ES2551557T3 - Pirimidin-4-carboxamidas cíclicas como antagonistas del receptor CCR2 para el tratamiento de inflamaciones, asma y EPOC - Google Patents

Pirimidin-4-carboxamidas cíclicas como antagonistas del receptor CCR2 para el tratamiento de inflamaciones, asma y EPOC Download PDF

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ES2551557T3
ES2551557T3 ES09775212T ES09775212T ES2551557T3 ES 2551557 T3 ES2551557 T3 ES 2551557T3 ES 09775212 T ES09775212 T ES 09775212T ES 09775212 T ES09775212 T ES 09775212T ES 2551557 T3 ES2551557 T3 ES 2551557T3
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alkyl
alkylene
cycloalkyl
heterocyclyl
ring
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Heiner Ebel
Sara Frattini
Riccardo Giovannini
Christoph Hoenke
Thomas Trieselmann
Patrick Tielmann
Stefan Scheuerer
Silke Hobbie (Marie Katrin)
Frank Buettner
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Boehringer Ingelheim International GmbH
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Abstract

Un compuesto de fórmula (I),**Fórmula** en la que R1 es -L1-R7, y en la que L1 es un enlace o un grupo seleccionado entre metileno, etileno y etenileno, y en la que R7 es un anillo seleccionado entre ciclopropilo, ciclobutilo, ciclopentilo, ciclohexilo, cicloheptilo, pirrolidinilo, piperidinilo, azepanilo, tetrahidrofuranilo, tetrahidropiranilo, oxepanilo, fenilo, piridilo y furanilo, en la que L1, si es diferente de un enlace, está opcionalmente sustituido con uno o más grupos seleccionados entre metilo y etilo, en la que el anillo R7 está opcionalmente sustituido con uno o más grupos seleccionados entre -F, -Cl, -metilo, -etilo, -propilo, -i-propilo, -ciclopropilo, -t-butilo, -CF3, -O-CF3, -CN, -O-metilo, -furanilo y -fenilo, en donde dicho furanilo y dicho fenilo están sustituidos, opcionalmente de manera independiente, con uno o más grupos seleccionados entre - alquilo C1-C6, halógeno, -OCH3, -CF3 y -OCF3, o en la que R7 está sustituido bi-valentemente con uno o más grupos seleccionados de entre en dos átomos del anillo vecinos de modo que se forma un anillo reasociado; en donde R2 se selecciona entre -H, -halógeno, -CN, -O-alquilo C1-C4, -alquilo C1-C4, -CH>=CH2, -C-CH, -CF3, - OCF3, -OCF2H y -OCFH2; en donde R3 se selecciona entre -H, -metilo, -etilo, -propilo, -i-propilo, -ciclopropilo, -OCH3 y -CN; en donde R4 y R5 se seleccionan independientemente entre un par de electrones, -H, y un grupo seleccionado entre -alquilo C1-C6, -NH2, -cicloalquilo C3-C8, -heterociclilo C3-C8, -arilo C5-C10, -heteroarilo C5-C10 y -C(O)-N(R8,R8'), donde R8 y R8' se seleccionan independientemente entre -H y -alquilo C1-C6, y en la que R4 y R5, si son distintos de un par de electrones o -H, están opcionalmente sustituidos independientemente con uno o más grupos seleccionados entre -halógeno, -OH, -CF3, -CN, -alquilo C1-C6, -O-alquilo C1-C6, -O-cicloalquilo C3-C8, -O-heterociclilo C3-C8, -O-arilo C5-C10, -O-heteroarilo C5-C10, -alquileno C0-C6-CN, -alquileno C0-C4-O-alquilo C1-C4, -alquileno C0-C4-O-cicloalquilo C3-C8, -alquileno C0-C4-O-heterociclilo C3-C8, - alquileno C0-C4-O-arilo C5-C10, -alquileno C0-C4-O-heteroarilo C5-C10, -alquileno C0-C4-Q-alquil C0-C4-N(R9,R9'), -alquileno C0-C4-N(R10)-Q-alquilo C1-C4, -alquileno C0-C4-N(R10)-Q-cicloalquilo C3-C8, -alquileno C0-C4-N(R10)-Qheterociclilo C3-C8, -alquileno C0-C4-N(R10)-Q-arilo C5-C10, -alquileno C0-C4-N(R10)-Q-heteroarilo C5-C10, -alquileno C0-C4-Q-N(R11,R11'), -alquileno C0-C4-N(R12)-Q-N(R13,R13'), -alquileno C0-C4 -R14, -alquileno C0-C4-Q-alquilo C1-C6, -alquileno C0-C4-Q-cicloalquilo C3-C8, -alquileno C0-C4-Q-heterociclilo C3-C8, -alquileno C0-C4-Q-arilo C5-C10, - alquileno C0-C4-Q-heteroarilo C5-C10, -alquileno C0-C4-O-Q-N(R15,R15') y -alquileno C0-C4-N(R16)-Q-O-(R17), en la que Q se selecciona entre -C(O)- y -SO2- en la que R12, R16 se seleccionan independientemente entre -H, -alquilo C1-C6 y -cicloalquilo C3-C6, en la que R9, R9', R10, R11, R11', R13, R13', R15, R15' se seleccionan independientemente entre -H, -alquilo C1-C6 y - cicloalquilo C3-C6, o en la que R9 y R9', R11 y R11', R13 y R13', R15 y R15' juntos forman un grupo -alquileno C2-C6, en la que R14 y R17 se seleccionan independientemente entre -H, -alquilo C1-C6, -arilo C5-C10, -heteroarilo C5-C10, - cicloalquilo C3-C8 y -heterociclilo C3-C8, donde dicho -heterociclilo C3-C8 comprende opcionalmente nitrógeno y/o - SO2- en el anillo, y donde R14 y R17 están opcionalmente sustituidos con uno o más grupos seleccionados entre -OH, -OCH3, -CF3, - OCF3, -CN, -halógeno, -alquilo C1-C4, >=O y -SO2-alquilo C1-C4, o en la que R4 y/o R5 son independientemente un grupo de la estructura -L2-R18, en la que L2 se selecciona entre -NH- y -N(alquilo C1-C4)-,~ en la que R18 se selecciona entre -arilo C5-C10, -heteroarilo C5-C10, -cicloalquilo C3-C8 y -heterociclilo C3-C8, en la que R18 está opcionalmente sustituido con uno o más grupos seleccionados entre halógeno, -CF3, -OCF3, -CN, -OH, -O-alquilo C1-C4, -alquilo C1-C6, -NH-C(O)-alquilo C1-C6, -N(alquil C1-C4)-C(O)-alquilo C1-C6, -C(O)-alquilo C1- C6, -S(O)2-alquilo C1-C6, -NH-S(O)2-alquilo C1-C6, -N(alquil C1-C4)-S(O)2-alquilo C1-C6 y -C(O)-O-alquilo C1-C6, y en la que R4, R5 y R18 están opcionalmente sustituidos además con espiro-cicloalquilo C3-C8 o espiro-heterociclilo C3-C8 de tal forma que junto con R4, R5 y/o R18 se forma un espirociclo, donde dicho espiro-heterociclilo C3-C8 comprende opcionalmente uno o más grupos seleccionados entre nitrógeno, -C(O)-, -SO2- y -N(SO2-alquilo C1-C4)- en el anillo, o en la que R4, R5 y R18 están opcionalmente sustituidos además bi-valentemente con uno o más grupos que forman anillos espirocíclicos o reasociados seleccionados entre -alquileno C1-C6, -alquenileno C2-C6 y -alquinileno C4-C6, donde uno o dos centros de carbono pueden reemplazarse opcionalmente por uno o dos heteroátomos seleccionados entre N, O y S y que puede estar opcionalmente sustituido con uno o más grupos en un átomo del anillo o en dos átomos vecinos en el anillo seleccionados entre -OH, -NH2, -alquilo C1-C3, O-alquilo C1-C6, -CN, -CF3, -OCF3 y halógeno; en la que R6 se selecciona entre -H, -alquilo C1-C4, -OH, -O-alquilo C1-C4, -halógeno, -CN, -CF3 y -OCF3; en la que A se selecciona entre un enlace sencillo, -CH2-, -O-, -S- y -NH-; en la que n es 1, 2 ó 3; en la que Z es C o N, así como en forma de sus sales de adición de ácidos con ácidos farmacológicamente aceptables.
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Families Citing this family (51)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2155689B1 (en) * 2007-05-31 2015-07-08 Boehringer Ingelheim International GmbH Ccr2 receptor antagonists and uses thereof
SG10201605472WA (en) 2008-01-04 2016-09-29 Intellikine Llc Certain Chemical Entities, Compositions And Methods
US8193182B2 (en) 2008-01-04 2012-06-05 Intellikine, Inc. Substituted isoquinolin-1(2H)-ones, and methods of use thereof
EP2346508B1 (en) 2008-09-26 2016-08-24 Intellikine, LLC Heterocyclic kinase inhibitors
DK2379525T3 (en) 2008-12-19 2015-10-19 Boehringer Ingelheim Int Cyclic pyrimidin-4-carboxamides, as CCR2 receptor antagonists for the treatment of inflammation, asthma and COPD
CN102378757A (zh) * 2009-03-30 2012-03-14 安斯泰来制药株式会社 嘧啶化合物
EP2427195B1 (en) 2009-05-07 2019-05-01 Intellikine, LLC Heterocyclic compounds and uses thereof
US8338441B2 (en) 2009-05-15 2012-12-25 Gilead Sciences, Inc. Inhibitors of human immunodeficiency virus replication
EP2513086B1 (en) * 2009-12-17 2015-04-29 Boehringer Ingelheim International GmbH Novel antagonists for ccr2 and uses thereof
SI2513093T1 (sl) * 2009-12-17 2014-11-28 Boehringer Ingelheim International Gmbh Novi CCR2 receptorski antagonisti in njihove uporabe
US8946218B2 (en) 2010-05-12 2015-02-03 Boehringer Ingelheim International Gmbh CCR2 receptor antagonists, method for producing the same, and use thereof as medicaments
JP2013526507A (ja) * 2010-05-12 2013-06-24 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規ｃｃｒ２受容体アンタゴニスト、その製造方法及び薬物としてのその使用
WO2011144501A1 (en) 2010-05-17 2011-11-24 Boehringer Ingelheim International Gmbh Ccr2 antagonists and uses thereof
WO2011146882A1 (en) 2010-05-21 2011-11-24 Intellikine, Inc. Chemical compounds, compositions and methods for kinase modulation
JP5636094B2 (ja) 2010-05-25 2014-12-03 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｃｃｒ２受容体アンタゴニスト
EP2576538B1 (en) 2010-06-01 2015-10-28 Boehringer Ingelheim International GmbH New CCR2 antagonists
CN103298474B (zh) 2010-11-10 2016-06-29 无限药品股份有限公司 杂环化合物及其用途
AR084824A1 (es) 2011-01-10 2013-06-26 Intellikine Inc Procesos para preparar isoquinolinonas y formas solidas de isoquinolinonas
EP2721025B1 (en) * 2011-06-16 2015-11-25 Boehringer Ingelheim International Gmbh New selective ccr2 antagonists
EP2731941B1 (en) * 2011-07-15 2019-05-08 Boehringer Ingelheim International GmbH Novel and selective ccr2 antagonists
CA2842190A1 (en) 2011-07-19 2013-01-24 Infinity Pharmaceuticals Inc. Heterocyclic compounds and uses thereof
US8969363B2 (en) 2011-07-19 2015-03-03 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
RU2014111823A (ru) 2011-08-29 2015-10-10 Инфинити Фармасьютикалз, Инк. Гетероциклические соединения и их применения
US20140329809A1 (en) 2011-10-28 2014-11-06 Galderma Research & Development New leukocyte infiltrate markers for rosacea and uses thereof
SG11201402405QA (en) 2011-11-18 2014-09-26 Heptares Therapeutics Ltd Muscarinic m1 receptor agonists
US8940742B2 (en) 2012-04-10 2015-01-27 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
US8828998B2 (en) 2012-06-25 2014-09-09 Infinity Pharmaceuticals, Inc. Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors
WO2014019023A1 (en) * 2012-08-01 2014-02-06 Bionomics Limited α7 NICOTINIC ACETYLCHOLINE RECEPTOR MODULATORS AND USES THEREOF-I
UA110688C2 (uk) 2012-09-21 2016-01-25 Пфайзер Інк. Біциклічні піридинони
JP6483023B2 (ja) 2012-12-06 2019-03-13 エンリヴェックス セラピューティクス リミテッド 治療用アポトーシス細胞調製物、その製造方法及びその使用
CN103102261A (zh) * 2013-02-06 2013-05-15 上海药明康德新药开发有限公司 一种螺[2.5]辛烷-5-羧酸的合成方法
US9481667B2 (en) 2013-03-15 2016-11-01 Infinity Pharmaceuticals, Inc. Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
WO2015051241A1 (en) 2013-10-04 2015-04-09 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
MY175778A (en) 2013-10-04 2020-07-08 Infinity Pharmaceuticals Inc Heterocyclic compounds and uses thereof
JOP20200052A1 (ar) * 2013-12-19 2017-06-16 Bayer Pharma AG بيبريدينيل تتراهيدرو كوينولينات مستبدلة واستخدامها كمعضدات مستقبل أدريني ألفا- 2c
SG11201607705XA (en) 2014-03-19 2016-10-28 Infinity Pharmaceuticals Inc Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders
WO2015160975A2 (en) 2014-04-16 2015-10-22 Infinity Pharmaceuticals, Inc. Combination therapies
WO2016054491A1 (en) 2014-10-03 2016-04-07 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
EP3050574B1 (en) 2015-01-28 2019-10-09 Universite De Bordeaux Use of plerixafor for treating and/or preventing acute exacerbations of chronic obstructive pulmonary disease
PL3317270T3 (pl) 2015-07-02 2020-11-16 Centrexion Therapeutics Corporation Cytrynian (4-((3r,4r)-3-metoksytetrahydropiran-4-yloamino)piperydyn-1-ylo)(5-metylo-6-(((2r,6s)-6-(p-tolilo)tetrahydro-2h-piran-2-ylo)metylamino)pirymidyn-4-ylo)metanonu
JP6980649B2 (ja) 2015-09-14 2021-12-15 インフィニティー ファーマシューティカルズ， インコーポレイテッド イソキノリノン誘導体の固体形態、それを製造する方法、それを含む組成物、及びそれを使用する方法
GB201519194D0 (en) * 2015-10-30 2015-12-16 Heptares Therapeutics Ltd CGRP receptor antagonists
US10759806B2 (en) 2016-03-17 2020-09-01 Infinity Pharmaceuticals, Inc. Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as PI3K kinase inhibitors
UA120571C2 (uk) 2016-03-22 2019-12-26 Мерк Шарп Енд Дохме Корп. Алостеричні модулятори нікотинових ацетилхолінових рецепторів
WO2017214269A1 (en) 2016-06-08 2017-12-14 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
EP3474856B1 (en) 2016-06-24 2022-09-14 Infinity Pharmaceuticals, Inc. Combination therapies
GB201617454D0 (en) 2016-10-14 2016-11-30 Heptares Therapeutics Limited Pharmaceutical compounds
CN108017599B (zh) * 2016-11-04 2020-03-03 上海爱科百发生物医药技术有限公司 [3-(胺甲基)-氧杂环丁烷-3-基]氨基甲酸对甲氧基苄酯对氯苯甲酸盐合成方法
GB201810239D0 (en) 2018-06-22 2018-08-08 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201819960D0 (en) 2018-12-07 2019-01-23 Heptares Therapeutics Ltd Pharmaceutical compounds
WO2022271982A1 (en) * 2021-06-23 2022-12-29 Synaptive Therapeutics, Llc Substituted phenethylamine for treating inflammation and psychological disorders

Family Cites Families (122)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4032526A (en) 1975-10-02 1977-06-28 American Cyanamid Company 1,2-dimethyl-3 or 5-piperazinyl-pyrazolium salts
US4426382A (en) 1980-02-13 1984-01-17 Sankyo Company Limited 4-Amino-6,7-dimethoxy-2-piperazinylquinazoline derivatives, their preparation and use
US4621305A (en) 1984-08-22 1986-11-04 General Motors Corporation Header connector and attachment
DE3517617A1 (de) 1985-05-15 1986-11-20 Lentia GmbH Chem. u. pharm. Erzeugnisse - Industriebedarf, 8000 München Neue pyridaziniumverbindungen, verfahren zu deren herstellung und diese enthaltende fungizide und algizide mittel
DE3931432A1 (de) * 1989-09-21 1991-04-04 Hoechst Ag Pyrimidin-4,6-dicarbonsaeurediamide, verfahren zu deren herstellung sowie verwendung derselben sowie arzneimittel auf basis dieser verbindungen
US5096916A (en) * 1990-05-07 1992-03-17 Aegis Technology, Inc. Treatment of chronic obstructive pulmonary disease (copd) by inhalation of an imidazoline
JPH08502508A (ja) 1992-10-23 1996-03-19 メルク シヤープ エンド ドーム リミテツド ドーパミンレセプターサブタイプリガンド
JP3166376B2 (ja) 1993-02-03 2001-05-14 松下電器産業株式会社 熱利用装置
TW531537B (en) * 1995-12-27 2003-05-11 Janssen Pharmaceutica Nv 1-(1,2-disubstituted piperidinyl)-4-substituted piperidine derivatives
US5629325A (en) 1996-06-06 1997-05-13 Abbott Laboratories 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling chemical synaptic transmission
US6437138B1 (en) 1996-06-06 2002-08-20 Abbott Laboratories 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling chemical synaptic transmission
US6514977B1 (en) 1997-05-22 2003-02-04 G.D. Searle & Company Substituted pyrazoles as p38 kinase inhibitors
US6979686B1 (en) 2001-12-07 2005-12-27 Pharmacia Corporation Substituted pyrazoles as p38 kinase inhibitors
TR200001171T2 (tr) 1997-10-27 2000-10-23 Neurosearch A/S Nikotinik asetilkolin reseptörlerinde kolinerjik ligandlar olarak heteroaril diazasikloalkalinler
WO2000031072A1 (en) 1998-11-20 2000-06-02 G.D. Searle & Co. Process for making 5-substituted pyrazoles using dithietanes
US6248755B1 (en) 1999-04-06 2001-06-19 Merck & Co., Inc. Pyrrolidine modulators of chemokine receptor activity
WO2000066558A1 (en) 1999-05-04 2000-11-09 Schering Corporation Piperazine derivatives useful as ccr5 antagonists
JP2003520042A (ja) 2000-01-24 2003-07-02 アイシス・ファーマシューティカルス・インコーポレーテッド 誘導性一酸化窒素シンターゼ発現のアンチセンスモジュレーション
GB0004153D0 (en) 2000-02-23 2000-04-12 Astrazeneca Uk Ltd Novel use
US20020045613A1 (en) 2000-04-27 2002-04-18 Heinz Pauls 1-aroyl-piperidinyl benzamidines
IL152830A0 (en) 2000-05-22 2003-06-24 Aventis Pharma Inc Arylmethylamine derivatives for use as tryptase inhibitors
HU226830B1 (en) 2000-10-12 2009-11-30 Boehringer Ingelheim Pharma Thiotropium bromide monohydrate, method for producing the same and a pharmaceutical composition containing the same
AR035700A1 (es) 2001-05-08 2004-06-23 Astrazeneca Ab Derivados de arilheteroalquilamina, composicion farmaceutica, usos de estos derivados para la fabricacion de medicamentos, metodos de tratamiento, y proceso para la preparacion de estos derivados
DK1401445T3 (da) 2001-06-22 2006-11-27 Boehringer Ingelheim Pharma Krystallinsk anticholinergikum, fremgangsmåde til fremstilling af dette og anvendelse af dette til fremstilling af et lægemiddel
AU2002363236A1 (en) 2001-10-30 2003-05-12 Millennium Pharmaceuticals, Inc. Compounds, pharmaceutical compositions and methods of use therefor
US6806279B2 (en) 2001-12-17 2004-10-19 Sunesis Pharmaceuticals, Inc. Small-molecule inhibitors of interleukin-2
MXPA04007612A (es) 2002-02-05 2004-11-10 Novo Nordisk As Aril- y heteroarilpiperazinas novedosas.
HUP0200849A2 (hu) 2002-03-06 2004-08-30 Sanofi-Synthelabo N-aminoacetil-2-ciano-pirrolidin-származékok, e vegyületeket tartalmazó gyógyszerkészítmények és eljárás előállításukra
US20030195192A1 (en) 2002-04-05 2003-10-16 Fortuna Haviv Nicotinamides having antiangiogenic activity
KR20040090978A (ko) 2002-03-13 2004-10-27 얀센 파마슈티카 엔.브이. 히스톤 디아세틸라제의 신규한 저해제로서의 설포닐-유도체
US20040014744A1 (en) 2002-04-05 2004-01-22 Fortuna Haviv Substituted pyridines having antiangiogenic activity
WO2003090748A1 (fr) 2002-04-24 2003-11-06 Takeda Pharmaceutical Compay Limited. Utilisation de composes a antagonisme anti-ccr
JP3780291B2 (ja) 2002-04-29 2006-05-31 メルク エンド カムパニー インコーポレーテッド テトラヒドロピラニルシクロペンチルテトラヒドロピリドピリジン系のケモカイン受容体活性調節剤
MXPA04011638A (es) 2002-06-05 2005-03-07 Pharmacia Corp Derivados de pirazol como inhibidores de la quinasa p38.
WO2004024710A1 (en) 2002-09-13 2004-03-25 Glaxo Group Limited Urea compounds active as vanilloid receptor antagonists for the treatment of pain
SE0203304D0 (sv) 2002-11-07 2002-11-07 Astrazeneca Ab Novel Coumpounds
GB0229618D0 (en) 2002-12-19 2003-01-22 Cancer Rec Tech Ltd Pyrazole compounds
US20040147561A1 (en) 2002-12-27 2004-07-29 Wenge Zhong Pyrid-2-one derivatives and methods of use
WO2004074438A2 (en) 2003-02-14 2004-09-02 Smithkline Beecham Corporation Ccr8 antagonists
MXPA05009661A (es) 2003-03-12 2006-03-08 Kudos Pharm Ltd Derivados de ftalazinona.
EP1615909B1 (en) 2003-04-23 2008-07-23 Glaxo Group Limited Piperazine derivatives and their use for the treatment of neurological and psychiatric diseases
FR2854158B1 (fr) 2003-04-25 2006-11-17 Sanofi Synthelabo Derives de 2-acylamino-4-phenylethiazole, leur preparation et leur application en therapeutique
WO2005014571A1 (en) 2003-07-18 2005-02-17 Glaxo Group Limited Substituted piperidines as histamine h3 receptor ligands
DK1651615T3 (da) 2003-07-29 2010-05-25 High Point Pharmaceuticals Llc Pyridazinyl-piperaziner og anvendelse deraf som histamin-H3-receptorligander
ES2439894T3 (es) 2003-12-18 2014-01-27 Incyte Corporation Derivados de 3-cicloalquilaminopirrolidina como moduladores de receptores de quimioquina
GB0403155D0 (en) * 2004-02-12 2004-03-17 Vernalis Res Ltd Chemical compounds
AU2005219438B2 (en) 2004-03-03 2011-02-17 Chemocentryx, Inc. Bicyclic and bridged nitrogen heterocycles
PE20060285A1 (es) 2004-03-30 2006-05-08 Aventis Pharma Inc Piridonas sustituidas como inhibidores de pol(adp-ribosa)-polimerasa (parp)
MXPA06011414A (es) 2004-03-31 2007-04-20 Johnson & Johnson Compuestos heterociclicos sin imidazol como ligandos del receptor de h3 histamina.
AU2005249380C1 (en) 2004-04-23 2012-09-20 Exelixis, Inc. Kinase modulators and methods of use
EP1753740A2 (en) 2004-05-21 2007-02-21 Merck & Co., Inc. Amino cyclopentyl heterocyclic and carbocyclic modulators of chemokine receptor activity
CA2569016C (en) 2004-06-02 2012-11-27 Takeda Pharmaceutical Company Limited Fused heterocyclic compound
FR2871157A1 (fr) 2004-06-04 2005-12-09 Aventis Pharma Sa Produits biaryl aromatiques, compositions les contenant et utilisation
EP1758580A4 (en) 2004-06-24 2008-01-16 Incyte Corp N-SUBSTITUTED PIPERIDINE AND ITS USE AS A MEDICAMENT
NZ552173A (en) 2004-06-25 2010-07-30 Janssen Pharmaceutica Nv Quaternary salt CCR2 antagonists
EP1763347A4 (en) 2004-06-28 2009-05-20 Incyte Corp 3-AMINOCYCLOPENTANECARBOXAMIDES AS MODULATORS OF CHEMOKINE RECEPTORS
GB0419072D0 (en) * 2004-08-26 2004-09-29 Kudos Pharm Ltd Phthalazinone derivatives
NZ553979A (en) * 2004-08-26 2009-05-31 Kudos Pharm Ltd 4-heteroarylmethyl substituted phthalazinone derivatives
GB0420831D0 (en) 2004-09-17 2004-10-20 Glaxo Group Ltd Novel compounds
CA2580855A1 (en) 2004-09-20 2006-03-30 Xenon Pharmaceuticals Inc. Heterocyclic derivatives and their use as stearoyl-coa desaturase inhibitors
GB0421525D0 (en) * 2004-09-28 2004-10-27 Novartis Ag Inhibitors of protein kineses
WO2006038734A1 (en) 2004-10-08 2006-04-13 Astellas Pharma Inc. Pyridazinone derivatives cytokines inhibitors
US8367672B2 (en) 2004-11-02 2013-02-05 Universite De Strasbourg Pyridazine compounds, compositions and methods
UY29219A1 (es) 2004-11-22 2006-04-28 Incyte Corp Sales de la n-(2- (((3r)-1-(trans-4-hidroxi-4-(6-metoxipiridin-3-il)-cilohexil) pirrolidin-3-il)amino)-2-oxoetil)-3- (trifluorometil) benzamida
DE102004061751A1 (de) 2004-12-22 2006-07-06 Bayer Healthcare Ag Cyanoguanidin-substituierte Pyrazoline
TWI385164B (zh) 2005-02-17 2013-02-11 Astellas Pharma Inc Pyridyl non-aromatic nitrogen-containing heterocyclic-1-carboxylate derivatives (II)
EP2527337A1 (en) 2005-04-14 2012-11-28 Bristol-Myers Squibb Company Inhibitors of 11-beta hydroxysteroid dehydrogenase type I
WO2006113140A2 (en) 2005-04-15 2006-10-26 Elan Pharmaceuticals, Inc. Novel compounds useful for bradykinin b1 receptor antagonism
TW200716594A (en) 2005-04-18 2007-05-01 Neurogen Corp Substituted heteroaryl CB1 antagonists
US20080221111A1 (en) 2005-05-11 2008-09-11 Nycomed Gmbh Combination of a Pd4 Inhibitor and a Tetrahydrobiopterin Derivative
CA2609126A1 (en) 2005-05-20 2006-11-30 Vertex Pharmaceuticals Incorporated Pyrrolopyridines useful as inhibitors of protein kinase
AU2006264966B2 (en) 2005-07-04 2013-02-21 High Point Pharmaceuticals, Llc Histamine H3 receptor antagonists
EP1909797A4 (en) 2005-08-02 2013-02-27 Neurogen Corp DIPIPERAZINYL KETONE AND RELATED ANALOG
GB0517184D0 (en) 2005-08-22 2005-09-28 Glaxo Group Ltd Compounds
AR055203A1 (es) * 2005-08-31 2007-08-08 Otsuka Pharma Co Ltd Derivados de benzotiofeno con propiedades antipsicoticas
TW200800999A (en) 2005-09-06 2008-01-01 Astrazeneca Ab Novel compounds
CN101272685A (zh) 2005-09-27 2008-09-24 Irm责任有限公司 包含二芳基胺的化合物和组合物以及它们作为c-kit受体调节剂的用途
JO2769B1 (en) 2005-10-26 2014-03-15 جانسين فارماسوتيكا ان. في Rapid decomposition of physiologically antagonistic agents of the 2-dopamine receptor
US8067457B2 (en) 2005-11-01 2011-11-29 Millennium Pharmaceuticals, Inc. Compounds useful as antagonists of CCR2
US20100016289A1 (en) 2005-11-01 2010-01-21 Kevin Sprott Compounds Useful as Antagonists of CCR2
JP2009515904A (ja) 2005-11-14 2009-04-16 アイアールエム・リミテッド・ライアビリティ・カンパニー Ｌｘｒモジュレーターとしての化合物および組成物
US20090005363A1 (en) * 2005-12-20 2009-01-01 Ralf Glatthar Organic Compounds
WO2007084868A2 (en) 2006-01-17 2007-07-26 Kalypsys, Inc. Treatment of disorders by activation of the unfolded protein response
JO2660B1 (en) 2006-01-20 2012-06-17 نوفارتيس ايه جي Pi-3 inhibitors and methods of use
EP2465850B1 (en) 2006-02-28 2016-11-23 Dart Neuroscience (Cayman) Ltd Therapeutic compounds
WO2007105058A2 (en) 2006-03-16 2007-09-20 Pfizer Products Inc. Pyrazole compounds
EP2013174B1 (en) 2006-04-11 2013-05-08 Merck Sharp & Dohme Corp. Diaryl substituted alkanes
US7807671B2 (en) 2006-04-25 2010-10-05 Bristol-Myers Squibb Company Diketo-piperazine and piperidine derivatives as antiviral agents
WO2007127448A2 (en) 2006-04-28 2007-11-08 Northwestern University Salts of pyridazine compounds
CN101472912A (zh) 2006-06-22 2009-07-01 比奥维特罗姆上市公司 作为mnk激酶抑制剂的吡啶和吡嗪衍生物
GB0617575D0 (en) * 2006-09-06 2006-10-18 Syngenta Ltd Herbicidal compounds and compositions
WO2008060621A2 (en) * 2006-11-17 2008-05-22 Abbott Laboratories Aminopyrrolidines as chemokine receptor antagonists
PL2698062T3 (pl) 2006-12-28 2015-12-31 Abbvie Inc Inhibitory polimerazy poli(adp-rybozy)
JP2010518064A (ja) 2007-02-12 2010-05-27 メルク・シャープ・エンド・ドーム・コーポレイション Ａｄおよび関連状態の治療のためのピペラジン誘導体
JP4785881B2 (ja) 2007-02-27 2011-10-05 大塚製薬株式会社 医薬
FR2915552B1 (fr) 2007-04-27 2009-11-06 Technip France Conduite tubulaire flexible pour le transport d'hydrocarbures gazeux.
EP2155689B1 (en) 2007-05-31 2015-07-08 Boehringer Ingelheim International GmbH Ccr2 receptor antagonists and uses thereof
RU2010103104A (ru) 2007-07-02 2011-08-10 Ф.Хоффманн-Ля Рош Аг (Ch) Производные имидазола в качестве антагонистов рецептора ccr2
US7977358B2 (en) 2007-07-26 2011-07-12 Hoffmann-La Roche Inc. Pyrazol derivatives
EP2042516A1 (en) 2007-09-27 2009-04-01 Protaffin Biotechnologie AG Glycosaminoglycan-antagonising MCP-1 mutants and methods of using same
AU2008289135B2 (en) 2007-08-22 2012-02-23 Irm Llc 2-heteroarylamino-pyrimidine derivatives as kinase inhibitors
BRPI0817935A2 (pt) 2007-10-01 2015-04-07 Hoffmann La Roche Derivados de biarila
CN101820789A (zh) 2007-10-12 2010-09-01 黄钟午 鞋带捆绑工具
US20090131417A1 (en) 2007-11-20 2009-05-21 Letavic Michael A Substituted pyridyl amide compounds as modulators of the histamine h3 receptor
WO2009066084A1 (en) * 2007-11-21 2009-05-28 F. Hoffmann-La Roche Ag 2 -morpholinopyrimidines and their use as pi3 kinase inhibitors
JP5385297B2 (ja) * 2007-11-22 2014-01-08 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規化合物
EP2062889A1 (de) 2007-11-22 2009-05-27 Boehringer Ingelheim Pharma GmbH & Co. KG Verbindungen
KR101357966B1 (ko) 2008-06-18 2014-02-03 에프. 호프만-라 로슈 아게 신규 헤테로아릴 카복스아마이드 유도체
JP5693452B2 (ja) * 2008-08-04 2015-04-01 シーエイチディーアイ ファウンデーション，インコーポレーテッド 特定のキヌレニン−３−モノオキシゲナーゼインヒビター、医薬組成物およびそれらの使用方法
GB0815369D0 (en) * 2008-08-22 2008-10-01 Summit Corp Plc Compounds for treatment of duchenne muscular dystrophy
AU2009289378A1 (en) * 2008-09-02 2010-03-11 Boehringer Ingelheim International Gmbh Novel benzamides, production thereof, and use thereof as medicaments
DK2379525T3 (en) 2008-12-19 2015-10-19 Boehringer Ingelheim Int Cyclic pyrimidin-4-carboxamides, as CCR2 receptor antagonists for the treatment of inflammation, asthma and COPD
WO2010094126A1 (en) 2009-02-23 2010-08-26 Merck Frosst Canada Ltd. Heterocyclic derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase
SI2513093T1 (sl) * 2009-12-17 2014-11-28 Boehringer Ingelheim International Gmbh Novi CCR2 receptorski antagonisti in njihove uporabe
EP2513086B1 (en) * 2009-12-17 2015-04-29 Boehringer Ingelheim International GmbH Novel antagonists for ccr2 and uses thereof
JP2013526507A (ja) 2010-05-12 2013-06-24 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 新規ｃｃｒ２受容体アンタゴニスト、その製造方法及び薬物としてのその使用
US8946218B2 (en) 2010-05-12 2015-02-03 Boehringer Ingelheim International Gmbh CCR2 receptor antagonists, method for producing the same, and use thereof as medicaments
WO2011144501A1 (en) 2010-05-17 2011-11-24 Boehringer Ingelheim International Gmbh Ccr2 antagonists and uses thereof
JP5636094B2 (ja) 2010-05-25 2014-12-03 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング Ｃｃｒ２受容体アンタゴニスト
EP2576538B1 (en) 2010-06-01 2015-10-28 Boehringer Ingelheim International GmbH New CCR2 antagonists
EP2721025B1 (en) * 2011-06-16 2015-11-25 Boehringer Ingelheim International Gmbh New selective ccr2 antagonists
EP2731941B1 (en) * 2011-07-15 2019-05-08 Boehringer Ingelheim International GmbH Novel and selective ccr2 antagonists

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