Abstract: Compounds of formula (I) are modulators of cannabinoid receptor CB1, useful inter alia for treatment of obesity: Formula (I).

Abstract: Compounds of formula (I) suppress the normal signalling activity CB1 receptors, and are thus useful in the treatment of diseases or conditions which are mediated by CB1 receptor signalling activity, such as treatment of obesity and overweight, prevention of weigh gain, treatment of diseases and conditions directly or indirectly associated with obesity and overweight: wherein A1 is hydrogen, —COOH, or tetrazolyl; p and q are independently 0 or 1; A3 is phenyl or cycloalkyl, either of which is optionally substituted with R4 and/or R5; R4 and R5 are independently —R9, —CN, —F, —Cl, —Br, —OR9, —NR7R8, —NR7COR6, —NR7SO2R6, —COR6, —SR9, —SOR9, or —SO2R6; R6 is C1-C4 alkyl, cycloalkyl, —CF3 or —NR7R8; R7 and R8 are independently hydrogen, C1-C4 alkyl or cycloalkyl; R9 is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkoxy(C1-C4 alkyl)-, cycloalkyl, or fully or partially fluorinated C1-C4 alkyl; R1 (i) a bond; (ii) a divalent radical of formula —(CH2)aB1(CH2)b wherein a and b are independently O, 1, 2 or 3 provided tha

Abstract: Compounds of formula (I) suppress the normal signalling activity CB1 receptors, and are thus useful in the treatment of diseases or conditions which are mediated by CB1 receptor signalling activity, such as treatment of obesity and overweight, prevention of weigh gain, treatment of diseases and conditions directly or indirectly associated with obesity and overweight: wherein A1 is hydrogen, —COOH, or tetrazolyl, and A2 is hydrogen, —COOH, or tetrazolyl, provided that one of A1 and A2 is either —COOH or tetrazolyl; p is 0 or 1 and A3 is phenyl or cycloalkyl, either of which is optionally substituted with R4 and/or R5; q is 0 or 1; R3 is hydrogen, C1-C4 alkyl, cycloalkyl, —CF3, or —OR9; R4 and R5 independently —R9, —CN, —F, —Cl, —Br, —OR9, —NR7R8, —NR7COR6, —NR7SO2R6, —COR6, —SR9, —SOR9, or —SO2R6; R6 is C1-C4 alkyl, cycloalkyl, —CF3 or —NR7R8; R7 and R8 are independently hydrogen, C1-C4 alkyl, —CF3, or cycloalkyl; R9 is hydrogen, C1-C4 alkyl, cycloalkyl, fully or partially fluorinated C1-C4 alkyl; R1 is

Abstract: Compounds of formula (I) are useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis: wherein A represents a carboxyl group —COOH, or a carboxyl bioisostere; A1 is hydrogen or methyl; ring Ar1 is an optionally substituted phenyl ring or 5- or 6-membered monocyclic heteroaryl ring, in which AA1CHO— and L2 are linked to adjacent ring atoms; rings Ar2, Ar3 each independently represent a phenyl or 5- or 6-membered monocyclic heteroaryl ring, or a bicyclic ring system consisting of a 5- or 6-membered carbocyclic or heterocyclic ring which is benz-fused or fused to a 5- or 6-membered monocyclic heteroaryl ring, said ring or ring system being optionally substituted; t is 0 or 1; L2 and L3 are linker radicals as defined in the description.

Abstract: Y4 receptor agonist peptide selected from the group consisting of: [Ala30]PP2-36, [Thr30]PP2-36, [Asn30]PP2-36, [Gln30]PP2-36, [Glu10]PP2-36, [Glu10,Leu17,Thr30]PP2-36, [Nle17,Nle30]PP2-36, [Glu10,Nle17,Nle30]PP2-36, their PP1-36 equivalents, and analogues and derivatives thereof as described in the specification, are selective agonists of the Y4 receptor relative to the Y1 and Y2 receptors, and are useful in the treatment, for example, of obesity and overweight, and conditions in which these are considered contributory factors, and in the treatment of diarrhoea and intestinal hypersecretion.

Abstract: Compounds of formula (I) are useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis, wherein A represents a carboxyl group —COON, or a carboxyl bioisostere; A1, is hydrogen or methyl; ring Ar1 is an optionally substituted phenyl ring 5- or 6-membered monocyclic heteroaryl ring, in which AA1CHO— and L2 are linked to adjacent ring atoms; rings Are2, Ar3 each independently represent a phenyl or 5- or 6-membered monocyclic heteroaryl ring, or a bicyclic ring system consisting of a 5- or 6-membered carbocyclic or heterocyclic ring which is benz-fused or fused to a 5- or 6-membered monocyclic heteroaryl ring, said ring or ring system being optionally substituted; t is 0 or 1; L2 and L3 are linker radicals as defined in the description.

Abstract: The modified human PP peptides (i) [Lys4,Leu17,Ser30,Gln34]hPP, (ii) Lys4,Leu17,Thr30,Gln34]hPP; and (iii) [Lys4,Leu17,oxidised Met30,Gln34]hPP wherein “oxidised Met” may be the sulfoxide or sulfone, and certain analogues and derivatised forms thereof as referred to in the specification, are selective agonists of the Y2 receptor relative to the Y1 and Y4 receptors, and are useful for, for example, appetite control and therapeutic angiogenesis.

Abstract: Compounds of formula (I) are modulators of cannabinoid receptor CB1, useful inter alia for treatment of obesity: Formula (I). Wherein: X is a bond, or a divalent radical selected from —C(R10)(R11)—*, —C(R10)(R11)—O—*, —C(R10)(R11)CH2—*, —C(R10)(R11)CH2—O—*, —CH2C(R10)(R11)—*, —CH2C(R10)(R11)—O—*.

Abstract: Human Pancreatic Polypeptide mutants are provided which have utility, inter alia, for regulation of energy intake or energy metabolism, control of intestinal secretion, decrease of gastrointestinal tract motility, decrease of rate of gastric emptying, treatment of obesity or overweight, or conditions in which obesity or overweight is a contributory factor.

Abstract: Compounds of formula (I) suppress the normal signalling activity CB1 receptors, and are thus useful in the treatment of diseases or conditions which are mediated by CB1 receptor signalling activity, such as treatment of obesity and overweight, prevention of weigh gain, treatment of diseases and conditions directly or indirectly associated with obesity and overweight: wherein A1 is hydrogen, —COOH,or tetrazolyl; p and q are independently 0 or 1; A3 is phenyl or cycloalkyl, either of which is optionally substituted with R4 and/or R5; R4 and R5 are independently —R9, —CN, —F, —Cl, —Br, —OR9, —NR7R8, —NR7COR6, —NR7SO2R6, —COR6, —SR9, —SOR9, or —SO2R6; R6 is C1-C4 alkyl, cycloalkyl, —CF3 or —NR7R8; R7 and R8 are independently hydrogen, C1-C4 alkyl or cycloalkyl; R9 is hydrogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 alkoxy(C1-C4 alkyl)-, cycloalkyl, or fully or partially fluorinated C1-C4 alkyl; R1 (i) a bond; (ii) a divalent radical of formula —(CH2)aB1(CH2)b wherein a and b are independently O, 1, 2 or 3 provided that

Abstract: Y4 receptor agonist peptide selected from the group consisting of: [Ala30]PP2-36, [Thr30]PP2-36, Asn30]PP2-36, [Gln30]PP2-36, [Glu10]PP2-36, [Glu10,Leu17,Thr30]PP2-36, [Nle17,Nle30]PP2-36, [Glu10,Nle17,Nle30]PP2-36, their PP1-36 equivalents, and analogues and derivatives thereof as described in the specification, are selective agonists of the Y4 receptor relative to the Y1 and Y2 receptors, and are useful in the treatment, for example, of obesity and overweight, and conditions in which these are considered contributory factors, and in the treatment of diarrhoea and intestinal hypersecretion.

Abstract: Compounds of formula (I) are useful in the treatment of disease responsive to modulation of CRTH2 receptor activity, wherein: A represents a carboxyl group —COOH, or a carboxyl bioisostere; L1 is a bond, —CH2—, —OCH2—, —CH2CH2— or —CH?CH—; L2 is CONH—, —NHCO—, SO2NR1—, —NR1SO2 wherein R1 is hydrogen or C1-C3 alkyl, or a divalent radical of formula (X) or (Y), wherein ring Q is a non aromatic heterocyclic ring containing 5 to 7 ring atoms, including the nitrogen shown; L3 is a divalent linker radical of formula -(Alk1)m-(Z)n-(Alk2)p as defined in the description; ring Ar1 is an optionally substituted divalent phenyl radical or divalent 5- or 6-membered monocyclic heteroaryl radical, in which L1 and the H[B]sL3L2Ar2CONH-radical are linked to adjacent ring carbon atoms; ring Ar2 is an optionally substituted 1,3-phenylene radical, or an optionally substituted divalent 5- or 6-membered monocyclic heteroaryl radical, in which AL1Ar1NHCO-radical and the H[B]sL3L2-radical are linked to ring carbon atoms which are not

Abstract: Compounds of formula (I) are useful for the treatment of disease responsive to modulation of CRTH2 receptor activity, such as asthma, rhinitis, allergic airway syndrome, and allergic rhinobronchitis, wherein A represents a carboxyl group —COON, or a carboxyl bioisostere; A1, is hydrogen or methyl; ring Ar1 is an optionally substituted phenyl ring 5- or 6-membered monocyclic heteroaryl ring, in which AA1CHO— and L2 are linked to adjacent ring atoms; rings Are2, Ar3 each independently represent a phenyl or 5- or 6-membered monocyclic heteroaryl ring, or a bicyclic ring system consisting of a 5- or 6-membered carbocyclic or heterocyclic ring which is benz-fused or fused to a 5- or 6-membered monocyclic heteroaryl ring, said ring or ring system being optionally substituted; t is 0 or 1; L2 and L3 are linker radicals as defined in the description.

Abstract: Compounds of formula (I) are ligands of the melanin concentrating hormone-1 receptor (MCH-1R), useful in the treatment of diseases responsive to modulation of melanin concentrating hormone (MCH) activity, for example feeding disorders and diseases for which obesity is a risk factor (I): wherein ring B is selected from specific substituted phenyl or benz-fused 5 membered N-containing heterocycles defined in the specification; R, is attached to a ring carbon of ring B, and represents hydrogen, F, Cl, or —OCH3; X is ?CH— or ?N—; L, is —CH2— or —CH2CH2—; L2 is a bond, —CH2— or —CO—; R2 is H or C, —C3 alkyl, or —N(R2) L, —is selected from specific cyclic amino linker radicals as defined in the specification; ring A is selected from specific N-containing heterocyclic rings as defined in the specification.

Abstract: Y4 receptor agonists selective for the Y4 receptor over the Y1 and Y2 receptors are useful for treatment of conditions responsive to activation of Y4 receptors. The Y4 selective agonists (a) are PP-fold peptide or PP-fold peptide mimics which have C— and N-terminal sequence features as specified in the description or (b) have an covalent intramolecular link, or (c) comprise two covalently linked C-terminal Y4 receptor-recognition amino acid sequences each of which comprises the last four residues of a C-terminal receptor recognition sequence of the type (a) agonists.

Abstract: Y receptor agonists which are selective for Y2 and Y4 receptors over the Y1 receptor are useful for treatment of, for example obesity, are (a) PP-fold peptides or PP-fold peptides mimics which have (i) a C-terminal Y receptor-recognition amino acid sequence represented by —X-Thr-Arg-X3-Arg-Tyr-C(=0)NR1R2 wherein R1 and R1 are independently hydrogen or C1-C6 alkyl X is Val, Ile, Leu or Ala, and X3 is Gln or Asn, or a conservatively substituted variant thereof in which Thr is replaced by His or Asn and/or Tyr is replaced by Trp or Phe; and/or Arg is replaced by Lys, and (ii) an N-terminal Y receptor-recognition amino acid sequence represented by H2N—X1-Pro-X2—(Glu or Asp)—wherein X1 is not present or is amino acid residue, and X2 is Leu or Ser or conservative substitutions of Leu or Ser, or (b) the said comprise a C-terminal Y receptor-recognition amino acid sequence as defined in (i) above, said Y receptor-recognition sequence being fused to an amphiphilic amino acid sequence domain comprising at least one alp

Abstract: The modified human PP peptides (i) [Lys4,Leu17,Ser30,Gln34]hPP, (ii) Lys4,Leu17,Thr30,Gln34]hPP; and (iii) [Lys4,Leu17,oxidised Met30,Gln34]hPP wherein “oxidised Met” may be the sulfoxide or sulfone, and certain analogues and derivativatised forms thereof as referred to in the specification, are selective agonists of the Y2 receptor relative to the Y1 and Y4 receptors, and are useful for, for example, appetite control and therapeutic angiogenesis.

Abstract: A pseudo-sequence method for comparing 7TM receptors with respect to the physicochemical properties of their binding sites, the method comprising the steps of: (i) optionally, aligning part of or all of the amino acid sequence of the first 7TM receptor with part of or all or the amino acid sequence of the one or more further 7TM receptors, (ii) selecting, in a sequential or non-sequential order, at the most 12 amino acid residues per helix and/or extracellular loops, which are involved in one or more binding sites of each 7TM receptor.

Abstract: Use of mutated ?-arrestin for an improved enzyme complementation assay or translocation assay, the improved enzyme complementation assay comprising: i) adding a substrate to a cell comprising a GPCR-EA fusion protein and a ?-arrestin-EB fusion protein, wherein the ?-arrestin is mutated, ii) adding a ligand to obtain, if possible, a GPCR-EA/?-arrestin-EB complex, and iii) measuring a signal arising from association of EA and EB to create an enzymatically active protein catalyzing conversion of the substrate which leads to a detectable signal, wherein the improvement leads to an increased signal compared with the signal obtained by use of the same process employing a ?-arrestin-EB fusion protein, wherein the ?-arrestin is wild type ?-arrestin, and the improved ?-arrestin translocation assay comprising i) providing a cell expressing a GPCR and comprising a ?-arrestin associated with an optically detectable molecule, ODM, wherein the ?-arrestin is mutated, ii) adding a ligand to obtain, if possible, a GPCR/?-arre

Abstract: A large depth of focus (DOF) display provides an image in which the apparent focus plane is adjusted to track an accommodation (focus) of a viewer's eye(s) to more effectively convey depth in the image. A device is employed to repeatedly determine accommodation as a viewer's gaze within the image changes. In response, an image that includes an apparent focus plane corresponding to the level of accommodation of the viewer is provided on the large DOF display. Objects that are not at the apparent focus plane are made to appear blurred. The images can be rendered in real-time, or can be pre-rendered and stored in an array. The dimensions of the array can each correspond to a different variable. The images can alternatively be provided by a computer controlled, adjustable focus video camera in real-time.