86 results about "S1P Receptor" patented technology

Provided are: a compound represented by formula (I):(wherein ring A and ring D each represent a cyclic group which may have a substituent(s); E and G each represent a bond or a spacer having 1 to 8 atoms in its main chain; L represents a hydrogen atom or a substituent; X represents amino which may have a substituent(s), or a heterocyclic group which contains at least one nitrogen atom and which may have a substituent(s); n represents 0 to 3, in which when n is 2 or more, a plurality of ring A's may be the same or different from one another); a salt thereof; an N-oxide form thereof; a solvate thereof, a prodrug thereof; and a medicament which includes those. The compound represented by formula (I) is capable of binding S1P receptors (in particular, EDG-1 and / or EDG-6), and useful for preventing and / or treating rejection in transplantation, autoimmune diseases, allergic diseases, etc.

A compound having an ability to bind to an S1P receptor (particularly EDG-6, preferably EDG-1 and EDG-6), for example, the compound represented by formula (I) of the present invention, a salt thereof, a solvate thereof or a prodrug thereof is useful for prevention and / or treatment of rejection of transplantation, graft-versus-host disease, autoimmune disease, allergic disease and the like. wherein ring A is a cyclic group; ring B is a cyclic group which may have substituent(s); X is a spacer having 1 to 8 atoms in its main chain, etc.; Y is a spacer having 1 to 10 atoms in its main chain, etc.; n is 0 or 1, wherein when n is 0, m is 1 and R1 is a hydrogen atom or a substituent, and wherein when n is 1, m is 0 or an integer of 1 to 7 and R1 is a substituent, and wherein m is 2 or more, R1s are the same or different.

The present invention encompasses compounds of Formula I: (I) as well as the pharmaceutically acceptable salts thereof. The compounds are useful for treating immune mediated diseases and conditions, such as bone marrow, organ and tissue transplant rejection. Pharmaceutical compositions and methods of use are included.

Provided are: a compound represented by formula (I):(wherein ring A and ring D each represent a cyclic group which may have a substituent(s); E and G each represent a bond or a spacer having 1 to 8 atoms in its main chain; L represents a hydrogen atom or a substituent; X represents amino which may have a substituent(s), or a heterocylic group which contains at least one nitrogen atom and which may have a substituent(s); n represents 0 to 3, and when n is 2 or more, a plurality of ring A's may be the same or different from one another); a salt, an N-oxide form, a solvate, or a prodrug thereof; and a medicament which includes those. The compound of formula (I) is capable of binding S1P receptors (in particular, EDG-1 and / or EDG-6), and useful for preventing and / or treating rejection in transplantation, autoimmune diseases, allergic diseases, etc.

To provide an amino phosphate derivative having an excellent sphingosine-1-phosphate (S1P) receptor modulatory action.As a result of continued intensive research to create a highly safe compound which has an S1P receptor modulatory action, is has been discovered that an amino phosphate derivative represented by the following general formula (1),has a strong S1P receptor modulatory action.

The present invention is directed to novel, potent, and selective agents, which are agonists or antagonists of the one or more of the individual receptors of the S1P receptor family. The compounds of the invention are useful as therapeutics for treating medical conditions associated with agonism or antagonism of the individual receptors of the S1P receptor family.

The present invention relates to a compound represented by the formula (I), a salt thereof, an N-oxide form thereof, a solvate thereof, or a prodrug thereof, and a medicament containing the same. The compound represented by the formula (I) has an ability to bind to an S1P receptor (particularly, EDG-1, EDG-6, and / or EDG-8) and is useful for preventing and / or treating for rejection to transplantation, graft-versus-host disease, autoimmune diseases, allergic diseases, neurodegenerating diseases, and the like.wherein all symbols are described in the specification.

The present invention encompasses compounds of Formula (I): as well as the pharmaceutically acceptable salts thereof. The compounds are useful for treating immune mediated diseases and conditions, such as bone marrow, organ and tissue transplant rejection. Pharmaceutical compositions and methods of use are included.

The invention provides compositions and methods useful for treating wounds and enhancing wound healing. The present invention discloses a continuous polymer coating system to provide sustained localized delivery of bioactive agents. The data demonstrate the efficacy of a bioactive coating comprising the polymer PLAGA and the agent FTY720, a selective agonist for sphingosine 1-phosphate receptors, and biologically active derivatives and analogs thereof, for use in wound healing. In vitro drug release studies validated 64% loading efficiency with complete release of compound following 14 days. Mechanical evaluation of healing bone showed significant enhancement of mechanical stability in FTY720 treatment groups. Superior osseous integration across the host-graft interface, significant enhancement in smooth muscle cell investment, and reduction in leukocyte recruitment were evident in FTY720 treated groups. The present invention is useful for enhancing angiogenesis for wound healing.

The present invention relates to spiro-cyclic amine derivatives of the formula (I)whereinR1 is selected fromcyano,(2-4C)alkenyl, (2-4C)alkynyl, (1-4C)alkyl each optionally substituted with CN or one or more fluoro atoms,(3-6C)cycloalkyl, (4-6C)cycloalkenyl or a (8-10C)bicyclic group, each optionally substituted with halogen or (1-4C)alkyl,phenyl, biphenyl, naphthyl, each optionally substituted with one or more substituents independently selected from halogen, cyano, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (1-6C)alkoxy optionally substituted with one or more fluoro atoms, amino, di(1-4C)alkylamino and (3-6C)cycloalkyl optionally substituted with phenyl which may be substituted with (1-4C)alkyl or halogen,phenyl substituted with phenoxy, benzyl, benzyloxy, phenylethyl or monocyclic heterocycle, each optionally substituted with (1-4C)alkyl optionally substituted with one or more fluoro atoms,monocyclic heterocycle optionally independently substituted with halogen, (1-6C)alkyl optionally substituted with one or more fluoro atoms, (3-6C)cycloalkyl, or phenyl optionally substituted with (1-4C)alkyl or halogen,andbicyclic heterocycle optionally substituted with halogen or (1-4C)alkyl optionally substituted with one or more fluoro atoms;—Y—(Cn-alkylene)-X— is a linking group whereinY is attached to R1 and selected from a bond, —O—, —CO—, —S—, —SO—, —SO2—, —NH—, —CH═CH—, —C(CF3)═CH—, —C≡C—, —CH2—O—, —O—CO—, —CO—O—, —CO—NH—, —NH—CO—, and trans-cyclopropylene;n is an integer from 0 to 10; andX is attached to the phenylene / pyridyl moiety and selected from a bond, —O—, —S—, —SO—, —SO2—, —NH—, —CO—, —CH═CH—, and trans-cyclopropylene;R2 is H or independently selected from one or more substituents selected from halogen, (1-4C)alkoxy and (1-4C)alkyl optionally substituted with one or more fluor atoms; andR3 is (1-4C)alkylene-R4 wherein the alkylene group may be substituted with one or more halogen atoms or with (CH2)2 to form a cyclopropyl moiety, or R3 is (3-6C)cycloalkylene-R4, —CH2-(3-6C)cycloalkylene-R4, (3-6C)cycloalkylene-CH2—R4 or —CO—CH2—R4, wherein R4 is —OH, —PO3H2, —OPO3H2, —COON, —COO(1-4C)alkyl or tetrazol-5-yl;Q is a bond or —O—;—W—T— is selected from —CH═CH—, —CH2—CH2—, —CH2—O—, —O—CH2—, —O—CH2—CH2—, and —CO—O—;R5 is H or independently selected from one or more halogens;Z is CH, CR2 or N; andA represents a morpholine ring structure or a 5-, 6- or 7-membered cyclic amine;or a pharmaceutically acceptable salt, a solvate or hydrate thereof or one or more N-oxides thereof.The compounds of the invention have affinity to S1P receptors and may be used in the treatment, alleviation or prevention of diseases and conditions in which (a) S1P receptor(s) is (are) involved.

The present invention relates to a stable pharmaceutical composition comprising an S1P receptor agonist and one or more pharmaceutically acceptable excipients, wherein the composition is free of a sugar alcohol. It also relates to method of preparing such compositions and using those compositions in the treatment of multiple sclerosis.

A method of treating a subject in need of a cell or tissue transplant is disclosed. The method comprising (a) transplanting a non-syngeneic cell or tissue transplant into the subject, wherein the transplant comprises bone marrow or lymphoid cells; and (b) administering to the subject a therapeutically effective amount of an immunosuppressive regimen comprising a Sphingosine 1-Phosphate Receptor Agonist, a B7 molecule inhibitor and a CD2 / CD58 pathway inhibitor, thereby treating the subject.

The present invention encompasses compounds of Formula I:as well as the pharmaceutically acceptable salts thereof. The compounds are S1P1 / Edg1 receptor agonists and thus have immunosuppressive, anti-inflammatory and hemostatic activities by modulating leukocyte trafficking, sequestering lymphocytes in secondary lymphoid tissues, and enhancing vascular integrity. The invention is also directed to pharmaceutical compositions containing such compounds and methods of treatment or prevention.

This invention relates to new fused heterocyclic derivatives having affinity to S1P receptors, a pharmaceutical composition containing said compounds, as well as the use of said compounds for the preparation of a medicament for treating, alleviating or preventing diseases and conditions in which any S1P receptor is involved or in which modulation of the endogenous S1P signaling system via any S1P receptor is involved.

The present invention relates to sphingosine-1-phosphate (S1P) receptors and compounds of the general formula:that are useful in the treatment and prevention of conditions associated with such receptors. More specifically, the present invention relates to the synthesis and use of sphingosine 1-phosphate receptor 2 (S1P2) antagonists that are useful in the treatment of cancer, atherosclerosis, diabetic retinopathy, and other inflammatory diseases. Among these inflammatory diseases that could be treated with these S1P2 antagonist are those characterized by fibrosis including chronic lung disease, chronic kidney and liver disease, chronic heart disease, and skin diseases such as sclerosis / scleroderma. The S1P2 antagonists can also be used in the treatment of glioblastoma multiforme (brain cancer), pediatric neuroblastoma, and other cancers.

S1P receptor modulators or agonists are administered following a dosage regimen whereby during the initial days of treatment the daily dosage is lower than the standard daily dosage.

The present invention relates to S1P analogs that have activity as S1P receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate S1P receptor activity. The compounds have the general structure: wherein R11 is C5-C18 alkyl or C5-C18 alkenyl; Q is C3-C6 optionally substituted cycloalkyl, C3-C6 optionally substituted heterocyclic, C3-C6 optionally substituted aryl C3-C6 optionally substituted heteroaryl or —NH(CO)—; R3 is H, C1-C4 alkyl, (C1-C4 alkyl)OH or (C1-C4 alkyl)NH2; R23 is H or C1-C4 alkyl, and R15 is hydroxy, phosphonate, or wherein X and R12 is O or S; or a pharmaceutically acceptable salt or tautomer thereof.

Agonist of vascular endothelial sphingosine-1-phosphate receptors are described. Compounds such as FTY720 can be phosphorylated by sphingosine kinase-2 into the phosphorylated froms which serve as sphingosine-1-phosphate receptor agonists. The vascular endothelial sphingosine-1-phosphate receptor agonists are employed in methods of treating a mammal for vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels. The sphingosine-1-phosphate receptor agonists can be used for the manufacture of a medicament for treating vascular permeability disorders and unwanted vascular endothelial cell apoptosis, and for the growth of new blood vessels.

The present invention provides a cell culture enriched for sphingolipid enhances neural stem cells (SENSe), particularly oligodendrocyte precursor cells (ODPCs), that do not form teratomas after transplanted in vivo. Methods for producing and use of the invention ODPCs or the cell culture enriched with these ODPCs for stem cell therapy are also provided. The invention method comprises culturing a stem cell culture with a cell culture medium comprising a ceramide compound and a S1P receptor agonist in sequence, overlapping intervals or concurrent manners. The present invention further provides a cellular or gene therapy using a composition comprising a ceramide compound in conjunction with a S1P1 agonist to proliferate or differentiate endogeneous neural stem cells to ODPCs and further to oligodendrocytes.

This invention is based on the discovery that the administration of a sphingosine-1-phosphate receptor antagonist (S1P) and at least one chemotherapeutic agent selected from the the group of antimicrotubule agents provides an unexpectedly superior treatment for cancer. Antimicrobial agents such as the taxane compounds are known in the art, for example, paclitaxel (available as TAXOL® from Bristol-Myers Squibb, Princeton, N.J.), docetaxel (available as TAXOTERE® from Sanofi-aventis, Bridgewater, N.J.) and the like and other compounds that act as antimicrotubule agents, such as Vincristine (ONCOVIN®, VINCASAR PFS®, VCR), Vinblastin (VELBAN®, VELSAR®) and Vinorelbine, and similar compounds. The present invention also provides methods of modulating the growth of selected cell populations, such as cancer cells, by administering a therapeutically effective amount of at least one sphingosine-1-phosphate 1 (S1P1R) receptor antagonists, and at least one antimicrotubule agent.

The present invention is directed to novel, potent, and selective agents, which are agonists or antagonists of the one or more of the individual receptors of the S1P receptor family. The compounds of the invention are useful as therapeutics for treating medical conditions associated with agonism or antagonism of the individual receptors of the S1P receptor family.