—U.S. Pat. No. 9,388,147 issued Jul. 12, 2016), which is a divisional of U.S. application Ser. No. 13/740,661 filed Jan. 14, 2013, which is a divisional of U.S. application Ser. No. 12/946,819 filed Nov. 15, 2010 (granted—U.S. Pat. No. 8,362,048 issued Jan. 29, 2013), which claims priority to U.S. Provisional Application No. 61/261,301, filed Nov. 13, 2009 and U.S. Provisional Application No. ...

Alquinil pirrolopirimidinas y analogos relacionados como inhibidores de hsp90.

Se describen alquinil pirrolo[2,3-d]pirimidinas y analogos relacionados y se demuestra que tienen utilidad como agentes inhibidores de proteina 90 de choque termico (HSP90) usados en el tratamiento y prevencion de varias alteraciones moderadas pro HSP90. Tambien se describen y reivindican metodos de sintesis y uso de tales compuestos.

Compounds having selective activity for retinoid X receptors, and means for modulation of processes mediated by retinoid X receptors

Compounds, compositions, and methods for modulating processes mediated by Retinoid X Receptors using retinoid-like compounds which have activity selective for members of the subclass of Retinoid X Receptors (RXRs), in preference to members of the subclass of Retinoic Acid Receptors (RARs). Examples of such compounds are bicyclic benzyl, pyridinyl, thiophene, furanyl, pyrrole, and polyenoic acid derivatives including carbocyclic polyenoic acids. The disclosed methods employ compounds for modulating processes selectively mediated by Retinoid X Receptors.

Orally Active Purine-Based Inhibitors of Heat Shock Protein 90

Novel purine compounds and tautomers and pharmaceutically acceptable salts thereof are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same. Methods of using the novel purine compounds of the invention, and tautomers and pharmaceutically acceptable salts thereof, include their use in inhibiting heat shock protein 90's (HSP90's) to thereby treat or prevent HSP90-dependent diseases, e.g., proliferative disorders such as breast cancer.

Novel glp-1 receptor stabilizers and modulators

Compounds that bind the glucagon-like peptide 1 receptor (GLP-1) receptor are provided including compounds which are modulators of the GLP-1 receptors and compounds which are capable of inducing a stabilizing effect on the receptor for use in structural analyses of the GLP-1 receptor. Methods of synthesis, methods of therapeutic and/or prophylactic use, and methods of use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor of such compounds are provided.

Carboxylic acid derivatives comprising four cycles that act as GLP-1 receptor modulators for the therapy of diseases such as diabetes

Un compuesto que tiene la estructura de Fórmula I-R o I-S o un isómero, enantiómero, racemato, sal, hidrato o solvato farmacéuticamente aceptable del mismo: **(Ver fórmula)** en donde A es un heterociclilo de 5, 6 o 7 miembros que tiene uno, dos o tres heteroátomos donde cada heteroátomo se selecciona independientemente entre O, N y S, y donde cualquier átomo del anillo de dicho heterociclilo puede estar opcionalmente sustituido con uno o más de R4; B es heterociclilo; C es arilo, arilalquilo, heterociclilo o heterociclilalquilo; Y1 e Y2 son ambos nulos; Z es -C(O)-; 55 cada R1 es independientemente H o C1-4 alquilo; R2 es, -OR8, -N(R1)-SO2-R8, -NR41R42, -N(R1)-(CRaRb)m-COOH, -N(R1)-(CRaRb)m-CO-N(Ri)-heterociclilo, - N(R1)-(CRaRb)m-CO-N(R1)(R7), o -N(R1)-heterociclilo, en donde R2 no -OH o -NH es 2; R3 es H, halo, alquilo, alquilo sustituido con R31, alcoxi, haloalquilo, perhaloalquilo, haloalcoxi, perhaloalcoxi, arilo, heterociclilo, -OH, -OR8, -CN, -NO2, -NR1R8, -C(O)R8, -C(O)NR1R8, -NR1C(O)R8, -SR8, -S(O)R8, - S(O)2R8, -OS(O)2R8, -S(O)2NR1R8, -NR1S(O)2R8, -(CRaRb)mNR1R8, -(CRaRb)mO(CRaRb)mR8, - (CRaRb)mNR1(CRaRb)mR8 o -(CRaRb)mNR1(CRaRb)mCOOH; R4 es H, alquilo, alquilo sustituido con R31, alcoxi, haloalquilo, perhaloalquilo, haloalcoxi, perhaloalcoxi, arilo, heterociclilo, -OH, -OR8, -CN, -NO2, -NR1R8, -C(O)R8, -C(O)NR1R8, -NR1C(O)R8, -SR8, -S(O)R8, -S(O)2R8, - OS(O)2R8, -S(O)2NR1R8, -NR1S(O)2R8, -(CRaRb)mNR1R8, -(CRaRb)mO(CRaRb)mR8, -(CRaRb)mNR1(CRaRb)mR8 o -(CRaRb)mNR1(CRaRb)mCOOH; o cualesquiera dos grupos R3 o R4 en el mismo átomo de carbono tomados juntos forman oxo; cada R31 es independientemente H, halo, hidroxilo, -NR41R42 o alcoxi; cada R40 es independientemente H o alquilo; cada R41 y R42 es independientemente R40 o-(CH2)n-COO-R40, -C(O)-R40, arilo, heteroarilo, o dos tomados junto con el átomo de N al que están unidos pueden formar un heterociclilo de 3 a 7 miembros; W1 es nulo o -L1-(CRaRb)m-L1-R6; cada L1 es independientemente, desde el extremo ...

Glp-1 receptor modulators

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where "^^^^" represents either or both the R and S form of the compound) (I) where A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined herein.

Compounds having selectivity for retinoid x receptors

Compounds, compositions, and methods for modulating processes mediated by Retinoid X Receptors using retinoid-like compounds which have activity selective for members of the subclass of Retinoid X Receptors (RXRs), in preference to members of the subclass of Retinoic Acid Receptors (RARs). Examples of such compounds are bicyclic benzyl, pyridinyl, thiophene, furanyl, and pyrrole derivatives. The disclosed methods employ compounds for modulating processes selectively mediated by Retinoid X Receptors.

Triazolopyrimidines and related analogs as HSP90-inhibitors

Triazolopyrimidines and related compounds are described and demonstrated or predicted to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents in the treatment and prevention of various HSP90 mediated disorders, e.g., proliferative disorders. Method of synthesis and use of such compounds are also described and claimed.

Novel glp-1 receptor modulators

The invention relates to compounds that are characterized by possessing at least four cycles (A-C and phenylene ring). Such compounds modulate the glucagon-like peptide 1 (GLP-1) receptor and have a therapeutic use that includes diseases such as diabetes, obesity and excessive appetite. The compounds act as modulators or potentiators of the GLP-1 receptor, or act with receptor ligands including GLP-1 peptides GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide. Claimed are compounds of the fol lowing genera structure (" ? "1 represents undefined stereochemistry) : [Formula I] where the variables A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined in the claims.

Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the SlP receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds are provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

Dimer-selective RXR modulators and methods for their use

Dimer-selective RXR modulator compounds having agonist, partial agonist and/or antagonist activity in the context of an RXR homodimer and/or RXR heterodimers are provided. Also provided are pharmaceutical compositions incorporating such dimer-selective RXR modulator compounds and methods for their therapeutic use.

selective sphingosine 1 phosphate receptor modulators, their use, and composition

compostos moduladores seletivos de receptor de esfingosina 1 fosfato, seus uso e método de síntese, bem como combinação farmacêutica e kit. a presente invenção se refere a compostos que modulam seletivamente o receptor de esfingosina 1 fosfato, incluindo compostos que modulam o subtipo 1 do receptor s1p. proporcionam-se os métodos de síntese quiral desses compostos. os usos, os métodos de tratamento ou prevenção, e os métodos de preparação das composições inventivas, incluindo os compostos inventivos, são proporcionados em relação ao tratamento ou prevenção de doenças, más condições, e distúrbios aos quais a modulação do receptor de esfingosina 1 fosfato é medicamente indicada. selective sphingosine 1 phosphate receptor modulator compounds, their use and method of synthesis, as well as pharmaceutical combination and kit. The present invention relates to compounds that selectively modulate the sphingosine 1 phosphate receptor, including compounds that modulate subtype 1 of the s1p receptor. methods of chiral synthesis of these compounds are provided. uses, methods of treatment or prevention, and methods of preparing the inventive compositions, including the inventive compounds, are provided in relation to the treatment or prevention of diseases, conditions, and disorders to which the modulation of the sphingosine 1 phosphate receptor it is medically indicated.

Novel glp-1 receptor modulators

The invention relates to compounds that are characterized by possessing at least four cycles (A-C and phenylene ring). Such compounds modulate the glucagon-like peptide 1 (GLP-1) receptor and have a therapeutic use that includes diseases such as diabetes, obesity and excessive appetite. The compounds act as modulators or potentiators of the GLP-1 receptor, or act with receptor ligands including GLP-1 peptides GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide. Claimed are compounds of the fol lowing genera structure (" ? "1 represents undefined stereochemistry) : [Formula I] where the variables A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined in the claims.

Means for the modulation of processes mediated by retinoid receptors and compounds useful therefor

A method for modulating lipid metabolism in a subject by administering 9-cis retinoic acid is presented. The 9-cis retinoic acid is more specific for the retinoid X receptor than is retinoic acid.

Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis

Selective sphingosine 1 phosphate receptor modulators and combination therapy therewith

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided, including compounds which modulate subtype 1 of the S1P receptor, and methods of their therapeutic and/or prophylactic use in combination with at least one other medicament adapted for treatement of a malcondition for which activation of S1P 1 is medically indicated, such as multiple sclerosis.

NEW GLP-1 RECEIVER MODULATORS

NOVOS MODULADORES DO RECEPTOR DE GLP-1 (I) O documento provê compostos que modulam o receptor do peptídeo 1 semelhante ao glucagon, bem como métodos de síntese e métodos para emprego terapêutico e/ou profilático dos mesmos. Tais compostos podem atuar como moduladores ou potenciadores do receptor de GLP-1 propriamente ou com peptídeos de incretina, tais como, GLP-1 (7-36) e GLP-1 (9-36) ou com terapias à base de peptídeo, tais como, exanatide e liraglutide e possui a estrutura da fórmula geral acima (onde "(I)" representa tanto uma ou ambas as formas R e S do composto): em que A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p e q são conforme definidos no presente documento. NEW GLP-1 RECEPTOR MODULATORS (I) The document provides compounds that modulate the glucagon-like peptide 1 receptor, as well as methods of synthesis and methods for their therapeutic and/or prophylactic use. Such compounds may act as GLP-1 receptor modulators or enhancers by themselves or with incretin peptides such as GLP-1 (7-36) and GLP-1 (9-36) or with peptide-based therapies such as as, exanatide and liraglutide and has the structure of the general formula above (where "(I)" represents either one or both of the R and S forms of the compound): wherein A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined herein.

Drug formulations having long and medium chain triglycerides

Drug formulations having emulsifying agents and both medium and long chain triglycerides are described. In preferred embodiments, the long chain triglycerides negate or lessen deleterious central nervous system effects that are caused by medium chain triglycerides.

Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis.

Se proporcionan compuestos que modulan de manera selectiva el receptor de esfingosina 1 fosfato incluyendo compuestos que modulan el subtipo 1 deI receptor de S1P. Se proporcionan métodos de síntesis quiral de tales compuestos. Se proporcionan usos, métodos de tratamiento o prevención y métodos para preparar composiciones inventivas incluyendo compuestos inventivos en relación con el tratamiento o prevención de enfermedades, condiciones anormales, y trastornos para los cuales la modulación del receptor de esfingosina 1 fosfato se indica médicamente.

Modulators of mas-related g-protein receptor x4 and related products and methods

Methods are provided for modulating MRGPR X4 generally, or for treating a MRGPR X4 dependent condition more specifically, by contacting the MRGPR X4 or administering to a subject in need thereof, respectively, an effective amount of a compound having the structure of Formula (I): or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein m, n, p, t, A, B, Z, R1, R2 and R3 are as defined herein. Pharmaceutical compositions containing such compounds, as well as to compounds themselves, are also provided. The Mas-Related G-protein (MRGPR) X4 modulators, are in particular isoindolinones and isoquinolinones substituted on the carbocyclic ring. The compounds are useful to treat itch associated conditions, pain associated conditions, or an autoimmune disorder.

Compounds having selectivity for retinoid x receptors

Compounds, compositions, and method for modulating processes mediated by Retinoid X Receptors using retinoid-like compounds which have activity selective for members of the subclass of Retinoid X Receptors (RXRs), in preference to members of the subclass of Retinoic Acid Receptors (RARs). Examples of such compounds are bicyclic benzyl, pyridinyl, thiophene, furanyl, and pyrrole derivatives. The disclosed methods employ compounds for modulating processes selectively mediated by Retinoid X Receptors.

Novel trienoic retinoid compounds and methods

Novel trienoic retinoid compounds having activity for retinoic acid receptors and retinoid X receptors are provided. Also provided are pharmaceutical compositions incorporating such compounds and methods for their use. Compounds of the following formulae are provided: <IMG>

Pyrrolopyrimidines and related analogs as HSP90-inhibitors

The present invention provides compounds represented by Formula I. R 0 is selected from hydrogen, halogen, lower alkyl, —SR 8 , —OR 8 , —CN, and —NHR 8 , R 1 is halogen, or lower alkyl; R 2 is —NHR 8 ; R 3 is selected from the group consisting of hydrogen, halogen, —SR 8 , —OR 8 , —CN, —C(O)R 9 , —C(O)OH, —NO 2 , —NR 8 R 10 , lower alkyl, lower alkenyl, lower alkynyl, lower perhaloalkyl, aryl, heteroaryl, alicyclic and heterocyclic, all optionally substituted, and R 5 is aryl, heteroaryl, alicyclic, or heterocyclic:

Selective heterocyclic sphingosine 1 phosphate receptor modulators.

Se proporcionan compuestos que modulan de manera selectiva el receptor de esfingosina 1 fosfato incluyendo compuestos que modulan el subtipo 1 del receptor de S1P. Se proporcionan métodos de síntesis quiral de tales compuestos. Se proporcionan usos, métodos de tratamiento o prevención y métodos para preparar composiciones inventivas incluyendo compuestos inventivos en relación con el tratamiento o prevención de enfermedades, condiciones anormales, y trastornos para los cuales la modulación del receptor de esfingosina 1 fosfato se indica médicamente.

Means for the modulation of processes mediated by retinoid receptors and compounds useful therefor

In accordance with the present invention, there are provided methods to modulate processes mediated by retinoid recep-tors, employing high affinity, high specificity ligands for such receptors. In one aspect of the present invention, there are provided ligands which are more selective for the retinoid X receptor than is retinoic acid (i.e., rexoids). In another aspect of the present invention, alternative ligands (other than retinoic acid) have been discovered which are capable of inducing retinoic acid receptor mediated processes. In yet another aspect, methods have been developed for the preparation of such retinoid receptor ligands from readily available compounds.

Drug formulations having long and medium chain triglycerides

Dimer-selective rxr modulators and methods for their use

Dimer-selective RXR modulator compounds having agonist, partial agonist and/or antagonist activity in the context of an RXR homodimer and/or RXR heterodimers are provided. Also provided are pharmaceutical compositions incorporating such dimer-selective RXR modulator compounds and methods for their therapeutic use.

Carboxylic acid derivatives comprising four cycles acting as glp-1 receptor modulators for therapy of diseases such as diabetes

Disclosed herein are compounds represented by formulae I-R and I-S possessing four cycles (A, B, C and phenylene ring) where the substituents are as defined herein. Such compounds modulate the glucagon-like peptide 1 (GLP-1) receptor and have a therapeutic use that includes diseases such as diabetes, obesity and excessive appetite. The compounds act as modulators or potentiators of the GLP-1 receptor, or act with receptor ligands including GLP-1 peptides GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide.

Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the SlP receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

Cytotoxins and diagnostic imaging agents comprising hsp90 ligands

Cytotoxic compounds and diagnostic imaging agents comprising HSP90-ligands and methods of use thereof are described.

New stabilizers and modulators of the GLP-1 receptor

Un compuesto que tiene la estructura de Fórmula II**Fórmula** o un estereoisómero, tautómero, isótopo, enantiómero, sal, hidrato o solvato farmacéuticamente aceptable del mismo, en donde R1 es R13 u -O-(CH2)n-R13 o R10; cada R10, R11 y R12 es independientemente H o alquilo; R13 es cicloalquilo, heterocicloalquilo, arilo o heteroarilo, o un biciclo condensado de dos cualquiera de tales restos de anillo, donde cualquier átomo de anillo de R13 puede estar opcionalmente sustituido con uno o más R14 o R15; cada R14 es independientemente H, alquilo, halo, hidroxi, ciano, alcoxi, perhaloalquilo y perhaloalcoxi, -OR10, - (CH2)n-COOR10, -SR10, -SO-R10, -SO2R10, -NR11R12, -NHCO(CH2)n-R12, -N(R11)CO(CH2)n-R12 o -NH(CH2)n-R12; R15 es cicloalquilo, heterocicloalquilo, arilo o heteroarilo, o un biciclo condensado de dos cualquiera de tales restos de anillo, donde cualquier átomo de anillo de R15 puede estar opcionalmente sustituido con uno o más R14; cada R20 es independientemente H o alquilo; L2 es oxazolilo, oxadiazolilo, triazolilo, pirazolilo o pirimidinilo; R2 es R26, -O-(CH2)n-R26, R23 u -O-(CH2)n-R23; R23 es cicloalquilo, heterocicloalquilo, arilo o heteroarilo, o un biciclo condensado de dos cualquiera de tales restos de anillo, donde cualquier átomo de anillo de R23 puede estar opcionalmente sustituido con uno o más de R24 y en donde un átomo de anillo de R23 está opcionalmente sustituido con L3-R25; cada R24 se selecciona independientemente entre H, halo, alquilo, hidroxi, oxo, ciano, alcoxi, perhaloalquilo, perhaloalcoxi, nitro o amino, -O-(CH2)n-R21, -(CH2)n-O-R21, -O-(CH2)n-O-R21, -(CH2)n-NR21R22, -(CH2)n- N(R21)CO(CH2)n-R21, -(CH2)n-N(R21)SO2(CH2)n-R21, -(CH2)n-SO2-N(R21)-(CH2)n-R21, -(CH2)n-CO(CH2)n-R21, - (CH2)m-COO-R21, -O-(CH2)n-COO-R21 o -(CH2)n-OCO-R21; cada R21 y R22 es independientemente H o alquilo, -(CH2)n-COOH, o dos tomados junto con el átomo de nitrógeno al que están unidos pueden formar un anillo heterocíclico de 3 a 7 miembros; L3 es nulo, -O-, -(CH2) ...

GLP-1 receptor modulators

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36), GLP-1(9-36), and oxyntomodulin, or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where “ ” represents either or both the R and S form of the compound): where A, B, C, R 1 , R 2 , R 3 , R 4 , R 5 , n, p and q are as defined herein.

Isotopically-labeled retinoids, their production and use

Modulators of mas-related g-protein receptor x2 and related products and their use

Methods are provided for modulating MRGPRX2 or a MRGPRX2 ortholog generally, or for treating a MRGPRX2 or a MRGPRX2 ortholog dependent condition more specifically, by contacting the MRGPRX2 or the MRGPRX2 ortholog by administering to a subject in need thereof, respectively, an effective amount of a compound having structure (I): or a pharmaceutically acceptable salt, isomer, hydrate, solvate or isotope thereof, wherein W, Z, R1, R2, R3, R4, R5, R6 and Rx are as defined herein. Pharmaceutical compositions containing such compounds, as well as the compounds themselves, are also provided.

Ansamycins having improved pharmacological and biological properties

Ansamycins and methods of preparing and using the same are described. At least some of these ansamycins exhibit one or more of improved aqueous formulation ability, chemical stability, and bioavailability. Some of the derivatives described are dimers. These and others described can include one or more solubilizing groups that have expected merit in rendering the overall compounds useful as drugs and prodrugs.

Novel heterocyclic compounds as hsp90-inhibitors

Novel heterocyclic compounds are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agent. Method of synthesis and use of such compounds are also described.

Selective heterocyclic sphingosine 1 phosphate receptor modulators

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the SlP receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

Retinoic acid derivatives

Compounds with retinoid x receptor selectivity

Alkynyl pyrrolopyrimidines and related analogs as hsp90-inhibitors

Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders. Methods of synthesis and use of such compounds are also described and claimed.

ALKYNYL PYRROLO[2,3-d]PYRIMIDINES AND RELATED ANALOGS AS HSP90-INHIBITORS

Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders. Methods of synthesis and use of such compounds are also described and claimed.

Selective sphingosine 1 phosphate receptor modulators and methods of chiral synthesis

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the S1P receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

Novel trienoic retinoid compounds and methods

Novel trienoic retinoid compounds having activity for retinoic acid receptors and retinoid X receptors are provided. Also provided are pharmaceutical compositions incorporating such compounds and methods for their use.

Selective heterocyclic sphingosine 1 phosphate receptor modulators

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the SlP receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

Dimer-selective RXR modulators and methods for their use

Dimer-selective RXR modulator compounds having agonist, partial agonist and/or antagonist activity in the context of an RXR homodimer and/or RXR heterodimers are provided. Also provided are pharmaceutical compositions incorporating such dimer-selective RXR modulator compounds and methods for their therapeutic use. <IMAGE> <IMAGE> <IMAGE>

7,9-dihydro-purin-8-one and related analogs as hsp90-inhibitors

The invention relates in general to 7,9-dihydro-purin-8-one and related compounds that show broad utility, e.g., in inhibiting heat shock protein 90 (HSP90) to thereby treat or prevent HSP90-mediated diseases.

(pyridinyl and pyrimidyl) trienoic acid derivatives as retinoid x receptor modulators

The present invention relates to a method of modulating retinoid X receptor activity in a mammal, novel compounds and pharmaceutical compositions for modulating retinoid X receptor activity in a mammal, and methods of making compounds that modulate retinoid X receptor activity in a mammal. The compounds are represented by Structural Formula I: The compounds of Structur al Formula I are efficacious insulin sensitizers and do not have the undesirabl e side effects of increasing triglycerides or suppressing the thyroid hormone axis.

New GLP-1 receptor modulators

Un método para adquirir una imagen coloreada escaneando una superficie coloreada (2) de un azulejo (3), que comprende las etapas de: proporcionar una matriz de fotodetectores (4) que comprende una pluralidad de filas de fotodetectores (5) que son paralelos y colocados uno al lado del otro, la matriz de fotodetectores (4) no comprende ningún filtro de color por encima de los fotodetectores (4) y las filas de fotodetectores (5) están cercanas entre sí y espaciadas por una distancia igual a al menos un píxel, en donde cada fila de fotodetectores (4) es capaz de detectar la imagen de una tira elemental de una banda de superficie (6) de una superficie coloreada (2) de un azulejo para escanearla; posicionar la matriz de fotodetectores (4) tal como para adquirir una imagen de la banda de superficie (6) de la superficie coloreada (2) de un azulejo (3), estando cada fila de fotodetectores tal como para adquirir la imagen de una tira elemental correspondiente de la banda de superficie ordenar a la matriz de fotodetectores (4) tal como para que adquiera la imagen de la banda de superficie (6) en sincronía con un intervalo de escaneo temporal, en donde, para cada intervalo de escaneo temporal, cada fila de fotodetectores adquiere la imagen de una tira elemental correspondiente de la banda de superficie; proporcionar una pluralidad de lámparas (7), cada una de las cuales tiene un espectro de emisión de luz diferente del espectro de emisión de luz de una lámpara adicional de la pluralidad de lámparas (7); colocar la pluralidad de lámparas (7) de tal manera que iluminen la banda de superficie (6) de la superficie coloreada (2) del azulejo (3) a escanear; ordenar a las lámparas de la pluralidad de lámparas (7) en una secuencia de ciclo de encendido en donde se ordena que se encienda solo una de las lámparas cada vez para cada intervalo de escaneo temporal; proporcionar un medio de transporte (8) para recibir y transportar en reposo el azulejo (3) a escanear y para determinar un ...

Process for preparing 17-allyl amino geldanamycin (17-aag) and other ansamycins

Efficient chemical processes for preparing high yields, purities, and different polymorphic forms of 17-allyl amino geldanamycin (17-AAG) and other ansamycins are described and claimed.

Phospholipid-based pharmaceutical formulations and methods for producing and using same

Pharmaceutical formulations and methods of producing and using the same are described and claimed. The formulations are dispersions of phospholipids and one or more pharmacologically active compounds, pharmaceutically acceptable salts thereof, or prodrugs thereof. In specific embodiments, the pharmaceutically active compounds are ansamycins and the overall formulation is substantially devoid of medium and long chain triglycerides.

Compounds having selective activity for retinoid x receptors, and means for modulation of processes mediated by retinoid x receptors

Compounds, compositions, and methods for modulating processes mediated by Retinoid X Receptors using retinoid-like compounds which have activity selective for members of the subclass of Retinoid X Receptors (RXRs), in preference to members of the subclass of Retinoic Acid Receptors (RARs). Examples of such compounds are bicyclic benzyl, pyridinyl, thiophene, furanyl, pyrrole, and polyenoic acid derivatives including carbocyclic polyenoic acids. The disclosed methods employ compounds for modulating processes selectively mediated by Retinoid X Receptors.

Alkynyl pyrrolopyrimidines and related analogs as hsp90-inhibitors

Alkynyl pyrrolo[2,3-d]pyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders. Methods of synthesis and use of such compounds are also described and claimed.

Novel glp-1 receptor modulators glp-1

Novel glp-1 receptor stabilizers and modulators

Compounds that bind the glucagon-like peptide 1 (GLP-1) receptor, methods of their synthesis, methods of their therapeutic and/or prophylactic use, and methods of their use in stabilizing GLP-1 receptor in vitro for crystallization of the GLP-1 receptor are provided. Certain compounds may have activity as modulators or potentiators with respect to glucagon receptor, GIP receptor, GLP-1 and GLP-2 receptors, and PTH receptor on their own or in the presence of receptor ligands such as GIP(1-42), PTH(1-34), Glucagon(1-29), GLP-2(1-33), GLP-1 (7-36), GLP-1 (9-36), oxyntomodulin and exendin variants.

1-h-pyrazolo[3,4b]pyrimidine derivatives and their use as modulators of mitotic kinases

The invention relates to compounds of Formula (I), a polymorph, an enantiomer, a stereoisomer, a solvate, an N-oxide derivative, or a pharmaceutically acceptable salt thereof: Formula (I), which have inhibitory effect on one or more protein kinases that are involved in cell mitosis.

Novel glp-1 receptor modulators

Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where "(Ⅰ)" represents either or both the R and S form of the compound): where A, B, C, Y 1 , Y 2 , Z, R 1 , R 2 , R 3 , R 4 , R 5 , W 1 , n, p and q are as defined herein.

Compounds having selective activity for retinoid X receptors, and means for modulation of processes mediated by retinoid X receptors

Compounds, compositions, and methods for modulating processes mediated by Retinoid X Receptors using retinoid-like compounds which have activity selective for members of the subclass of Retinoid X Receptors (RXRs), in preference to members of the subclass of Retinoic Acid Receptors (RARs). Examples of such compounds are bicyclic benzyl, pyridinyl, thiophene, furanyl, and pyrrole derivatives. The disclosed methods employ compounds for modulating processes selectively mediated by Retinoid X Receptors.

PROCESS FOR THE PREPARATION OF 17-ALLYL-AMINO-GELDANAMYCIN (17-AAG) AND OTHER ANSAMYCINE

Novel glp-1 receptor modulators

Compounds having selectivity for retinoid x receptors

Compounds, compositions, and methods for modulating processes mediated by Retinoid X Receptors using retinoid-like compounds which have activity selective for members of the subclass of Retinoid X Receptors (RXRs), in preference to members of the subclass of Retinoic Acid Receptors (RARs). Examples of such compounds are bicyclic benzyl, pyridinyl, thiophene, furanyl, and pyrrole derivatives. The disclosed methods employ compounds for modulating processes selectively mediated by Retinoid X Receptors.

Triazolopyrimidines and related analogs as HSP90-inhibitors

A compound represented by Formula I, or a polymorph, ester, tautomer, enantiomer, diastereomer, pharmaceutically acceptable salt or prodrug thereof, Wherein R 1 is halogen, —OR 11 , —SR 11 or lower alkyl; R 2 is —NHR 8 ; R 4 is —CHR 12 —, —C(O)—, —C(S)—, —S(O)— or —S 2 —; and R 5 is aryl, heteroaryl, alicyclic, or heterocyclic, wherein the aryl group is substituted with 4 to 5 substituents, the heteroaryl group is substituted with 3 to 5 substituents, the alicyclic group is substituted with 3 to 5 substituents, and the heterocyclic group is substituted with 3 to 5 substituents.

Purine analogs having HSP90-inhibiting activity

Novel purine compounds of Formula I. and tautomers, pharmaceutically acceptable salts, and prodrugs thereof, wherein X is S, S(O), or S(O) 2 ; and O is selected from alkyl, cycloalkyl, arylalkyl, aryl, heteroaryl, and heterocyclic, all optionally substituted, are described, as are pharmaceutical compositions comprising the same, complexes comprising the same, e.g., HSP90 complexes, and methods of using the same.

Novel trienoic retinoid compounds and methods

Novel trienoic retinoid compounds having activity for retinoic acid receptors and retinoid X receptors are provided. Also provided are pharmaceutical compositions incorporating such compounds and methods for their use.

Carboxylic acid derivatives comprising four cycles acting as glp-1 receptor modulators for therapy of diseases such as diabetes glp-1

Sphingosine 1 phosphate receptor modulators and methods of chiral synthesis

Compounds that selectively modulate the sphingosine 1 phosphate receptor are provided including compounds which modulate subtype 1 of the SlP receptor. Methods of chiral synthesis of such compounds is provided. Uses, methods of treatment or prevention and methods of preparing inventive compositions including inventive compounds are provided in connection with the treatment or prevention of diseases, malconditions, and disorders for which modulation of the sphingosine 1 phosphate receptor is medically indicated.

New trienoic retinoid compounds and methods

Modulators of mitotic kinases

The invention relates to compounds of Formula (I), a polymorph, an enantiomer a stereoisomer, a solvate, an N-oxide, or a pharmaceutically acceptable salt thereof; which have inhibitory effect on one or more protein kinases that are involved in cell mitosis.

VITAMIN D3 MIMETISTS

Retinoid x receptor modulators

The present invention is directed to compounds represented by Structural Formula (I) and pharmaceutically acceptable salts, solvates and hydrates thereof: (I). The invention is also directed to pharmaceutical compositions, methods of use and methods of making compounds represented by Structural Formula (I) and pharmaceutically acceptable salts, solvates and hydrates thereof.