DK2379525T3 - Cyklisk pyrimidin-4-carboxamider, som CCR2-receptor-antagonister til behandling af inflammation, astma og COPD - Google Patents

Cyklisk pyrimidin-4-carboxamider, som CCR2-receptor-antagonister til behandling af inflammation, astma og COPD Download PDF

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DK2379525T3
DK2379525T3 DK09775212.5T DK09775212T DK2379525T3 DK 2379525 T3 DK2379525 T3 DK 2379525T3 DK 09775212 T DK09775212 T DK 09775212T DK 2379525 T3 DK2379525 T3 DK 2379525T3
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amino
alkyl
mmol
phenyl
alkylene
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Heiner Ebel
Sara Frattini
Riccardo Giovannini
Christoph Hoenke
Thomas Trieselmann
Patrick Tielmann
Stefan Scheuerer
Silke Marie Katrin Hobbie
Frank Buettner
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Boehringer Ingelheim Int
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Claims (14)

1. Forbindelse ifølge formel (I),
hvor Ri er -Li-R7, og, hvor U er en binding eller en gruppe valgt blandt methylen, ethylen og ethe- nylen, og, hvor R7 er en ring valgt blandt cyclopropyl, cyclobutyl, cyclopentyl, cyclohe-xyl, cycloheptyl, pyrrolidinyl, piperidinyl, azepanyl, tetrahydrofuranyl, tetrahydropyranyl, oxepanyl, phenyl, pyridyl, og furanyl, hvor U, hvis forskellig fra en binding, eventuelt er substitueret med én eller flere grupper valgt blandt methyl og ethyl, hvor ringen R7, eventuelt er substitueret med én eller flere grupper valgt blandt -F, -Cl, -methyl, -ethyl, -propyl, -i-propyl, -cyclopropyl, -t-butyl, -CF3, -0-CF3, -CN, -0-methyl, furanyl og phenyl, hvor furanylen og phenylen er eventuelt uafhængig substitueret med én eller flere grupper valgt blandt -Ci-C3-alkyl, halogen, -OCH3, -CF3 og -OCF3, eller, hvor ringen R7 er bivalent substitueret med én eller flere grupper valgt blandt
på to tilstødendeatomer, således at en kondenseret ring dannes, hvor R2 er valgt blandt -H, -halogen, -CN, -0-Ci-C4-alkyl, -Ci-C4-alkyl, -CH=CH2, -C=CH, -CF3, -OCF3, -OCF2H og -OCFH2; hvor R3 er valgt blandt -H, -methyl, -ethyl, -propyl, -i-propyl, -cyclopropyl, -OCH3 og -CN; hvor R4 og R5 er uafhængigt af hinanden valgt blandt et elektronpar, -H, og en gruppe valgt blandt -Ci-C6-alkyl, -NH2, -C3-C8-cycloalkyl, -C3-C8-heterocyclyl, -C5-Ci0-aryl, -C5-C10-heteroaryl og -C(0)-N(R8,R8), med R8 og R8· valgt blandt -H og -Ci-C5-alkyl, og, hvor R4 og R5, hvis forskellige fra et elektronpar eller -H, er eventuelt uafhængigt substitueret med én eller flere grupper valgt blandt -halogen, -OH, -CF3, -CN, -Ci-C5-alkyl, -0-Ci-C5-alkyl, -0-C3-C8-cycloalkyl, -0-C3-C8-heterocyclyl, -O-C5-Ci0-aryl, -0-C5-Cio-heteroaryl, -C0-C5-alkylen-CN, -C0-C4-alkylen-O-Ci-C4-alkyl, -C0-C4-alkylen-O-C3-C8-cycloalkyl, -C0-C4-alkylen-O-C3-C8-heterocyclyl, -C0-C4-alkylen-O-C5-Ci0-aryl, -C0-C4- alkylen-0-C5-Cio-heteroaryl, -C0-C4-alkylen-Q-Co-C4-alkyl-N(R9,R9.), -C0-C4-alkylen-N(Ri0)-Q-Ci-C4-alkyl, -C0-C4-alkylen-N(R10)-Q-C3 C8-cycloalkyl, -C0-C4-alkylen-N(R10)-Q-C3-C8-heterocyclyl, -Co-C4-alkylen-N(R10)-Q-C5-Cio-aryl, -C0-C4-alkylen-N(Rio)-Q-C5-Cio-heteroaryl, -C0-C4-alkylen-Q-N(R11,R11), -Co-C4-alkylen-N(R12)-Q-N(Ri3,Ri3.), -C0-C4- alkylen-Ri4, -C0-C4-alkylen-Q-Ci-C6-alkyl, -Co-C4-alkylen-Q-C3-Cs-cycloalkyl, -C0-C4- alkylen-Q-C3-C8-heterocyclyl, -C0-C4-alkylen-Q-C5-Ci0-aryl, -C0-C4-alkylen-Q-C5-Ci0-heteroaryl, -C0-C4-alkylen-O-Q-N(R15,R15.) og -C0-C4-alkylen-N(R16)-Q-O-(Ri7). hvor Q er valgt blandt -C(O)- og -S02-, hvor Ri2, Rie, er uafhængigt af hinanden valgt blandt -H, -Ci-C6-alkyl og -C3-C6-cycloalkyl, hvor R9, R9-, Rio, Ru, Ru, R13, R13·, Ris, Ris·, er uafhængigt af hinanden valgt blandt -H, -Ci-C6-alkyl og -C3-C6-cydoalkyl, eller, hvor R9 og R9·, Ru og Ru·, Ri3 og Ri3·, Ri5 og Ri5· sammen danner en -C2-C6-alkylengruppe, hvor Ri4 og Ri7 er uafhængigt af hinanden valgt blandt -H, -Ci-C6-alkyl, -C5-C10-aryl, -C5-Ci0-heteroaryl, -C3-C8-cycloalkyl, og -C3-C8-heterocyclyl, hvor -C3-C8-heterocyclylen eventuelt omfatter nitrogen og/eller -S02- i ringen, og, hvor Ri4 og Ri7 eventuelt er substitueret med én eller flere grupper valgt blandt -OH, -OCH3, -CF3, -OCF3, -CN, -halogen, -Ci-C4-alkyl, =0 og -S02-Ci-C4-alkyl, eller, hvor R4 og / eller R5 er uafhængigt en gruppe ifølge strukturen -L2-Ri8, hvor L2 er valgt blandt -NH- og -N(Ci-C4-alkyl)-, hvor Ris er valgt blandt -C5-Ci0-aryl, -C5-Ci0-heteroaryl, -C3-C8-cycloalkyl og -C3-C8-heterocyclyl, hvor Ris eventuelt er substitueret med én eller flere grupper valgt blandt halogen, -CF3, -OCF3, -CN, -OH, -0-Ci-C4-alkyl, -Ci-C6-alkyl, -NH-C(0)-Ci-C6-alkyl, -N(Ci-C4-alkyl)-C(0)-Ci-C5-alkyl, -C(0)-Ci-C6-alkyl, -S(0)2-Ci-C5-alkyl, -NH-S(0)2-Ci-C6-alkyl, -N(Ci-C4-alkyl)-S(0)2-Ci-C6-alkyl, og -C(0)-0-Ci-C5-alkyl, og, hvor R4, R5 og Ris eventuelt er yderligere substitueret med spiro-C3-C8-cycloalkyl eller spiro-C3-C8-heterocyclyl således at der sammen med 1*4, R5 og/eller Ri8 dannes en spirocyclisk fobindelse, hvor spiro-C3-C8-heterocyclylen eventuelt omfatter én eller flere grupper valgt blandt nitrogen, -C(0)-, -S02- og -N(S02-Ci-C4-alkyl)- i ringen, eller, hvor R4, R5 og Ri8 eventuelt er yderligere bivalent substitueret med én eller flere spirocycliske eller kondenserede ring-dannende grupper valgt blandt -Ci-C6-alkylen, - C2-C6-alkenylen og -C4-C5-alkynylen, hvori ét eller to carboncentre eventuelt kan erstattes af ét eller to heteroatomer valgt blandt N, O og S og som eventuelt kan substitueres med én eller flere grupper på et ringatom eller på to tilstødendeatomer valgt blandt -OH, -NH2, -Ci-C3-alkyl, 0-Ci-C6-alkyl, -CN, -CF3, -OCF3 og halogen; hvor R6 er valgt blandt -H, -Ci-C4-alkyl, -OH, -0-Ci-C4-alkyl, -halogen, -CN, -CF3 og -OCF3; hvor A er valgt blandt en enkeltbinding, -CH2-, -O-, -S- og -NH-; hvor n er 1, 2 eller 3; hvor Z er C eller N, såvel som i form af syreadditionssalte deraf med farmakologisk acceptable syrer.
2. Forbindelse ifølge krav 1, hvor Rx er valgt blandt
3. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R2 er valgt blandt -H, -methyl, -ethyl, -propyl, -i-propyl, -cyclopropyl, -butyl, -i-butyl, -t-butyl, - F, -Cl, -Br, -I, -CN, -CH=CH2, -C=CH og -OCH3.
4. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R2 er valgt blandt -H, -methyl, -ethyl, -Br og -OCH3.
5. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R3 er valgt blandt -H og -methyl.
6. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R4 og R5 er uafhængigt valgt blandt et elektron par, -H og en gruppe valgt blandt -i-propyl, -amino, -pyrrolidinyl, -piperidinyl, -morpholinyl, -azepanyl, -oxazepanyl, -piperazinyl, -azetidinyl, -tetrahydropyranyl, -cyclopentyl, -cyclohexyl, og -C(0)-N(R8,R8), med R8 og R8· uafhængigt af hinanden valgt blandt -H og -Ci-C6-alkyl, hvor R4 og R5, hvis forskellige fra et elektronpar og -H eventuelt er uafhængigt substitueret med én eller flere grupper valgt blandt -fluor, -methyl, -ethyl, propyl, -i-propyl, -butyl, -i-butyl, -t-butyl, -hydroxy, -CF3, -OCF3, -CN, -0-CH3, -0-C2Hs, -0-C3H7, -CH2-CN, -CH2-0-CH3, -(CH2)2-0-CH3, -C(0)-CH3, -C(O)-C2H5, -C(0)-C3H7, -COOH, -C(0)-NH2, -C(0)-NH-CH3, -C(0)-N(CH3)2, -NH-C(0)-CH3, -N(CH3)C(0)-CH3, -NH-C(0)-C2H5, -N(CH3)-C(0)-C2H5, -NH-C(0)-C3H7, -N(CH3)-C(0)-C3H7, -NH-S02-CH3, -N(CH3)-S02-CH3, -N(C2H5)-S02-CH3, -N(C3H7)-S02-CH3, -nh-so2-c2h5, -N(CH3)-S02-C2H5, -N(C2H5)-S02-C2H5, -N(C3H7)-S02-C2H5, -NH-S02-C3H7, -N(CH3)-S02- C3H7, -N(C2H5)-S02-C3H7, -N(C3H7)-S02-C3H7, -nh-so2-c3h5, -N(CH3)-S02-C3H5, -N(C2Hs)-S02-C3H5, -N(C3H7)-S02-C2H5, -CH2-NH-S02-CH3, -CH2-N(CH3)-S02-CH3, -ch2-nh-so2-c2h5, -CH2-N(CH3)-S02-C2H5, -ch2-nh-so2-c3h7, -CH2-N(CH3)-S02-C3H7, -ch2-nh-so2-C3H5, -CH2-N(CH3)-S02-C3H5, -NH-C(0)-NH2, -N(CH3)-C(0)-NH2, -NH-C(0)-NH-CH3, -N(CH3)-C(0)-NH-CH3, -NH-C(0)-N(CH3)2, -N(CH3)-C(0)-N(CH3)2, -S02-NH2, -S02-NH(CH3), -S02-N(CH3)2, -C(0)-NH-C2H5, -C(0)-N(CH3)-C2H5, -C(0)-N(CH3)-C3H7, -C(0)-N(CH3)-C4H9, -C(0)-NH-CH(CH3)-C2H5, -C(0)-N(CH3)-CH(CH3)-C2H5, -CH2-C(0)-NH2, -CH2-C(0)-NH-CH3, -CH2-C(0)-N(CH3)2, -N(CH3)-S02-N(CH3)2, -phenyl, -pyridin-4-yl, -CH2-3-methyl-oxetan-3-yl, -0-l,2-difluor-phen-5-yl, -O-pyridin-2-yl, -pyrrolidin-2-on-l-yl, -3,5-dimethyl-[l,2,4]triazol-4-yl, 3-methyl-[l,2,4]oxadiazol-5-yl,
eller, hvor R4 og R5 er uafhængigt en gruppe ifølge strukturen -L2-Ri8, hvor l_2 er valgt blandt -NH-, -N(CH3)- og -N(C2H5)-, og hvor Ri8 er valgt blandt -tetrahydropyranyl, -cyclopropyl, -cyclobutyl, -cyclopentyl, -cyclohexyl, -cycloheptyl, -cyclooctyl, -pyrrolidinyl, -piperidinyl, -piperazinyl, -morpholinyl, -chromanyl, -octahydro-pyrano-pyrrolyl, -octahydro-pyrano-pyridinyl, -octahydro-pyrano-oxazinyl, -oxaspirodecanyl og -tetrahydro-naphthyridinyl, hvor Ris eventuelt er substitueret med én eller flere grupper valgt blandt -F, -CF3, -OCF3, -CN, -OH, -0-CH3, -CH3, -NH-C(0)-CH3, -N(CH3)-C(0)-CH3, -C(0)-CH3, -S(0)2-CH3, -NH-S(0)2-CH3, -N(CH3)-S(0)2-CH3 og -C(0)-0-C2H5, og, hvor R4, R5 og Ri8 eventuelt er yderligere bivalent substituerede med én eller flere grupper valgt blandt
på ét ringatom eller på to tilstødendeatomer, således at spirocykliske eller kondenserede ringe dannes.
7. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R4 er valgt blandt
8. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R5 er valgt blandt et elektronpar, -H og -C(0)-NH2.
9. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R6 er valgt blandt -H, -CH3, -C2H5, -0-CH3, -0-C2H5, -F, -CF3 og -OCF3.
10. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor R5 er Fl eller -0-CF3.
11. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor A er -0-eller -NFI-.
12. Forbindelse ifølge et hvilket som helst af de foregående krav valgt fra gruppen bestående af
13. Forbindelse ifølge et hvilket som helst af de foregående krav til anvendelse som et lægemiddel.
14. Forbindelse ifølge et hvilket som helst af krav 1-12 til anvendelse i behandlingen af slidgigt, diabetisk nefropati, lændesmerte, neuropatisk smerte eller en smertesygdom.
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Families Citing this family (59)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008145681A2 (en) 2007-05-31 2008-12-04 Boehringer Ingelheim International Gmbh Ccr2 receptor antagonists and uses thereof
CA2711558C (en) 2008-01-04 2016-12-13 Intellikine, Inc. Phosphatidyl inositol-3 kinase inhibiting compounds
US8193182B2 (en) 2008-01-04 2012-06-05 Intellikine, Inc. Substituted isoquinolin-1(2H)-ones, and methods of use thereof
JP5731978B2 (ja) 2008-09-26 2015-06-10 インテリカイン， エルエルシー 複素環キナーゼ阻害剤
DK2379525T3 (da) 2008-12-19 2015-10-19 Boehringer Ingelheim Int Cyklisk pyrimidin-4-carboxamider, som CCR2-receptor-antagonister til behandling af inflammation, astma og COPD
RU2011143740A (ru) * 2009-03-30 2013-05-10 Астеллас Фарма Инк. Соединение пиримидина
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
WO2011073154A1 (en) * 2009-12-17 2011-06-23 Boehringer Ingelheim International Gmbh New ccr2 receptor antagonists and uses thereof
WO2011073155A1 (en) * 2009-12-17 2011-06-23 Boehringer Ingelheim International Gmbh Novel antagonists for ccr2 and uses thereof
EP2569295B1 (en) 2010-05-12 2014-11-19 Boehringer Ingelheim International GmbH New ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments
US8877745B2 (en) 2010-05-12 2014-11-04 Boehringer Ingelheim International Gmbh CCR2 receptor antagonists, method for producing the same, and use thereof as medicaments
US8841313B2 (en) 2010-05-17 2014-09-23 Boehringer Ingelheim International Gmbh CCR2 antagonists and uses thereof
AU2011255218B2 (en) 2010-05-21 2015-03-12 Infinity Pharmaceuticals, Inc. Chemical compounds, compositions and methods for kinase modulation
US9018212B2 (en) 2010-05-25 2015-04-28 Boehringer Ingelheim International Gmbh Pyridazine carboxamides as CCR2 receptor antagonists
EP2576538B1 (en) 2010-06-01 2015-10-28 Boehringer Ingelheim International GmbH New CCR2 antagonists
JP2013545749A (ja) 2010-11-10 2013-12-26 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 複素環化合物及びその使用
AU2012205669B2 (en) 2011-01-10 2015-08-20 Infinity Pharmaceuticals Inc. Processes for preparing isoquinolinones and solid forms of isoquinolinones
WO2012171863A1 (en) 2011-06-16 2012-12-20 Boehringer Ingelheim International Gmbh New selective ccr2 antagonists
JP5786258B2 (ja) * 2011-07-15 2015-09-30 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 新規かつ選択的なｃｃｒ２拮抗薬
US9056877B2 (en) 2011-07-19 2015-06-16 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
JP6027610B2 (ja) 2011-07-19 2016-11-16 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 複素環式化合物及びその使用
EP2751093A1 (en) 2011-08-29 2014-07-09 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
EP2771484A1 (en) 2011-10-28 2014-09-03 Galderma Research & Development New leukocyte infiltrate markers for rosacea and uses thereof
CN104039321B (zh) 2011-11-18 2017-02-22 赫普泰雅治疗有限公司 药物化合物
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
RU2015106915A (ru) * 2012-08-01 2016-09-20 Мерк Шарп И Доум Корп. МОДУЛЯТОРЫ α7 НИКОТИНОВОГО АЦЕТИЛХОЛИНОВОГО РЕЦЕПТОРА И ИХ ПРИМЕНЕНИЕ
UA110688C2 (uk) 2012-09-21 2016-01-25 Пфайзер Інк. Біциклічні піридинони
KR102229478B1 (ko) 2012-11-01 2021-03-18 인피니티 파마슈티칼스, 인코포레이티드 Pi3 키나아제 동형단백질 조절인자를 사용하는 암의 치료
US10077426B2 (en) 2012-12-06 2018-09-18 Enlivex Therapeutics Ltd Therapeutic apoptotic cell preparations, method for producing same and uses thereof
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
US9751888B2 (en) 2013-10-04 2017-09-05 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
PE20160685A1 (es) 2013-10-04 2016-07-23 Infinity Pharmaceuticals Inc Compuestos heterociclicos y usos de los mismos
WO2015091414A2 (de) * 2013-12-19 2015-06-25 Bayer Pharma Aktiengesellschaft Substituierte piperidinyl-tetrahydrochinoline
GB201404922D0 (en) 2014-03-19 2014-04-30 Heptares Therapeutics Ltd Pharmaceutical compounds
SG10201808053XA (en) 2014-03-19 2018-10-30 Infinity Pharmaceuticals Inc Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders
US20150320755A1 (en) 2014-04-16 2015-11-12 Infinity Pharmaceuticals, Inc. Combination therapies
US9708348B2 (en) 2014-10-03 2017-07-18 Infinity Pharmaceuticals, Inc. Trisubstituted bicyclic heterocyclic compounds with kinase activities and uses thereof
DK3050574T3 (da) 2015-01-28 2020-01-20 Univ Bordeaux Anvendelse af plerixafor til behandling og/eller forebyggelse af akutte forværringer af kronisk obstruktiv lungesygdom
WO2017004537A1 (en) 2015-07-02 2017-01-05 Centrexion Therapeutics Corporation (4-((3r,4r)-3-methoxytetrahydro-pyran-4-ylamino)piperidin-1-yl)(5-methyl-6-(((2r,6s)-6-(p-tolyl)tetrahydro-2h-pyran-2-yl)methylamino)pyrimidin-4yl)methanone citrate
GB201513743D0 (en) 2015-08-03 2015-09-16 Heptares Therapeutics Ltd Muscarinic agonists
US10160761B2 (en) 2015-09-14 2018-12-25 Infinity Pharmaceuticals, Inc. Solid forms of isoquinolinones, and process of making, composition comprising, and methods of using the same
GB201519194D0 (en) * 2015-10-30 2015-12-16 Heptares Therapeutics Ltd CGRP receptor antagonists
GB201519352D0 (en) 2015-11-02 2015-12-16 Heptares Therapeutics Ltd Pharmaceutical compounds
WO2017161116A1 (en) 2016-03-17 2017-09-21 Infinity Pharmaceuticals, Inc. Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as pi3k kinase inhibitors
GEAP202014908A (en) 2016-03-22 2020-03-10 Merck Sharp & Dohme Allosteric modulators of nicotinic acetylcholine receptors
US10919914B2 (en) 2016-06-08 2021-02-16 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
MX391135B (es) 2016-06-24 2025-03-21 Infinity Pharmaceuticals Inc Terapias de combinacion.
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
GB201819961D0 (en) 2018-12-07 2019-01-23 Heptares Therapeutics Ltd Pharmaceutical compounds
GB201819960D0 (en) 2018-12-07 2019-01-23 Heptares Therapeutics Ltd Pharmaceutical compounds
GB202020191D0 (en) 2020-12-18 2021-02-03 Heptares Therapeutics Ltd Pharmaceutical compounds
CN114349728A (zh) * 2020-10-12 2022-04-15 南京药石科技股份有限公司 （3r，4r）-4-氨基四氢吡喃-3-醇及其盐的制备方法
WO2022271982A1 (en) * 2021-06-23 2022-12-29 Synaptive Therapeutics, Llc Substituted phenethylamine for treating inflammation and psychological disorders
EP4725942A1 (en) * 2024-10-09 2026-04-15 Sibylla Biotech S.p.A. Compounds active on cyclin d1 pathway and their use

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
GB2068961B (en) 1980-02-13 1983-11-30 Sankyo Co Quinazoline derivatives
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
US6437138B1 (en) 1996-06-06 2002-08-20 Abbott Laboratories 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling chemical synaptic transmission
US5629325A (en) 1996-06-06 1997-05-13 Abbott Laboratories 3-pyridyloxymethyl heterocyclic ether compounds useful in controlling chemical synaptic transmission
US6979686B1 (en) 2001-12-07 2005-12-27 Pharmacia Corporation Substituted pyrazoles as p38 kinase inhibitors
US6514977B1 (en) 1997-05-22 2003-02-04 G.D. Searle & Company Substituted pyrazoles as p38 kinase inhibitors
AU744539B2 (en) 1997-10-27 2002-02-28 Neurosearch A/S Heteroaryl diazacycloalkanes as cholinergic ligands at nicotinic acetylcholine receptors
CA2350081A1 (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
TR200103214T2 (tr) 1999-05-04 2002-03-21 Schering Corporation CCR5 antagonistleri olarak yararlì piperazin trevleri.
AU2001229501A1 (en) 2000-01-24 2001-07-31 Isis Pharmaceuticals, Inc. Antisense modulation of inducible nitric oxide synthase expression
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
OA12274A (en) 2000-05-22 2006-05-09 Aventis Pharma Inc Arylmethylamine derivatives for use as tryptase inhibitors.
DE50103666D1 (de) 2000-10-12 2004-10-21 Boehringer Ingelheim Pharma Kristallines monohydrat von tiotropiumbromid, verfahren zu dessen herstellung und dessen verwendung zur herstellung eines arzneimittels
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
PL208137B1 (pl) 2001-06-22 2011-03-31 Boehringer Ingelheim Pharma Bezwodny krystaliczny bromek tiotropium, sposób jego wytwarzania i zastosowanie krystalicznego monohydratu bromku tiotropium do wytwarzania krystalicznego bezwodnego bromku tiotropium
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
AU2003203148A1 (en) 2002-02-05 2003-09-02 High Point Pharmaceuticals, Llc Novel aryl- and heteroarylpiperazines
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
ATE395343T1 (de) 2002-03-13 2008-05-15 Janssen Pharmaceutica Nv Sulfonylderivate als histone-deacetylase- inhibitoren
US20040014744A1 (en) 2002-04-05 2004-01-22 Fortuna Haviv Substituted pyridines having antiangiogenic activity
CA2483253A1 (en) 2002-04-24 2003-11-06 Takeda Pharmaceutical Company Limited Use of compounds having ccr antagonism
CA2483752C (en) 2002-04-29 2011-03-29 Merck & Co., Inc. Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity
WO2003104223A1 (en) 2002-06-05 2003-12-18 Pharmacia Corporation Pyrazole-derivatives as p38 kinase inhibitors
AU2003270199A1 (en) 2002-09-13 2004-04-30 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
AU2004220321B2 (en) 2003-03-12 2010-02-25 Kudos Pharmaceuticals Ltd Phthalazinone derivatives
MXPA05011352A (es) 2003-04-23 2005-11-28 Glaxo Group Ltd Derivados de piperazina y su uso para el tratamiento de enfermedades neurologicas y psiquiatricas.
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
CA2532236C (en) 2003-07-29 2011-08-23 Novo Nordisk A/S Pyridazinyl- piperazines and their use as histamine h3 receptor ligands
BRPI0417605B8 (pt) 2003-12-18 2021-05-25 Incyte Corp “n-[2-((3s)-3-{[4-hidróxi-4-(5-pirimidin-2- ilpiridin-2-il)ciclohexil]amino}-pirrolidin-1-il)-2- oxoetil]-3-(trifluor-metil)benzamida, ou um sal farmaceuticamente aceitável do mesmo e composição que o compreende”.
GB0403155D0 (en) * 2004-02-12 2004-03-17 Vernalis Res Ltd Chemical compounds
CN1950082B (zh) 2004-03-03 2013-02-06 凯莫森特里克斯股份有限公司 双环和桥连的含氮杂环化物
PE20060285A1 (es) 2004-03-30 2006-05-08 Aventis Pharma Inc Piridonas sustituidas como inhibidores de pol(adp-ribosa)-polimerasa (parp)
CN1972914A (zh) 2004-03-31 2007-05-30 詹森药业有限公司 作为组胺h3受体配合体的非咪唑杂环化合物
WO2005117909A2 (en) 2004-04-23 2005-12-15 Exelixis, Inc. Kinase modulators and methods of use
US20100234409A1 (en) 2004-05-21 2010-09-16 Lihu Yang Amino cyclopentyl heterocyclic and carbocyclic modulators of chemokine receptor activity
WO2005118588A1 (ja) 2004-06-02 2005-12-15 Takeda Pharmaceutical Company Limited 縮合複素環化合物
FR2871157A1 (fr) 2004-06-04 2005-12-09 Aventis Pharma Sa Produits biaryl aromatiques, compositions les contenant et utilisation
EA200700117A1 (ru) 2004-06-24 2007-06-29 Инсайт Корпорейшн N-замещенные пиперидины и их применение в качестве фармацевтических препаратов
AU2005267385B2 (en) 2004-06-25 2011-11-10 Janssen Pharmaceutica N.V. Quaternary salt CCR2 antagonists
EP1763347A4 (en) 2004-06-28 2009-05-20 Incyte Corp 3-AMINOCYCLOPENTANECARBOXAMIDES AS MODULATORS OF CHEMOKINE RECEPTORS
EP1791827A1 (en) * 2004-08-26 2007-06-06 Kudos Pharmaceuticals Limited 4-heteroarylmethyl substituted phthalazinone derivatives
GB0419072D0 (en) * 2004-08-26 2004-09-29 Kudos Pharm Ltd Phthalazinone derivatives
GB0420831D0 (en) 2004-09-17 2004-10-20 Glaxo Group Ltd Novel compounds
JP4958786B2 (ja) 2004-09-20 2012-06-20 ゼノン・ファーマシューティカルズ・インコーポレイテッド 複素環誘導体および治療薬としてのそれらの使用
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
EP1812408B1 (en) 2004-11-02 2013-10-09 Northwestern University Pyridazine compounds, compositions and methods
PA8653301A1 (es) 2004-11-22 2006-11-09 Incyte Corp Incyte Corp Sales de la n-[2-({(3r)-1-[trans-4-hidroxi-4-(6-metoxipiridin-3-il) ciclohexil)pirrolidin
DE102004061751A1 (de) 2004-12-22 2006-07-06 Bayer Healthcare Ag Cyanoguanidin-substituierte Pyrazoline
MX2007010076A (es) 2005-02-17 2007-10-16 Astellas Pharma Inc Derivado de heterociclico-1-carboxilato que contiene nitrogeno no aromatico de piridilo.
EP2527337A1 (en) 2005-04-14 2012-11-28 Bristol-Myers Squibb Company Inhibitors of 11-beta hydroxysteroid dehydrogenase type I
JP2008537953A (ja) 2005-04-15 2008-10-02 エラン ファーマシューティカルズ，インコーポレイテッド ブラジキニンｂ１受容体拮抗作用に有用な新規化合物
AR053712A1 (es) 2005-04-18 2007-05-16 Neurogen Corp Heteroarilos sustituidos, antagonistas de cb1 (receptor 1 canabinoide)
EP1940392A2 (en) 2005-05-11 2008-07-09 Nycomed GmbH Combination of the pde4 inhibitor and a tetrahydrobiopterin derivative
KR20080016659A (ko) 2005-05-20 2008-02-21 버텍스 파마슈티칼스 인코포레이티드 단백질 키나제의 억제제로서 유용한 피롤로피리딘
EP2386554A1 (en) 2005-07-04 2011-11-16 High Point Pharmaceuticals, LLC Compounds active at the histamine H3 receptor
AU2006275568A1 (en) 2005-08-02 2007-02-08 Neurogen Corporation Dipiperazinyl ketones and related analogues
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
JP5335426B2 (ja) 2005-09-27 2013-11-06 アイアールエム・リミテッド・ライアビリティ・カンパニー ジアリールアミン含有化合物および組成物、ならびにｃ−ｋｉｔ受容体のモジュレーターとしてのそれらの使用
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
WO2007053495A2 (en) 2005-11-01 2007-05-10 Millennium Pharmaceuticals, Inc. Compounds useful as antagonists of ccr2
WO2007092065A2 (en) 2005-11-14 2007-08-16 Irm Llc Compounds and compositions as lxr modulators
AR058554A1 (es) * 2005-12-20 2008-02-13 Novartis Ag Compuestos heterociclicos nitrogenados de 6 miembros sustituidos, metodos para su preparacion, composiciones farmaceuticas que los contienen y su uso en el tratamiento de enfermedades mediadas por mglur5.
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
JP5503874B2 (ja) 2006-02-28 2014-05-28 ダート ニューロサイエンス （ケイマン） エルティーディー 治療化合物
CA2643066A1 (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
US20080039450A1 (en) 2006-06-22 2008-02-14 Jensen Annika J Compounds
GB0617575D0 (en) * 2006-09-06 2006-10-18 Syngenta Ltd Herbicidal compounds and compositions
CN101534824A (zh) * 2006-11-17 2009-09-16 艾博特公司 作为化学活素受体拮抗剂的氨基吡咯烷
PT2698062E (pt) 2006-12-28 2015-10-19 Abbvie Inc Inibidores da poli (adp-ribose) polimerase
EP2121633A2 (en) 2007-02-12 2009-11-25 Merck & Co., Inc. Piperazine derivatives for treatment of ad and related conditions
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.
WO2008145681A2 (en) 2007-05-31 2008-12-04 Boehringer Ingelheim International Gmbh Ccr2 receptor antagonists and uses thereof
CA2691662A1 (en) 2007-07-02 2009-01-08 F. Hoffmann-La Roche Ag Imidazole derivatives as ccr2 receptor antagonists
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
WO2009026204A1 (en) 2007-08-22 2009-02-26 Irm Llc 2-heteroarylamino-pyrimidine derivatives as kinase inhibitors
MX2010003621A (es) 2007-10-01 2010-04-14 Hoffmann La Roche N-heterociclil biaril carboxamidas como antagonistas del receptor ccr.
US20100218349A1 (en) 2007-10-12 2010-09-02 Whang Jong O Tying tool for shoelace
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
EP2062889A1 (de) 2007-11-22 2009-05-27 Boehringer Ingelheim Pharma GmbH & Co. KG Verbindungen
CA2705405A1 (en) 2007-11-22 2009-05-28 Boehringer Ingelheim International Gmbh New compounds
AU2009259496A1 (en) 2008-06-18 2009-12-23 F. Hoffmann-La Roche Ag Novel heteroaryl carboxamide derivatives
NZ601483A (en) * 2008-08-04 2013-10-25 Chdi Foundation Inc Certain kynurenine-3-monooxygenase inhibitors, pharmaceutical compositions, and methods of use thereof
GB0815369D0 (en) * 2008-08-22 2008-10-01 Summit Corp Plc Compounds for treatment of duchenne muscular dystrophy
EP2331506B1 (de) * 2008-09-02 2013-07-03 Boehringer Ingelheim International GmbH Neue benzamide, deren herstellung und deren verwendung als arzneimittel
DK2379525T3 (da) 2008-12-19 2015-10-19 Boehringer Ingelheim Int Cyklisk pyrimidin-4-carboxamider, som CCR2-receptor-antagonister til behandling af inflammation, astma og COPD
JP2012518603A (ja) 2009-02-23 2012-08-16 メルク カナダ インコーポレイテッド ステアロイル−コエンザイムａデルタ−９デサチュラーゼの阻害剤としての複素環誘導体
WO2011073155A1 (en) 2009-12-17 2011-06-23 Boehringer Ingelheim International Gmbh Novel antagonists for ccr2 and uses thereof
WO2011073154A1 (en) * 2009-12-17 2011-06-23 Boehringer Ingelheim International Gmbh New ccr2 receptor antagonists and uses thereof
EP2569295B1 (en) 2010-05-12 2014-11-19 Boehringer Ingelheim International GmbH New ccr2 receptor antagonists, method for producing the same, and use thereof as medicaments
US8877745B2 (en) 2010-05-12 2014-11-04 Boehringer Ingelheim International Gmbh CCR2 receptor antagonists, method for producing the same, and use thereof as medicaments
US8841313B2 (en) 2010-05-17 2014-09-23 Boehringer Ingelheim International Gmbh CCR2 antagonists and uses thereof
US9018212B2 (en) 2010-05-25 2015-04-28 Boehringer Ingelheim International Gmbh Pyridazine carboxamides as CCR2 receptor antagonists
EP2576538B1 (en) 2010-06-01 2015-10-28 Boehringer Ingelheim International GmbH New CCR2 antagonists
WO2012171863A1 (en) 2011-06-16 2012-12-20 Boehringer Ingelheim International Gmbh New selective ccr2 antagonists
JP5786258B2 (ja) * 2011-07-15 2015-09-30 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 新規かつ選択的なｃｃｒ２拮抗薬

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