AR050184A1 - Inhibidores macrociclicos de beta-secretasa - Google Patents
Inhibidores macrociclicos de beta-secretasaInfo
- Publication number
- AR050184A1 AR050184A1 ARP050103099A ARP050103099A AR050184A1 AR 050184 A1 AR050184 A1 AR 050184A1 AR P050103099 A ARP050103099 A AR P050103099A AR P050103099 A ARP050103099 A AR P050103099A AR 050184 A1 AR050184 A1 AR 050184A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- cycloalkyl
- aryl
- heterocyclyl
- aralkyl
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
La presente trata de inhibidores macrocíclicos de beta-secretasa. Además se revelan composiciones farmacéuticas que comprenden los compuestos de formula (1). Se describen también métodos para el tratamiento de enfermedades cognitiva o neurodegenerativas, tales como la enfermedad de Alzheimer. Adicionalmente, se describen métodos para el tratamiento de una enfermedad cognitiva o neurodegenerativa, que comprenden la administracion de una combinacion de por lo menos un compuesto de la formula (1) y por lo menos un compuesto seleccionado del grupo que consiste en inhibidores de beta-secretasa diferentes de los de formula (1); inhibidores de HMG-CoA reductasa; inhibidores de gamma-secretasa; agentes antiinflamatorios no corticoesteroides, antagonistas del receptor de N-metil-D-aspartato; inhibidores de colinesterasa; y anticuerpos antiamiloideos; a un paciente que necesita dicho tratamiento. Reivindicacion 1: Un compuesto que tiene la formula estructural (1) o una sal farmacéuticamente aceptable de dicho compuesto, donde R1 es como se muestra en los restos de formulas (2) o (3); R2 es -N(R5)C(O)R4- o un anillo heterociclileno; R3 es arileno, heteroarileno, heterociclileno o cicloalquileno; R4 es arileno, heteroarileno, heterociclileno o cicloalquileno; R5 es H, alquilo, arilo, heteroarilo o cicloalquilo; R6 y R7 se seleccionan de manera independiente de H, -OH, alquilo, cicloalquilo, cicloalquilalquilo, heterociclilo, arilo, heteroarilo, aralquilo, heteroaralquilo, aralcoxi, heteroaralcoxi y alcoxi, con la condicion de que cuando R6 y R7 son -OH, aralcoxi, heteroaralcoxi y alcoxi, R6 y R7 no están unidos a un C de anillo adyacente a un N de anillo; R8 es H, alquilo, cicloalquilo, cicloalquilalquilo, arilo, heteroarilo, aralquilo, heteroaralquilo, heterociclilo, heterociclilalquilo, -C(O)R9, -C(O)OR12, , -S(O)R9, -S(O2)R9 o -CN; con la condicion de que cuando Y es =O, R8 no puede ser -C(O)R9, -C(O)OR12, -S(O)R9, --S(O2)R9 o - CN; R9 es H, alquilo, cicloalquilo, arilo, heteroarilo, cicloalquilalquilo, aralquilo, heteroaralquilo, heterociclilo, heterociclilalquilo, alquenilo, alquinilo o -N(R10)(R11); R10 y R11 se seleccionan de manera independiente del grupo que consiste en h, alquilo, cicloalquilo, cicloalquilalquilo, arilo, heteroarilo, heterociclilo, aralquilo, heteroaralquilo, heterociclilalquilo, alquenilo y alquinilo; o R10 y R11 junto con el N al que están unidos forman un anillo heterociclilo de 3 a 7 miembros; R12 es alquilo, cicloalquilo, arilo, heteroarilo, cicloalquilalquilo, aralquilo, heteroaralquilo, heterociclilo, heterociclilalquilo, alquenilo o alquinilo; X es O, S, C(R5), o NH; Y es =O, o (H,H); m es 1, 2 o 3; n es 0, 1, 2, o 3 y o es 0, 1, 2 o 3; donde cada alquilo está opcionalmente sustituido con 1 a 3 porciones seleccionadas del grupo que consiste en halo, arilo, cicloalquilo, ciano, hidroxi, alcoxi, alquiltio, amino, -NH(alquilo), -NH(cicloalquilo), -N(alquilo)2, carboxi y - C(O)O-alquilo; y donde cada arileno, heteroarileno, heterociclilo, heterociclilalquilo, heterociclileno, cicloalquileno, cicloalquilo, cicloalquilalquilo, arilo, heteroarilo, heterociclilo, aralquilo, heteroaralquilo, aralcoxi o heteroaralcoxi está opcionalmente sustituido con 1 a 4 porciones seleccionadas del grupo que consiste en -CF3, alquilo, alquenilo, alquinilo, arilo, heteroarilo, aralquilo, alquilarilo, heteroaralquilo, heteroarilalquenilo, heteroarilalquinilo, alquilheteroarilo, hidroxi, hidroxialquilo, alcoxi, ariloxi, aralcoxi, acilo, aroílo, halo, nitro, ciano, carboxi, alcoxicarbonilo, ariloxicarbonilo, aralcoxicarbonilo, alquilsulfonilo, arilsulfonilo, heteroarilsulfonilo, alquiltio, ariltio, heteroariltio, aralquiltio, heteroaralquiltio, cicloalquilo, heterociclilo, -C(=N-CN)-NH2, -C(=NH)-NH2, -C(=NH)-NH(alquilo), Y1Y2N-, Y1Y2N-alquilo-, Y1Y2NC(O)-, Y1Y2NSO2- y -SO2NY1Y2, en donde Y1 e Y2 pueden ser iguales o diferentes, y se seleccionan de manera independiente del grupo que consiste en H, alquilo, arilo, cicloalquilo, y aralquilo, con la condicion de que cicloalquileno y heterociclileno pueden estar sustituidos con =O.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US59189904P | 2004-07-28 | 2004-07-28 |
Publications (1)
Publication Number | Publication Date |
---|---|
AR050184A1 true AR050184A1 (es) | 2006-10-04 |
Family
ID=35106859
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP050103099A AR050184A1 (es) | 2004-07-28 | 2005-07-26 | Inhibidores macrociclicos de beta-secretasa |
Country Status (13)
Country | Link |
---|---|
US (2) | US7652003B2 (es) |
EP (1) | EP1781644B1 (es) |
JP (1) | JP2008508289A (es) |
CN (1) | CN101027297B (es) |
AR (1) | AR050184A1 (es) |
AT (1) | ATE396990T1 (es) |
CA (1) | CA2575340A1 (es) |
DE (1) | DE602005007245D1 (es) |
ES (1) | ES2306200T3 (es) |
HK (1) | HK1102328A1 (es) |
MX (1) | MX2007001102A (es) |
TW (1) | TWI297337B (es) |
WO (1) | WO2006014944A1 (es) |
Families Citing this family (50)
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DE10303974A1 (de) | 2003-01-31 | 2004-08-05 | Abbott Gmbh & Co. Kg | Amyloid-β(1-42)-Oligomere, Verfahren zu deren Herstellung und deren Verwendung |
US7700603B2 (en) | 2003-12-15 | 2010-04-20 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
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US7592348B2 (en) | 2003-12-15 | 2009-09-22 | Schering Corporation | Heterocyclic aspartyl protease inhibitors |
GB0500683D0 (en) | 2005-01-13 | 2005-02-23 | Novartis Ag | Organic compounds |
EP1851208A1 (en) * | 2005-01-13 | 2007-11-07 | Novartis AG | Macrocyclic compounds useful as bace inhibitors |
ES2350854T3 (es) * | 2005-06-14 | 2011-01-27 | Schering Corporation | Inhibidores de aspartil proteasa. |
SG162790A1 (en) | 2005-06-14 | 2010-07-29 | Schering Corp | Aspartyl protease inhibitors |
PL1954718T3 (pl) | 2005-11-30 | 2015-04-30 | Abbvie Inc | Przeciwciała skierowane przeciwko A globulomerowi, ich reszty wiążące antygeny, odpowiednie hybrydomy, kwasy nukleinowe, wektory, komórki gospodarze, sposoby wytwarzania tych przeciwciał, kompozycje zawierające te przeciwciała, zastosowania tych przeciwciał i sposoby stosowania tych przeciwciał |
JP5486808B2 (ja) | 2005-11-30 | 2014-05-07 | アッヴィ・インコーポレイテッド | アミロイドベータタンパク質に対するモノクローナル抗体及びその使用 |
CN101484429A (zh) | 2006-06-12 | 2009-07-15 | 先灵公司 | 杂环的天冬氨酰基蛋白酶抑制剂 |
CN101484431A (zh) * | 2006-07-20 | 2009-07-15 | 诺瓦提斯公司 | 大环内酰胺 |
JP2010505833A (ja) | 2006-10-06 | 2010-02-25 | メルク エンド カムパニー インコーポレーテッド | アルツハイマー病を治療するためのマクロ環式スピロピペリジンβ−セクレターゼ阻害剤 |
WO2008055945A1 (en) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
US8455626B2 (en) | 2006-11-30 | 2013-06-04 | Abbott Laboratories | Aβ conformer selective anti-aβ globulomer monoclonal antibodies |
US9126987B2 (en) | 2006-11-30 | 2015-09-08 | Probiodrug Ag | Inhibitors of glutaminyl cyclase |
KR20090087487A (ko) | 2006-12-12 | 2009-08-17 | 쉐링 코포레이션 | 아스파르틸 프로테아제 억제제 |
US20100311767A1 (en) | 2007-02-27 | 2010-12-09 | Abbott Gmbh & Co. Kg | Method for the treatment of amyloidoses |
CA2679446C (en) | 2007-03-01 | 2016-05-17 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
DK2142514T3 (da) | 2007-04-18 | 2015-03-23 | Probiodrug Ag | Thioureaderivater som glutaminylcyclase-inhibitorer |
WO2009032277A1 (en) | 2007-09-06 | 2009-03-12 | Schering Corporation | Gamma secretase modulators |
WO2009061699A1 (en) | 2007-11-05 | 2009-05-14 | Schering Corporation | Gamma secretase modulators |
CN101945868A (zh) * | 2007-12-11 | 2011-01-12 | 先灵公司 | γ分泌酶调节剂 |
CA2723222C (en) | 2008-04-22 | 2013-04-02 | Schering Corporation | Phenyl-substituted 2-imino-3-methyl pyrrolo pyrimidinone compounds as bace-1 inhibitors, compositions, and their use |
MX2011005046A (es) | 2008-11-13 | 2011-06-01 | Schering Corp | Moduladores de gamma secretasa. |
JP2012513399A (ja) | 2008-12-22 | 2012-06-14 | シェーリング コーポレイション | γ−セクレターゼ調節剤 |
WO2010075204A2 (en) | 2008-12-22 | 2010-07-01 | Schering Corporation | Gamma secretase modulators |
US20120238546A1 (en) | 2009-06-16 | 2012-09-20 | Zhaoning Zhu | Gamma secretase modulators |
WO2010147975A1 (en) | 2009-06-16 | 2010-12-23 | Schering Corporation | Gamma secretase modulators |
US20120232108A1 (en) | 2009-06-16 | 2012-09-13 | Xianhai Huang | Gamma secretase modulators |
WO2011029920A1 (en) | 2009-09-11 | 2011-03-17 | Probiodrug Ag | Heterocylcic derivatives as inhibitors of glutaminyl cyclase |
UA108363C2 (uk) | 2009-10-08 | 2015-04-27 | Похідні імінотіадіазиндіоксиду як інгібітори bace, композиція на їх основі і їх застосування | |
EP2485590B1 (en) | 2009-10-08 | 2015-01-07 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
EP2485920B1 (en) | 2009-10-08 | 2016-04-27 | Merck Sharp & Dohme Corp. | Pentafluorosulfur imino heterocyclic compounds as bace-1 inhibitors, compositions, and their use |
WO2011044187A1 (en) | 2009-10-08 | 2011-04-14 | Schering Corporation | Iminothiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
JP6026284B2 (ja) | 2010-03-03 | 2016-11-16 | プロビオドルグ エージー | グルタミニルシクラーゼの阻害剤 |
BR112012022478B1 (pt) | 2010-03-10 | 2021-09-21 | Probiodrug Ag | Inibidores heterocíclicos de glutaminil ciclase (qc, ec 2.3.2.5), seu processo de preparação, e composição farmacêutica |
CN104744591B (zh) | 2010-04-15 | 2022-09-27 | Abbvie德国有限责任两合公司 | β淀粉样蛋白结合蛋白 |
EP2560953B1 (en) | 2010-04-21 | 2016-01-06 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
CN105348387B (zh) | 2010-08-14 | 2020-08-25 | Abbvie 公司 | β淀粉样蛋白结合蛋白 |
EP2686313B1 (en) | 2011-03-16 | 2016-02-03 | Probiodrug AG | Benzimidazole derivatives as inhibitors of glutaminyl cyclase |
US9221839B2 (en) | 2011-04-07 | 2015-12-29 | Merck Sharp & Dohme Corp. | C5-C6 oxacyclic-fused thiadiazine dioxide compounds as BACE inhibitors, compositions, and their use |
EP2747769B1 (en) | 2011-08-22 | 2017-08-02 | Merck Sharp & Dohme Corp. | 2-spiro-substituted iminothiazines and their mono-and dioxides as bace inhibitors, compositions and their use |
AU2013235422B2 (en) | 2012-03-19 | 2016-12-15 | Buck Institute For Research On Aging | APP specific BACE inhibitors (ASBIs) and uses thereof |
WO2014056816A1 (en) | 2012-10-10 | 2014-04-17 | F. Hoffmann-La Roche Ag | COMBINATION OF AN Aβ ANTIBODY AND A BACE INHIBITOR |
WO2014062549A1 (en) | 2012-10-17 | 2014-04-24 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as bace inhibitors, compositions, and their use |
US9416129B2 (en) | 2012-10-17 | 2016-08-16 | Merck Sharp & Dohme Corp. | Tricyclic substituted thiadiazine dioxide compounds as BACE inhibitors, compositions and their use |
US10202355B2 (en) | 2013-02-12 | 2019-02-12 | Buck Institute For Research On Aging | Hydantoins that modulate bace-mediated app processing |
CN105175488A (zh) * | 2015-09-07 | 2015-12-23 | 西北农林科技大学 | 一种具有抗老年痴呆症活性的化合物及其制备方法 |
EP3461819B1 (en) | 2017-09-29 | 2020-05-27 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
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EP0395664A1 (en) | 1987-10-21 | 1990-11-07 | The Upjohn Company | Renin inhibitors containing a (1-amino-2-hydroxy-2-heterocyclic) ethyl moiety |
PE20020276A1 (es) | 2000-06-30 | 2002-04-06 | Elan Pharm Inc | COMPUESTOS DE AMINA SUSTITUIDA COMO INHIBIDORES DE ß-SECRETASA PARA EL TRATAMIENTO DE ALZHEIMER |
AU2001273113A1 (en) | 2000-06-30 | 2002-01-14 | Elan Pharmaceuticals, Inc | Compounds to treat alzheimer's disease |
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BR0210391A (pt) * | 2001-06-12 | 2004-06-15 | Elan Pharm Inc | Composto, métodos de tratar um paciente que tenha ou de prevenir um paciente de contrair uma doença ou condição e de preparar um composto, e, uso de um composto |
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US20040171614A1 (en) * | 2002-02-06 | 2004-09-02 | Schering-Plough Corporation | Novel gamma secretase inhibitors |
CA2505098A1 (en) * | 2002-11-12 | 2004-05-27 | Merck & Co., Inc. | Phenylcarboxamide beta-secretase inhibitors for the treatment of alzheimer's disease |
EP1583750B1 (en) * | 2003-01-07 | 2013-02-27 | Merck Sharp & Dohme Corp. | Macrocyclic beta-secretase inhibitors for treatment of Alzheimer's disease |
TW200602045A (en) | 2004-06-16 | 2006-01-16 | Wyeth Corp | Amino-5, 5-diphenylimidazolone derivatives for the inhibition of β-secretase |
AU2005264917A1 (en) * | 2004-06-16 | 2006-01-26 | Wyeth | Diphenylimidazopyrimidine and -imidazole amines as inhibitors of B-secretase |
TW200738683A (en) | 2005-06-30 | 2007-10-16 | Wyeth Corp | Amino-5-(5-membered)heteroarylimidazolone compounds and the use thereof for β-secretase modulation |
CN101213183A (zh) | 2005-06-30 | 2008-07-02 | 惠氏公司 | 氨基-5-(6元)杂芳基咪唑酮化合物和在β-分泌酶调节中的用途 |
TW200730523A (en) | 2005-07-29 | 2007-08-16 | Wyeth Corp | Cycloalkyl amino-hydantoin compounds and use thereof for β-secretase modulation |
KR20080050430A (ko) * | 2005-09-26 | 2008-06-05 | 와이어쓰 | 베타-세크레타제 (bace) 억제제로서아미노-5-[4-(디플루오로메톡시)페닐]-5-페닐이미다졸론화합물 |
JP2009532464A (ja) | 2006-04-05 | 2009-09-10 | アストラゼネカ・アクチエボラーグ | 2−アミノピリミジン−4−オン及びAβ−関連の病理を治療又は予防するためのその使用 |
TW200808796A (en) | 2006-06-14 | 2008-02-16 | Astrazeneca Ab | New compounds III |
TW200815447A (en) | 2006-06-14 | 2008-04-01 | Astrazeneca Ab | Novel compounds IV |
TW200815449A (en) | 2006-06-14 | 2008-04-01 | Astrazeneca Ab | Novel compounds II |
TW200815443A (en) | 2006-06-14 | 2008-04-01 | Astrazeneca Ab | Novel compounds I |
TW200815349A (en) | 2006-06-22 | 2008-04-01 | Astrazeneca Ab | New compounds |
-
2005
- 2005-07-26 MX MX2007001102A patent/MX2007001102A/es active IP Right Grant
- 2005-07-26 US US11/189,346 patent/US7652003B2/en active Active
- 2005-07-26 CA CA002575340A patent/CA2575340A1/en not_active Abandoned
- 2005-07-26 AT AT05776414T patent/ATE396990T1/de not_active IP Right Cessation
- 2005-07-26 AR ARP050103099A patent/AR050184A1/es not_active Application Discontinuation
- 2005-07-26 CN CN2005800323948A patent/CN101027297B/zh not_active Expired - Fee Related
- 2005-07-26 DE DE602005007245T patent/DE602005007245D1/de active Active
- 2005-07-26 EP EP05776414A patent/EP1781644B1/en active Active
- 2005-07-26 WO PCT/US2005/026468 patent/WO2006014944A1/en active Application Filing
- 2005-07-26 JP JP2007523724A patent/JP2008508289A/ja active Pending
- 2005-07-26 ES ES05776414T patent/ES2306200T3/es active Active
- 2005-07-27 TW TW094125432A patent/TWI297337B/zh not_active IP Right Cessation
-
2007
- 2007-06-21 HK HK07106638A patent/HK1102328A1/xx not_active IP Right Cessation
-
2009
- 2009-10-01 US US12/571,840 patent/US8012953B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
US20100178294A1 (en) | 2010-07-15 |
US20060040948A1 (en) | 2006-02-23 |
ATE396990T1 (de) | 2008-06-15 |
EP1781644A1 (en) | 2007-05-09 |
HK1102328A1 (en) | 2007-11-16 |
ES2306200T3 (es) | 2008-11-01 |
US7652003B2 (en) | 2010-01-26 |
JP2008508289A (ja) | 2008-03-21 |
CA2575340A1 (en) | 2006-02-09 |
MX2007001102A (es) | 2007-04-13 |
CN101027297A (zh) | 2007-08-29 |
CN101027297B (zh) | 2010-09-08 |
EP1781644B1 (en) | 2008-05-28 |
DE602005007245D1 (es) | 2008-07-10 |
TWI297337B (en) | 2008-06-01 |
US8012953B2 (en) | 2011-09-06 |
TW200607807A (en) | 2006-03-01 |
WO2006014944A1 (en) | 2006-02-09 |
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