FGF21 ANALOGUES AND DERIVATIVES

Derivatives of Fibroblast Growth Factor 21 which have improved properties for treating diabetes can be prepared by a recombinant process. 1. [−1A , L166F , M168L , G174V , Y179F] FGF21 , analogues of [−1A , L166F , M168L , G174V , Y179F] FGF21 optionally containing one or more of the following amino acid substitutions (exchanges): 71C , 121Q , 173A and/or des181 , optionally , having up to four further mutations and/or , optionally , the 179 and/or 180 amino acid is not present and derivatives of such analogues containing Cys in position 71 which derivatives have a group of the general formula HOOC—(CH) , —CONH—CH(COOH)—CH—CH—CONH—(CHCHO)—CH—CONH—(CHCHO)—CH—CONH—(CH)—NHCO—CH— (modifying moiety) , wherein n is an integer in the range 10-20 , m is an integer in the range 1-3 , p is an integer in the range 1-3 , and q is an integer in the range 2-4 , covalently attached to the sulphur atom in the mercapto group present in the cysteine residue in position 71.2. [−1A , 71C , L166F , M168L , G174V , Y179F] FGF21 , analogues of [−1A , 71C , L166F , M168L , G174V , Y179F] FGF21 optionally containing one or more of the following amino acid substitutions (exchanges): 121Q , 173A and/or des181 , optionally , having up to four further mutations and/or , optionally , the 179 and/or 180 amino acid is not present and derivatives of such analogues which derivatives have a group of the general formula HOOC—(CH)—CONH—CH(COOH)—CH—CH—CONH—(CHCHO)—CH—CONH—(CHCHO)—CH—CONH—(CH)—NHCO—CH— (modifying moiety) , wherein n is an integer in the range 10-20 , m is an integer in the range 1-3 , p is an integer in the range 1-3 , and q is an integer in the range 2-4 , covalently attached to the sulphur atom in the mercapto group present in the cysteine residue in position 71 , according to the previous claim.3. The derivative according to claim 1 , wherein n is 14.4. The derivative according to claim 1 , wherein n is 16.5. The derivative according to claim 1 , wherein n is 18.6. The derivative ...

Protease Stabilized, Pegylated Insulin Analogues

Novel PEGylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H. The PEGylation is at B29K.

Insulin derivatives

N -terminally modified insulin derivatives

The invention is related to novel N-terminally modified insulin derivatives comprising extra disulphide bond(s), pharmaceutical compositions comprising such and methods of making such.

Protease stabilized, acylated insulin analogues

Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.

Protease stabilized, acylated insulin analogues

Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.

Protease stabilized, acylated insulin analogues

Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.

Protease-stabilized acylated insulin analogues.

Method of acylating a peptide or protein

A method for selectively acylating an amino group in a peptide or protein which has two or more reactive nucleophilic functional groups is described.

Fgf21 analogues and derivatives

Derivatives of Fibroblast Growth Factor 21 which have improved properties for treating diabetes can be prepared by a recombinant process.

N-terminal modified fgf21 compounds

Analogues of FGF21 carrying a modifying, substituted ethylene or benzyl group can be used for treatment or prevention of diabetes, dyslipidemia, obesity, cardiovascular diseases, metabolic syndrome, and/or Non Alcoholic Fatty Liver Disease (NAFLD).

Multi substituted insulins

The present invention regards an insulin derivative comprising at least 2 albumin binding moieties, wherein said albumin binding moieties comprise fatty diacid substitutions and a method for preparing such an insulin derivative by acylation and/or reductive alkylation. The present invention also concern a pharmaceutical cpmrising such an insulin derivative.

Method of acylating a peptide or protein

A method has for selectively acylating an amino group in a peptide or protein which has two or more reactive nucleophilic functional groups is described.

Condensed 1,2,4-thiadiazine and condensed 1,4-thiazine derivatives, their preparation and use

Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives, their preparation and use

1,2,4-thiadiazine and 1,4-thiazine derivatives represented by formula (I) wherein A, B, D, R1, R2, R3 and R4 are defined in the description, compositions thereof and methods for preparing the compounds are described. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

Fgf21 derivatives and uses thereof

The invention relates to a derivative of a FGF21 protein having a cysteine residue at a position corresponding to position 167, 169, 170, 171, 172, 173, 174, 175 and in particular position 180 or position 181 of mature human FGF21 and derivatives thereof having a side chain attached to this cysteine. The FGF21 derivatives of the invention display high potency towards the FGF receptors. The invention also relates to pharmaceutical compositions comprising such FGF21 derivatives and pharmaceutically acceptable excipients, as well as the medical use of the FGF21 derivatives.

Acylated single chain insulin

The invention is related to an acylated, single-chain insulin comprising the B- and the A-chain of human insulin or an analogue thereof connected by a connecting peptide, wherein a lysine residue being substituted for the natural amino acid residue in at least one of the positions A8, A9 or A10 in the human insulin A-chain is chemically modified by acylation.

Hitherto unknown insulin derivatives

INSULIN DERIVATIVES

Un derivado insulínico comprendiendo una insulina progenitora y un sustituyente, donde el sustituyente es unido bien a un grupo ε-amino de un residuo de Lys presente en la cadena A de la insulina progenitora en la posición A8, A9; A10; A12; A14; A15; A17; A18; A21; A22; A23 o A24 o a un grupo ε-amino de un residuo de Lys en la cadena B de la insulina progenitora en la posición B1, B2, B3, B4; B20; B21 o B22 a condición que cuando B3 es Lys, entonces B29 no sea Glu, donde el sustituyente es de fórmula general: -W-X-Y-ZdondeW es: - un residuo de α-aminoácido con un grupo de ácido carboxílico en la cadena lateral cuyo residuo forma, con uno de sus grupos de ácido carboxílico, un grupo amida con el grupo ε-amino de un residuo de Lys presente en la cadena A o B de la insulina progenitora; o - una cadena compuesta por dos, tres o cuatro residuos de α-aminoácido unidos entre sí por medio de enlaces de amida, esta cadena, por medio de un enlace amida, se une al grupo ε-amino de un residuo de Lys presente en la cadena A o B de la insulina progenitora, los residuos de aminoácidos de W estando seleccionados del grupo de residuos de aminoácidos con una cadena lateral neutra y residuos de aminoácidos con un grupo de ácido carboxílico en la cadena lateral de modo que W tiene al menos un residuo de aminoácido que tiene un grupo de ácido carboxílico en la cadena lateral; o - un enlace covalente de X al grupo ε-amino de un residuo de Lys presente en la cadena A o B de la insulina progenitora; X es: - -CO; --CH(COOH)CO-; - -CON(CH2COOH)CH2CO-; - -CON(CH2COOH)CH2CON(CH2 COOH)CH2CoO - -CON(CH2CH2COOH)CH2CH2O; - -CON(CH2CH2COOH)CH2CH2CON(CH2 CH2 COOH)CH2CH2CO; - -CONHCH(COOH)(CH2)4NHCO-; - -CON(CH2CH2COOH)CH2CO-; o - -CON(CH2COOH)CH2 CH2CO A condición que a) cuando W es un residuo de aminoácido o una cadena de residuos de aminoácidos, el carbono del carbonilo subrayado en X forma un enlace amida con un grupo amino en W, o b) cuando W es un enlace covalente, el carbono del carbonilo ...

Novel insulin derivatives

The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula:          -W-X-Y-Z wherein W, X, Y and Z are as defined in the disclosure.

Fused 1,2,4-thiadiazine derivatives, their preparation, their use and pharmaceutical compositions containing them

A jelen találmány tárgyát 1,2,4-tiadiazin-származékok, az ezenvegyületek előállítására szolgáló eljárások, valamint az ezenvegyületeket tartalmazó összetételek képezik. A találmány tárgyátképezi továbbá ezen vegyületek alkalmazása gyógyszerek előállításánál,illetve terápiás célokra történő felhasználása. A találmány szerintivegyületek különösen alkalmasak például a központi idegrendszer, aszív- és érrendszer, a légzőszervek, az emésztőrendszer és ahormonrendszer betegségeinek, a vázizom csökkent vérkeringésével járóbetegségek, a koraszülés és a menstruációs zavarok, a kopaszságvalamint a vizelettartási nehézségek kezelésében. A találmány szerintielőnyös vegyületek tieno[3,2-e][1,2,4]-tiadiazin-1,1-dioxid-származékok. Ó The present invention relates to 1,2,4-thiadiazine derivatives, processes for the preparation of these compounds, and compositions containing these compounds. The invention further relates to the use of these compounds in the manufacture of a medicament or for use in therapy. The compounds of the invention are particularly useful in the treatment of, for example, diseases of the central nervous system, ascites and the vascular system, respiratory, digestive and hormone systems, disorders of the circulatory system of the skeletal muscle, premature labor and menstrual disorders, and urinary incontinence. Preferred compounds of the invention are thieno [3,2-e] [1,2,4] thiadiazine 1,1-dioxide derivatives. HE

fgf21 derivatives and their use

a presente invenção refere-se a um derivado de uma proteína do fgf21 tendo um resíduo de cisteína em uma posição que corresponde à posição 167, 169, 170, 171, 172, 173, 174, 175 e em particular a posição 180 ou posição 181 do fgf21 humano maduro e seus derivados tendo uma cadeia lateral ligada à esta cisteína. os derivados de fgf21 da invenção apresentam alta potência para os receptores do fgf. a invenção também refere-se às composições farmacêuticas que compreendem tais derivados de fgf21 e excipientes farmaceuticamente aceitáveis, assim como o uso médico dos derivados de fgf21. The present invention relates to a derivative of an fgf21 protein having a cysteine residue at a position corresponding to position 167, 169, 170, 171, 172, 173, 174, 175 and in particular position 180 or position 181. of mature human gff21 and derivatives thereof having a side chain linked to this cysteine. The fgf21 derivatives of the invention have high potency for fgf receptors. The invention also relates to pharmaceutical compositions comprising such fgf21 derivatives and pharmaceutically acceptable excipients, as well as the medical use of fgf21 derivatives.

Derivatives of condensed 1,2,4-thiadiazine, their production and application

Pegylated extended insulins

Novel derivative of an insulin analogue.

La presente invención provee un nuevo derivado de un análogo de insulina humana, útil para el tratamiento de diabetes.

Novel derivative of an insulin analogue.

La presente invención se refiere a un nuevo derivado de un análogo de insulina humana, útil para el tratamiento de diabetes.

Protease stabilized, acylated insulin analogues

Novel insulin derivatives

Fused 1,4-thiazine-2-carbonitrile derivatives, their preparation and use

The present invention relates to fused 1,4-thiazine-2-carbonitrile derivatives, compositions thereof and methods for preparing the compounds. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives, their preparation and use

New insulin derivatives

Derivado de insulina de la des(B30) insulina humana que posee una cadena lateral fijada al grupo ε-amino de un residuo de Lys presente en la cadena B de des(B30) insulina humana, la cadena lateral tiene la fórmula general: -W-X-Y-Z donde W es: * un residuo de α-aminoácido con un grupo de ácido carboxílico en la cadena lateral, este aminoácido está seleccionado del grupo que consiste en "-Asp, -Asp, "-Glu, $-Glu, "-hGlu y %-hGlu y este residuo forma, con uno de sus grupos de ácido carboxílico, un grupo de amida con el grupo ε-amino de un residuo de Lys presente en la cadena B de la des(B30) insulina humana; X es: * -CO-; Y es: * -(CH2)m donde m es un número entero en el intervalo de 12 a 16; y Z es: * -COOH; y cualquier complejo Zn2+ de los mismos. Insulin derivative of human des (B30) insulin that has a side chain attached to the ε-amino group of a Lys residue present in the B chain of human des (B30) insulin, the side chain has the general formula: -WXYZ where W is: * an α-amino acid residue with a carboxylic acid group in the side chain, this amino acid is selected from the group consisting of "-Asp, -Asp," -Glu, $ -Glu, "-hGlu and % -hGlu and this residue forms, with one of its carboxylic acid groups, an amide group with the ε-amino group of a Lys residue present in the B chain of human des (B30) insulin; X is: * -CO-; Y is: * - (CH2) m where m is an integer in the range of 12 to 16; and Z is: * -COOH; and any Zn2 + complex thereof.

Novel insulin derivatives

The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula:          -W-X-Y-Z wherein W, X, Y and Z are as defined in the disclosure.

Insulin analogues with an acyl and aklylene glycol moiety

An acylated insulin analogue wherein the insulin analogue comprises a lysine residue connected C-terminally to the A21 amino acid residue or a peptide residue of up to 4 amino acid residues comprising a lysine residue which peptide residue is connected C-terminally to the A21 amino acid residue, characterized in that an acyl moiety comprising an alkylene glycol moiety is attached to the lysine residue in the A22 position or attached to a lysine residue present in the peptide residue that is attached to the C terminal end of the A21 amino acid residue and wherein there is only one lysine (K, Lys) in the insulin analogue, can conveniently be administered pulmonary.

Acylated insulin analogs, stabilized against proteases

Una insulina acilada estabilizada frente a proteasas en donde el resto acilo se fija a un residuo de lisina en la posición B29 de la insulina humana A14E, B16H, B25H, desB30, en donde dicha insulina acilada estabilizada frente a proteasas es insulina humana A14E, B16H, B25H, B29K(Nεeicosanodioil- γGlu-OEG-OEG), desB30. A protease stabilized acylated insulin where the acyl moiety binds to a lysine residue at position B29 of human insulin A14E, B16H, B25H, desB30, where said protease stabilized acylated insulin is human insulin A14E, B16H , B25H, B29K (Nεeicosanodioyl- γGlu-OEG-OEG), desB30.

Novel derivative of an insulin analogue

The present invention provides a novel derivative of an analogue of human insulin, useful for the treatment of diabetes.

Fused 1,2,4-thiadiazine derivatives, their preparation and use

1,2,4-Thiadiazine and 1,4-thiazine derivates represented by formula (I): wherein A, B, D, R 1 , R 2 , R 3 and R 4 are defined in the description, compositions thereof and methods for preparing the compounds are described. The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

Protease stabilized, acylated insulin analogues

Novel acylated insulin analogues exhibiting resistance towards proteases can, effectively, be administered pulmonary or orally. The insulin analogues contain B25H and A14E or A14H.

Insulin Derivatives

The present invention is related to insulin derivatives having a side chain attached to an ε-amino group of a Lys residue present in the A-chain or to an ε-amino group of a Lys residue in the B-chain.

Novel insulin derivatives

The present invention relates to insulin derivatives which are naturally occurring insulins or analogues thereof which have a side chain attached either to the a-amino group of the N-terminal amino acid residue of the B chain or to the e-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula: -W-X-Y-Z wherein W, X, Y and Z are as defined in the disclosure.

Pegylated, Extended Insulins

PEGylated, extended insulins are insulins which, compared with human insulin, has one or more extensions extended from the A1, B1, A21 and/or B30 position(s), said extension(s) consist(s) of amino acid residue(s) and wherein a PEG moiety, via a linker, is attached to one or more of the amino acid residues in the extension(s). PEG is polyethyleneglycol. Such PEGylated, extended insulins have higher bioavailability and a longer time-action profile than regulär insulin and are in particular suited for pulmonary administration and can, conveniently, be used to treat diabetes.

Indole derivatives for use as chemical uncoupler

Novel 3-vinylsulfonyl indole derivatives of formula (I) are chemical uncouplers useful e.g. for treatment of obesity.

Fgf21 derivatives and uses thereof.

La invención se relaciona con un derivado de una proteína FGF21 que tiene un residuo cisteína en una posición que corresponde a la posición 167, 169, 170, 171, 172, 173, 174, 175 y en particular la posición 180 o la posición 181 de FGF21 humano maduro y derivados de los mismos que tienen una cadena lateral unida a esta cisteína. Los derivados de FGF21 de la invención presentan una potencia elevada hacia los receptores de FGF. La invención también se relaciona con composiciones farmacéuticas que comprenden a estos derivados de FGF21 y a excipientes farmacéuticamente aceptables así como el uso médico de los derivados de FGF21.

Insulin analogues with an acyl and aklylene glycol moiety

Acylated single chain insulin

The invention is related to acylated, single-chain insulin comprising the B- and the A-chain of human insulin or an analogue thereof connected by a connecting peptide, wherein the natural amino acid residue in position B1 or a lysine residue being substituted for the natural amino acid residue in one of the positions B1, B2, B3 or B4 in the human insulin B-chain has been chemically modified by acylation.

Glucose sensitive insulin derivatives and uses thereof

The present invention relates to novel insulin derivatives and their use in the treatment or prevention of medical conditions relating to diabetes. The insulin derivatives are glucose sensitive and display glucose-sensitive insulin receptor binding. The invention also relates to novel intermediates. Finally, the invention provides a pharmaceutical composition comprising the insulin derivatives of the invention and the use of such a composition in the treatment or prevention of medical conditions relating to diabetes.

Protease stabilized, acylated insulin analogues

Fuzionált 1,2,4-tiadiazin- és fuzionált 1,4-tiazinszármazékok, azok előállítása és alkalmazása

A jelen találmány tárgyát az (I) általánős képletű fűziőnált 1,2,4-tiadiazőn- és fűziőnált 1,4-tiazin-származékők, azők előállításáraszőlgáló eljárásők, tővábbá a vegyületeket tartalmazógyógyszerkészítmények, ezeknek e vegyületeknek gyógyszerként történőalkalmazása és azők terápiás célú felhasználása példáűl a közpőntiidegrendszer, a szív- és érrendszer, a tüdő, a győmőr- és bélrendszervalamint az endőkrinőlógia (belső elválasztás) megbetegedéseinekkezelésében. Az (I) általánős képletben szereplő A, B, D, R1, R2, R3és R4 csőpőrtők jelentését a leírás definiálja. (I) ŕ

1,2,4-benzothiadiazine derivatives, their preparation and use

1,2,4-Benzothiadiazine derivatives represented by formulawherein D, R1, R2, R3, R4, R5, R12, R13, R14, R15 are defined in the description, composition thereof and methods for preparing the compounds are described.The compounds are useful in the treatment of diseases of the central nervous system, the cardiovascular system, the pulmonary system, the gastrointestinal system and the endocrinological system.

Insulin derivate

1, 2, 4-benzothiadiazine derivatives, their preparation and use.

1,2,4-benzotiadiazinderivater, deres fremstilling og anvendelse

1,2,4-benzotiadiazinderivater som har formel (I) b 12 hvor D, R1, R2, R3, R4, R5, R12, R13, R14 og R15 er definert i beskrivelsen, pre- parater derav og fremgangsmåter for fremstilling av forbindelsene er be- skrevet. Forbindelsene kan anvendes ved behandlingen av sykdommer i sentralner- vesystemet, det kardiovaskulære system, det pulmonale system, det gastrointes- tinale system og det endokrinologiske system.

Derivados 1,2,4- benzotiadiazina, su preparacion y usos.

SE DESCRIBEN DERIVADOS DE 1,2,4 - BENZOTIADIAZINAS REPRESENTADOS POR LA FORMULA (I) EN LA QUE D, R 1 , R 2 , R SUP,3 , R 4 , R 5 , R 12 , R 13 , R 14 , R15 REPRESENTAN LO DEFINIDO EN LA DESCRIPCION, COMPOSICIO NES DE LOS MISMOS Y METODOS PARA LA PREPARACION DE LOS COMPUESTOS. LOS COMPUESTOS SON UTILES EN EL TRATAMIENTO DE ENFERMEDADES DEL SISTEMA NERVIOSO CENTRAL, DEL SISTEMA CARDIOVASCULAR, DEL SISTEMA PULMONAR, DEL SISTEMA GASTROINTESTINAL Y DEL SISTEMA ENDOCRINO.

1,2,4-benzothiadiazinové deriváty, jejich příprava a použití

1,2,4-benzothiadiazin-derivate, ihre herstellung und verwendung

1,2,4-Benzotiadiazin-származékok,valamint ezeket tartalmazó gyógyászati készítmények

A találmány tárgyát képezik az új, (I) általánős képletű 1,2,4-benzőltiadiazin-származékők vagy ezek gyógyászatilag megfelelő savvalvagy bázissal képzett sói, vagy őptikai izőmerjei, vagy az őptikaiizőmerek elegyei, ideértve a racém elegyeket vagy taűtőmer alakőkatis. A találmány tárgyáhőz tartőznak e vegyületeket tartalmazó gyó-gyászati készítmények és a vegyület előállítására szőlgáló eljárás is.Az (I) általánős képletű vegyületek káliűmcsatőrna-nyitó hatástfejtenek ki, és így eredményesen alkalmazhatók a közpőnti idegrendszermegbetegéseinek, a szív- és érrendszer, a tüdő, a győmőr- ésbélrendszer, valamint az endőkrinőlógiai rendszer betegségeinekkezelésére. Az (I) általánős képletben a szűbsztitűensek jelentésetöbbek között a következő: R1 és R5 jelentése többek között egymástól függetlenül hidrőgénatőm,hidrőxil-, 1-6 szénatőmős alkőxi, 3-6 szénatőmős ciklőalkilcső-pőrtvagy 1-6 szénatőmős alkil-, 2-6 szénatőmős alkenil- vagy 2-6szénatőmős alkinilcsőpőrt, és R4 jelentése hidrőgénatőm, vagy R4 és R5 együttes jelentése az (I) általánős képlet 2-es és 3-ashelyzetében lévő atőmők közötti kettőskötés egyik kötése és R1jelentése a fentiekben megadőtt, vagy R4 és R1 együttes jelentése az (I) általánős képlet 3-as és 4-eshelyzetében lévő atőmők közötti kettős kötés egyik kötése és R5jelentése a fentiekben megadőttakkal azőnős, D jelentése -S(=O)2 vagy -S(=O)-, R2 jelentése többek között hidrőgénatőm, hidrőxil-, 1-6 szénatőmősalkőxi-, 3-6 szénatőmős ciklőalkilcsőpőrt, hidrőxil-, vagy 1-6szénatőmős alkil-, 2-6 szénatőmős alkenil- vagy 2-6 szénatőmősalkinilcsőpőrt, R3 jelentése többek között R8, -OR8, C(=X1OR8, biciklűsős alkil-,aril-, heterőaril-, aril-alkil- vagy heterőarilcsőpőrt, ahől aképletben R8 jelentése többek között hidrőgénatőm, 3-6 szénatőmősciklőalkil- vagy (3-6 szénatőmős ciklőalkil)-(1-6 szénatőmős alkil)-csőpőrt, egy vagy több heterőatőmőt tartalmazó 3-6-tagú telítettgyűrűrendszer, vagy egyenes vagy elágazó láncú 1-18 szénatőmősalkilcsőpőrt, X1 jelentése őxig ...

Fused 1,2,4-thiadiazine derivatives their preparation and use

Fused 1,2,4-thiadiazine and fused 1,4-thiazine derivatives their preparation and use.

Derivatives of 2,5- and 3,5-disubstituted anilines, their preparation and use.

Fusion compounds and uses thereof

The invention relates to fusion proteins comprising a GLP-1 polypeptide and an FGF21 polypeptide separated by spacers. The invention also relates to fusion compounds comprising the fusion proteins and at least one substituent. The invention also relates to the pharmaceutical use of the fusion compounds.

Derivados de uma proteína do fgf21 e uso terapêutico e/ou profilático dos mesmos

DERIVADOS DE FGF21 E SEU USO. A presente invenção refere-se a um derivado de uma proteína do FGF21 tendo um resíduo de cisteína em uma posição que corresponde à posição 167, 169, 170, 171, 172, 173, 174, 175 e em particular a posição 180 ou posição 181 do FGF21 humano maduro e seus derivados tendo uma cadeia lateral ligada à esta cisteína. Os derivados de FGF21 da invenção apresentam alta potência para os receptores do FGF. A invenção também refere-se às composições farmacêuticas que compreendem tais derivados de FGF21 e excipientes farmaceuticamente aceitáveis, assim como o uso médico dos derivados de FGF21.

FGF21 derivatives with albumin binder A-B-C-D-E- and their use

The present invention relates to Fibroblast Growth Factor 21 (FGF21), more in particular to derivatives of FGF21 compounds having an albumin binder of the formula A-B-C-D-E- covalently attached. The invention also relates to novel FGF21 analogues, as well as to the pharmaceutical use of these FGF21 derivatives and analogues, in particular for the treatment of diabetes, dyslipidemia, obesity, cardiovascular diseases, metabolic syndrome, and/or Non Alcoholic Fatty Liver Disease (NAFLD). The derivatives of the invention are protracted, e.g. capable of maintaining a low blood glucose level for a longer period of time, capable of increasing the in vivo half-life of FGF21, and/or result in a lower clearance of FGF21. The derivatives of the invention are preferably furthermore of an improved oxidative stability.