WO1999064407A1 - DERIVES D'ACIDE α-(1-PIPERAZINYL)ACETAMIDO ARENECARBOXYLIQUE UTILISES COMME ANTI-DIABETIQUES - Google Patents

DERIVES D'ACIDE α-(1-PIPERAZINYL)ACETAMIDO ARENECARBOXYLIQUE UTILISES COMME ANTI-DIABETIQUES Download PDF

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Publication number
WO1999064407A1
WO1999064407A1 PCT/EP1998/003431 EP9803431W WO9964407A1 WO 1999064407 A1 WO1999064407 A1 WO 1999064407A1 EP 9803431 W EP9803431 W EP 9803431W WO 9964407 A1 WO9964407 A1 WO 9964407A1
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
aryl
compound
alkoxy
formula
Prior art date
Application number
PCT/EP1998/003431
Other languages
English (en)
Inventor
Gérard Moinet
Gérard Botton
Gérard Patereau
Liliane Doare
Micheline Kergoat
Didier Mesangeau
Donald D. Bierer
Original Assignee
Merck Patent Gmbh
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to FR9705849A priority Critical patent/FR2763334A1/fr
Priority to SK1859-2000A priority patent/SK18592000A3/sk
Priority to CN98814107A priority patent/CN1119338C/zh
Priority to RU2001101171/04A priority patent/RU2198881C2/ru
Priority to PL98344006A priority patent/PL344006A1/xx
Priority to CA002334558A priority patent/CA2334558A1/fr
Priority to BR9816021-4A priority patent/BR9816021A/pt
Priority to EP98939495A priority patent/EP1091947A1/fr
Application filed by Merck Patent Gmbh filed Critical Merck Patent Gmbh
Priority to JP2000553416A priority patent/JP2002517489A/ja
Priority to PCT/EP1998/003431 priority patent/WO1999064407A1/fr
Priority to HU0102006A priority patent/HUP0102006A3/hu
Priority to KR1020007013900A priority patent/KR20010052662A/ko
Priority to AU87989/98A priority patent/AU748712B2/en
Priority to UA2001010132A priority patent/UA56324C2/uk
Publication of WO1999064407A1 publication Critical patent/WO1999064407A1/fr
Priority to NO20006214A priority patent/NO20006214L/no

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/14—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D295/145—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/15—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
    • C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
    • C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
    • C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
    • C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Definitions

  • the present invention relates to new ⁇ -(1-piperazinyl)acetamido arenecarboxylic acid derivatives which are useful in the treatment of diabetes.
  • Ar is selected from
  • - a mono-, bi- or tricyclic aryl group having from 6 to 14 carbon atoms, - a heteroaromatic group selected from the pyridyl, pyrimidinyl, pyrrolyl, furyl, thienyl, quinolyl, indolyl, benzothienyl, benzofuryl, benzopyranyl, benzothiopyranyl, dibenzofuryl, carbazolyl and benzothiazinyl groups, it being possible for the Ar group to carry 1 to 3 substituents selected from a C ⁇ -C 8 alkyl, (C 3 -C 8 )cycloalkyl(C ⁇ -C 6 )alkyl, d-C 8 alkoxy, (C 3 - C 8 )cycloalkyloxy(C 1 -C 6 )alkyl, (C3-C 8 )cycloalkyl(C ⁇ -C 6 )alkoxy(C ⁇ -C 6 )alkyl, (
  • R 4 , R 5 and R 6 are selected, independently of one another, from
  • the C ⁇ -C 8 alkyl groups can be linear or branched Mention may be ⁇ made, as examples, of the methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert- butyl and pentyl groups
  • the C ⁇ -C 8 alkoxy groups can likewise be linear or branched Mention may be made, as examples, of the methoxy ethoxy, propoxy isopropoxy, butoxy and isobutoxy groups 0
  • the halogens can be selected from fluorine, chlorine, bromine and iodine
  • heteroaryl groups in the definition of R ⁇ R 2 and R 3 may be defined in particular as defined for the heteroaromatic groups in the definition of Ar
  • the invention also relates to the tautomeric forms and to the enantiomers, diastereoisomers and epimers of the compounds of general formula (I)
  • the compounds of general formula (I) possess a carboxylic acid functional group and can be sa fied, then existing in the form of salts with bases o Examples of salts with bases of the compounds of general formula
  • (I) include the pharmacologically acceptable salts, such as the sodium salts potassium salts, calcium salts and other salts of the same type
  • the compounds of general formula (I) can also be sahfied with amines in order to form pharmaceutically acceptable salts
  • the compounds of general formula (I) could be sahfied with glucamine, N- methylglucamine, N,N-d ⁇ methylglucam ⁇ ne, ethanolamme, morpholine N-methylmorpholine or lysine
  • the compounds of general formula (I) possess basic nitrogen atoms and can be monosalified or disalified with inorganic or organic acids )
  • salts with acids of the compounds of general formula (I) include the pharmaceutically acceptable salts, such as, and non-exhaustively, the hydrochlonde, the hydrobromide, the sulphate, the succmate, maleate, fumarate malate or tartrate and the sulphonates, such as the methanesulphonate, the be ⁇ zenesulphonate or the toluenesulphonate.
  • the invention also relates to a process for the preparation of the compounds of general formula (I).
  • a preparation process according to the invention comprises the reaction of an aromatic amine of general formula (II):
  • R 7 is a hydrogen atom, a d-C 6 alkyl group or a benzyl group, with a haloacyl halide of general formula (III):
  • Hal represents a chlorine or bromine atom, in order to form a compound of general formula (IV):
  • R 7 is an alkyl group
  • the compound of general formula (VI) can be hydrolysed by conventional acidic or basic means in order to give the compound of general formula (I)
  • the compound of general formula (VI) can be hydrogenolysed in the presence of a catalyst, such as palladium-on-charcoal, in order to give the compound of general formula (I)
  • the compounds of formula (V) can be prepared as described by R Ratouis et al (J Med Chem , 8, 104, 1965) or by Prelog et al (Collection 0 Czechoslov Chem Communications, 6, 211 , 1934)
  • the compound (VI), in which R 7 is an alkyl group can by hydrolysed in the presence of a basic agent, such as dilute sodium hydroxide
  • a basic agent such as dilute sodium hydroxide
  • the enantiomers of the compounds of formula (I) can be separated by successive recrystallization of the salt of the acid (I) with an optically active base in solvents such as acetone, ethyl acetate or isopropanol and then displacement from the salt into an optically active acid by an inorganic or organic acid, according to a conventional method
  • the compounds according to the present invention can be used in the treatment of diabetes, in particular of non-insu n-dependent diabetes, because of their hypoglycaemic effect and of their absence of toxicity at the active doses
  • Another subject of the present invention is thus pharmaceutical compositions comprising an effective amount of a compound according to the invention
  • compositions according to the invention can be presented in forms intended for parenteral, oral rectal, permucosal or 5 percutaneous administration
  • excipients which are suitable for such administrations are derivatives of cellulose or microcrystalhne cellulose, alkaline-earth metal carbonates, magnesium phosphate, starches, modified starches or lactose for the solid forms Cocoa butter or polyethylene glycol stearates are the preferred excipients for rectal use
  • the dosage can vary within wide limits depending on the o therapeutic indication and the administration route, as well as the age and weight of the patient.
  • the following examples illustrate the preparation of the compounds of formula (I) and of the intermediates of formulae (II) and (IV).
  • the apparatus is placed under a hydrogen atmosphere and agitated at room temperature for 3 hours.
  • the anti-diabetic activity of the compounds of formula (I) by the oral route was determined with respect to an experimental model of non-insu n- dependent diabetes induced in the rat by streptozotocm
  • the non-insulm-dependent diabetes model is obtained in the rat by a neonatal (the day of birth) injection of streptozotocm
  • the diabetic rats used are 8 weeks old The animals are kept, from the day of their birth to the day of the experiment, in an animal house at a temperature regulated from 21 to 22°C and subject to a fixed cycle of light (from 7 h to 19 h) and of darkness (from 19 h to 7 h)
  • Their feeding consisted of a maintenance diet, water and food was supplied "ad libitum", except for fasting for 2 hours before the test when the food is withdrawn (post-absorptive state)
  • the rats are treated orally during the day with the test product Two hours after the final administration of the product and 30 minutes after anaesthetizing the animals with sodium pentobarbital (Nembutal ), a 300 ⁇ l blood sample is taken from the end of the tail

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Cette invention a trait à des composés correspondant à la formule générale (I) utilisés dans le traitement du diabète.
PCT/EP1998/003431 1997-05-13 1998-06-08 DERIVES D'ACIDE α-(1-PIPERAZINYL)ACETAMIDO ARENECARBOXYLIQUE UTILISES COMME ANTI-DIABETIQUES WO1999064407A1 (fr)

Priority Applications (15)

Application Number Priority Date Filing Date Title
FR9705849A FR2763334A1 (fr) 1997-05-13 1997-05-13 Derives anthraniliques
EP98939495A EP1091947A1 (fr) 1998-06-08 1998-06-08 Derives d'acide alpha-(1-piperazinyl)acetamido arenecarboxylique utilises comme anti-diabetiques
RU2001101171/04A RU2198881C2 (ru) 1998-06-08 1998-06-08 α-(1-ПИПЕРАЗИНИЛ)АЦЕТАМИДОПРОИЗВОДНЫЕ АРЕНКАРБОНОВОЙ КИСЛОТЫ, СПОСОБ ИХ ПОЛУЧЕНИЯ, ФАРМАЦЕВТИЧЕСКИЕ КОМПОЗИЦИИ, СПОСОБЫ ЛЕЧЕНИЯ
PL98344006A PL344006A1 (en) 1998-06-08 1998-06-08 Α-(1-piperazinyl)acetamido arenecarboxylic acid derivatives as antidiabetic agents
JP2000553416A JP2002517489A (ja) 1998-06-08 1998-06-08 抗糖尿剤としてのα−（１−ピペラジニル）アセトアミドアレーンカルボン酸誘導体
BR9816021-4A BR9816021A (pt) 1997-05-13 1998-06-08 Derivados de ácido alfa-(1-piperazinil) acetamido areno carboxilìco como agentes antidiabéticos
CN98814107A CN1119338C (zh) 1997-05-13 1998-06-08 用作抗糖尿病剂的α－(1－哌嗪基)乙酰氨基芳烃羧酸衍生物
SK1859-2000A SK18592000A3 (sk) 1998-06-08 1998-06-08 Derivát alfa-(1-piperazinyl)acetamidoarénkarboxylovej kyseliny, spôsob jeho prípravy a farmaceutický prostriedok, ktorý ho obsahuje
CA002334558A CA2334558A1 (fr) 1998-06-08 1998-06-08 Derives d'acide .alpha.-(1-piperazinyl)acetamido arenecarboxylique utilises comme anti-diabetiques
PCT/EP1998/003431 WO1999064407A1 (fr) 1997-05-13 1998-06-08 DERIVES D'ACIDE α-(1-PIPERAZINYL)ACETAMIDO ARENECARBOXYLIQUE UTILISES COMME ANTI-DIABETIQUES
HU0102006A HUP0102006A3 (en) 1998-06-08 1998-06-08 Alpha-(1-piperazinyl)acetamido arenecarboxylic acid derivatives medicaments comprising them and their use
KR1020007013900A KR20010052662A (ko) 1998-06-08 1998-06-08 항당뇨병제로서의 α-(1-피페라지닐)아세트아미도아렌카르복실산 유도체
AU87989/98A AU748712B2 (en) 1998-06-08 1998-06-08 Alpha-(1-piperazinyl)acetamido arenecarboxylic acid derivatives as antidiabetic agents
UA2001010132A UA56324C2 (uk) 1998-06-08 1998-08-06 ПОХІДНІ <font face="Symbol">a</font>-(1-ПІПЕРАЗИНІЛ)АЦЕТАМІДОАРЕНКАРБОНОВИХ КИСЛОТ, СПОСІБ ЇХ ОТРИМАННЯ ТА ФАРМАЦЕВТИЧНА КОМПОЗИЦІЯ
NO20006214A NO20006214L (no) 1998-06-08 2000-12-07 <alfa>-(1-piperaziny1)acetamidoarenkarboksylsyrederivater som antidiabetiske midler

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
FR9705849A FR2763334A1 (fr) 1997-05-13 1997-05-13 Derives anthraniliques
PCT/EP1998/003431 WO1999064407A1 (fr) 1997-05-13 1998-06-08 DERIVES D'ACIDE α-(1-PIPERAZINYL)ACETAMIDO ARENECARBOXYLIQUE UTILISES COMME ANTI-DIABETIQUES

Publications (1)

Publication Number Publication Date
WO1999064407A1 true WO1999064407A1 (fr) 1999-12-16

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Family Applications (1)

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PCT/EP1998/003431 WO1999064407A1 (fr) 1997-05-13 1998-06-08 DERIVES D'ACIDE α-(1-PIPERAZINYL)ACETAMIDO ARENECARBOXYLIQUE UTILISES COMME ANTI-DIABETIQUES

Country Status (4)

Country Link
CN (1) CN1119338C (fr)
BR (1) BR9816021A (fr)
FR (1) FR2763334A1 (fr)
WO (1) WO1999064407A1 (fr)

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002081460A1 (fr) * 2001-04-06 2002-10-17 Janssen Pharmaceutica N.V. Biphenylcarboxamides hypolipidemiants
WO2003053366A2 (fr) * 2001-12-20 2003-07-03 Osi Pharmaceuticals, Inc. Composes pyrimidine antagonistes selectifs des recepteurs a2b, leur synthese et leur utilisation
WO2004050650A1 (fr) * 2002-11-27 2004-06-17 Bayer Pharmaceuticals Corporation Derives d'anilino-pyrazole utilises dans le traitement des diabetes
WO2006085112A1 (fr) * 2005-02-14 2006-08-17 Smithkline Beecham Corporation Derives de l'acide anthranilique comme agonistes du recepteur hm74a
US7429574B2 (en) 1998-06-02 2008-09-30 Osi Pharmaceuticals, Inc. 4-heterocyclo-pyrrolo[2,3d] pyrimidine compositions and their use
CN100448869C (zh) * 2002-11-27 2009-01-07 拜尔药品公司 用于治疗糖尿病的苯胺基吡唑衍生物
US7504407B2 (en) 2001-11-30 2009-03-17 Osi Pharmaceuticals, Inc. Compounds specific to adenosine A1 and A3 receptors and uses thereof
US7598252B2 (en) 2000-12-01 2009-10-06 Osi Pharmaceuticals, Inc. Compounds specific to adenosine A, receptors and uses thereof
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
US20220330591A1 (en) * 2018-08-10 2022-10-20 Firmenich Incorporated Antagonists of t2r54 and compositions and uses thereof
US11926616B2 (en) 2018-03-08 2024-03-12 Incyte Corporation Aminopyrazine diol compounds as PI3K-γ inhibitors

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0319124D0 (en) * 2003-08-14 2003-09-17 Smithkline Beecham Corp Chemical compounds
CN103804362A (zh) * 2012-11-12 2014-05-21 韩文毅 一类治疗糖尿病的化合物及其用途

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE850709A (fr) * 1976-02-02 1977-05-16 Lafon Labor Acetanilido-piperazines
FR2693722A1 (fr) * 1992-07-16 1994-01-21 Meram Lab Dérivés de la N-cycloalkylpipérazine, procédé d'obtention et compositions pharmaceutiques les contenant.
EP0638568A1 (fr) * 1993-07-23 1995-02-15 Adir Et Compagnie Pipérazines substituées, leur procédé de préparation et les compositions pharmaceutiques les contenant
WO1996026924A1 (fr) * 1995-02-28 1996-09-06 Suntory Limited Derives d'arylpiperidine et d'arylpiperazine et medicaments contenant lesdits derives
WO1998027078A1 (fr) * 1996-12-18 1998-06-25 Merck Patent Gmbh Nouveaux derives d'acide 4-(1-piperazinyl)benzoique, leur procede de production et leurs applications therapeutiques

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2674522B1 (fr) * 1991-03-26 1993-07-16 Lipha Nouveaux derives de l'indole, procedes de preparation et medicaments les contenant.

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE850709A (fr) * 1976-02-02 1977-05-16 Lafon Labor Acetanilido-piperazines
FR2693722A1 (fr) * 1992-07-16 1994-01-21 Meram Lab Dérivés de la N-cycloalkylpipérazine, procédé d'obtention et compositions pharmaceutiques les contenant.
EP0638568A1 (fr) * 1993-07-23 1995-02-15 Adir Et Compagnie Pipérazines substituées, leur procédé de préparation et les compositions pharmaceutiques les contenant
WO1996026924A1 (fr) * 1995-02-28 1996-09-06 Suntory Limited Derives d'arylpiperidine et d'arylpiperazine et medicaments contenant lesdits derives
WO1998027078A1 (fr) * 1996-12-18 1998-06-25 Merck Patent Gmbh Nouveaux derives d'acide 4-(1-piperazinyl)benzoique, leur procede de production et leurs applications therapeutiques

Cited By (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7429574B2 (en) 1998-06-02 2008-09-30 Osi Pharmaceuticals, Inc. 4-heterocyclo-pyrrolo[2,3d] pyrimidine compositions and their use
US7598252B2 (en) 2000-12-01 2009-10-06 Osi Pharmaceuticals, Inc. Compounds specific to adenosine A, receptors and uses thereof
CN1312140C (zh) * 2001-04-06 2007-04-25 詹森药业有限公司 降低脂质的联苯基甲酰胺
US7642378B2 (en) 2001-04-06 2010-01-05 Janssen Pharmaceutica Nv Lipid lowering biphenylcarboxamides
WO2002081460A1 (fr) * 2001-04-06 2002-10-17 Janssen Pharmaceutica N.V. Biphenylcarboxamides hypolipidemiants
US7504407B2 (en) 2001-11-30 2009-03-17 Osi Pharmaceuticals, Inc. Compounds specific to adenosine A1 and A3 receptors and uses thereof
US6916804B2 (en) 2001-12-20 2005-07-12 Osi Pharmaceuticals, Inc. Pyrimidine A2b selective antagonist compounds, their synthesis and use
WO2003053366A3 (fr) * 2001-12-20 2004-01-29 Osi Pharm Inc Composes pyrimidine antagonistes selectifs des recepteurs a2b, leur synthese et leur utilisation
WO2003053366A2 (fr) * 2001-12-20 2003-07-03 Osi Pharmaceuticals, Inc. Composes pyrimidine antagonistes selectifs des recepteurs a2b, leur synthese et leur utilisation
EA007468B1 (ru) * 2001-12-20 2006-10-27 Оси Фармасьютикалз, Инк. Пиримидиновые соединения, относящиеся к a-селективным антагонистам, их синтез и применение
EA011809B1 (ru) * 2001-12-20 2009-06-30 Оси Фармасьютикалз, Инк. Пиримидиновые соединения, их применение в качестве a-селективных антагонистов и способ их получения
US7501407B2 (en) 2001-12-20 2009-03-10 Osi Pharmaceuticals, Inc. Pyrimidine A2B selective antagonist compounds, their synthesis and use
AU2002366811B2 (en) * 2001-12-20 2009-01-15 Osi Pharmaceuticals, Inc. Pyrimidine A2B selective antagonist compounds, their synthesis and use
CN100448869C (zh) * 2002-11-27 2009-01-07 拜尔药品公司 用于治疗糖尿病的苯胺基吡唑衍生物
WO2004050650A1 (fr) * 2002-11-27 2004-06-17 Bayer Pharmaceuticals Corporation Derives d'anilino-pyrazole utilises dans le traitement des diabetes
WO2004050651A1 (fr) * 2002-11-27 2004-06-17 Bayer Pharmaceuticals Corporation Derives d'anilinopyrazole destines au traitement du diabete
US7265144B2 (en) 2002-11-27 2007-09-04 Bayer Pharmaceuticals Corporation Anilinopyrazole derivatives useful for the treatment of diabetes
WO2006085112A1 (fr) * 2005-02-14 2006-08-17 Smithkline Beecham Corporation Derives de l'acide anthranilique comme agonistes du recepteur hm74a
US11926616B2 (en) 2018-03-08 2024-03-12 Incyte Corporation Aminopyrazine diol compounds as PI3K-γ inhibitors
US11046658B2 (en) 2018-07-02 2021-06-29 Incyte Corporation Aminopyrazine derivatives as PI3K-γ inhibitors
US20220330591A1 (en) * 2018-08-10 2022-10-20 Firmenich Incorporated Antagonists of t2r54 and compositions and uses thereof
US11871772B2 (en) * 2018-08-10 2024-01-16 Firmenich Incorporated Antagonists of T2R54 and compositions and uses thereof

Also Published As

Publication number Publication date
CN1301259A (zh) 2001-06-27
BR9816021A (pt) 2001-05-15
CN1119338C (zh) 2003-08-27
FR2763334A1 (fr) 1998-11-20

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