AR047536A1 - Moduladores del receptor de quimioquina ccr5 - Google Patents
Moduladores del receptor de quimioquina ccr5Info
- Publication number
- AR047536A1 AR047536A1 ARP050100437A ARP050100437A AR047536A1 AR 047536 A1 AR047536 A1 AR 047536A1 AR P050100437 A ARP050100437 A AR P050100437A AR P050100437 A ARP050100437 A AR P050100437A AR 047536 A1 AR047536 A1 AR 047536A1
- Authority
- AR
- Argentina
- Prior art keywords
- alkyl
- aryl
- heteroaryl
- cycloalkyl
- independently
- Prior art date
Links
Classifications
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- 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
- C07D498/10—Spiro-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4747—Quinolines; Isoquinolines spiro-condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/537—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines spiro-condensed or forming part of bridged ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/538—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with carbocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Virology (AREA)
- General Chemical & Material Sciences (AREA)
- Tropical Medicine & Parasitology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
utiles en el tratamiento de una variedad de trastornos, incluyendo aquellos en que la modulacion de los receptores CCR5 está implicada. Los trastornos que se pueden tratar o prevenir mediante los presentes derivados incluyen VIH e infecciones retrovirales genéticamente relacionadas (y el resultante síndrome de inmunodeficiencia adquirida, SIDA), enfermedades del sistema inmune y enfermedades inflamatorias. Reivindicacion 1: Un compuesto de acuerdo con la formula (1), en donde: R2 es un grupo de formulas (2), A es (CH2)q; R1 es C(=O)R4, S(O)pR4, o C(=O)X, en donde X es NR5R6 o OR11; R2a y R2b son a) independientemente hidrogeno, C1-10 alquilo, C2-10 alquenilo, C1-10 haloalquilo, C3-7 cicloalquilo, (C3-7)cicloalquil-(C1-3)alquilo, C1-10 heteroalquilo, C1-10 alquilideno, C1-10 heteroalquilideno, arilo, aril-(C1-3)alquilo, heteroarilo, heteroaril-(C1-3)alquilo, C1-10 alquilo en donde 2 o 3 átomos de carbono no adyacentes son reemplazados independientemente con -O-, -S-, -NH- o - (CH2)wR8 en donde w es un numero entero de 2 a 6, y la cadena C2-6 alquileno opcionalmente contiene un doble enlace, -(CH2)wCH=NR9 en donde w es un numero entero de 2 a 6; o b) junto con los átomos de carbono a los que están unidos, son o-fenileno opcionalmente sustituido con 1 a 3 sustituyentes independientemente seleccionados del grupo consistente de C1-6 alquilo, C1-6 haloalquilo, C1-6 alcoxilo, C1-6 tioalquilo, C1-6 alquilsulfonilo, halogeno, NR5aR6a, ciano y nitro con la condicion que si R2a, R2b, junto con los átomos de carbono a los que están unidos son o-fenileno opcionalmente sustituido, m es 1; R3 es C1-10 alquilo, C2-10 alquenilo, C1-10 heteroalquilo, C3-7 cicloalquilo, C1-6 alquilheterociclo, arilo, aril-(C1-3)alquilo, heteroarilo, C1-6 alquil heteroarilo, C(=O)R3a en donde R3a es C1-10 alquilo, C2-10 alquenilo o C3-7 cicloalquilo, o un fragmento de grupo de formulas (3), R4 es C1-10 alquilo, C3-7 cicloalquil-(C1-10)alquilo sustituido, heterociclo, arilo, o heteroarilo; R5 y R6 son a) H, C1-10 alquilo, C1-10 heteroalquilo, C3-7 cicloalquilo, (C1-6)alquil-(C3-7)cicloalquilo, heterociclo-(C1-6)alquilo, arilo, aril-(C1-3)alquilo, heteroarilo, C1-6 alquil heteroarilo cuando se cogen independientemente; o b) C3-6 alquileno o [(CH2)]2O cuando son cogidos juntos; R5a y R6a son a) hidrogeno, C1-6 alquilo o C1-6 alquilcarbonilo cuando se cogen independientemente o b) C3-6 alquileno o [(CH2)]2O cuando se cogen juntos; R7 es hidrogeno, ciano o C1-6 alquilo; R8 es -CN, -NO2, -CONR5aR6a, COR9, -NHSO2(C1-6)alquilo; R9 es OH o C1-6 alcoxilo; R10 es N o N+-O-; R11 es C1-10 alquilo, C1-10 heteroalquilo, C3-7 cicloalquilo, (C1-6)alquil-(C3-7)cicloalquil, heterociclo-(C1-6)alquilo, arilo, aril-(C1- 3)alquilo, heteroarilo (C1-6)alquil-heteroarilo; m es 0 o 1; n es independientemente 0 a 2; o es independientemente 0 o 1; p es 0 a 2; q es 1 a 3; en donde: cada dicho heteroarilo se selecciona independientemente del grupo consistente de piridilo, 1- oxi-piridinilo, pirimidilo, oxipirimidinilo, pirazinilo, piridazinilo, pirrolilo, tienilo, furilo, imidazolilo, pirazolilo, oxazolilo, tiazolilo, isoxazolilo, isotiazolilo, indolinilo, N-Boc-indolinilo, quinolinilo, isoquinoli-nilo, benzofuranilo, 4,5,6,7-tetrahidrobenzofuranilo y 1,2,3,4-tetrahidroacridinilo; cada dicho arilo y dicho heteroarilo están opcionalmente independientemente sustituidos con 1 a 3 sustituyentes seleccionados del grupo consistente de hidroxilo, C1-6 alquilo, C1-6 haloalquilo, C1-6 alcoxilo, C1-6 haloalcoxilo, C1-6 tioalquilo, arilo, aril-(C1-3)alquilo, ariloxilo, heteroariloxilo, tioarilo, tioheteroarilo, aril-(C1-3)alcoxilo, heteroarilo, heterociclilo, C1-6 alquilheterociclo, C1-6 alquilsulfonilo, -NHSO2(C1- 6)alquilo, SO2NR5aR6a, (CH2)uCO2R9, (CH2)uCONR5aR6a, -X1C(=O)X2, C1-10 alquilcarbonilo, halogeno, NR5aR6a, ciano, nitro y C1-10 alquilo en donde 2 o 3 átomos de carbono no adyacentes son reemplazados independientemente con -O-, -S-, -NH- o NR5, en donde u es un numero entero de 0 a 6, X1 es NR6b o O; X2 es NR5R6 o OR3 y R5b es H o C1-6 alquilo; cada dicho heterociclo se selecciona independientemente del grupo consistente de pirrolidinilo, 1-metil-pirrolidinilo, piperidinilo, morfolinilo, tiomorfolinilo, tetrahidrofuranilo, dioxolanilo y piranilo opcionalmente sustituido con 1 a 3 sustituyentes independientemente seleccionados del grupo consistente de hidroxi-(C1-6)alquilo, C1-6 haloalquilo, C1-6 alcoxilo, C1-6 tioalquilo, C1-6 alquilsulfonilo, halogeno, NR5R6a, ciano y nitro; enantiomeros puros, enantiomeros parcialmente resueltos, mezclas racémicas, sales de adicion ácida farmacéuticamente aceptables, hidratos y solvatos de los mismos.
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US54340804P | 2004-02-10 | 2004-02-10 |
Publications (1)
Publication Number | Publication Date |
---|---|
AR047536A1 true AR047536A1 (es) | 2006-01-25 |
Family
ID=34837578
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ARP050100437A AR047536A1 (es) | 2004-02-10 | 2005-02-08 | Moduladores del receptor de quimioquina ccr5 |
Country Status (15)
Country | Link |
---|---|
US (2) | US7332500B2 (es) |
EP (1) | EP1716156A2 (es) |
JP (1) | JP2007522160A (es) |
KR (1) | KR100863854B1 (es) |
CN (1) | CN100497346C (es) |
AR (1) | AR047536A1 (es) |
AU (1) | AU2005211499A1 (es) |
BR (1) | BRPI0507586A (es) |
CA (1) | CA2554671A1 (es) |
CO (1) | CO5700742A2 (es) |
IL (1) | IL176720A0 (es) |
NO (1) | NO20063495L (es) |
RU (1) | RU2006132465A (es) |
TW (1) | TW200529857A (es) |
WO (1) | WO2005075484A2 (es) |
Families Citing this family (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6374762B1 (en) * | 1997-10-27 | 2002-04-23 | Correct Craft, Inc. | Water sport towing apparatus |
CN101031296A (zh) * | 2004-08-19 | 2007-09-05 | 弗特克斯药品有限公司 | 毒蕈碱受体调节剂 |
US7786141B2 (en) * | 2004-08-19 | 2010-08-31 | Vertex Pharmaceuticals Incorporated | Dihydrospiroindene modulators of muscarinic receptors |
CN101155587A (zh) * | 2004-11-29 | 2008-04-02 | 弗特克斯药品有限公司 | 毒蕈碱受体调节剂 |
NZ556629A (en) * | 2005-03-03 | 2010-04-30 | Janssen Pharmaceutica Nv | Substituted oxa-diaza-spiro-[5.5]-undecanone derivatives and their use as neurokinin antagonists |
BRPI0608847A2 (pt) | 2005-03-08 | 2010-02-02 | Janssen Pharmaceutica Nv | derivados de diaza-espiro-[4,4]-nonano substituìdos e seu uso como antagonistas de neurocinina |
WO2007045573A1 (en) | 2005-10-19 | 2007-04-26 | F. Hoffmann-La Roche Ag | Phenyl-acetamide nnrt inhibitors |
CN101374519A (zh) * | 2005-12-22 | 2009-02-25 | 弗特克斯药品有限公司 | 毒蕈碱性受体调节剂 |
RU2008137593A (ru) | 2006-02-22 | 2010-03-27 | Вертекс Фармасьютикалз Инкорпорейтед (Us) | Модуляторы мускариновых рецепторов |
AU2007221220A1 (en) * | 2006-02-22 | 2007-09-07 | Vertex Pharmaceuticals Incorporated | Spiro condensed piperidnes as modulators of muscarinic receptors |
US7858790B2 (en) * | 2006-06-29 | 2010-12-28 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
JP2010500412A (ja) * | 2006-08-15 | 2010-01-07 | バーテックス ファーマシューティカルズ インコーポレイテッド | ムスカリン受容体の調節剤 |
ATE503744T1 (de) | 2006-08-16 | 2011-04-15 | Hoffmann La Roche | Nicht-nukleosidische reverse-transkriptase-hemmer |
EP2051715A2 (en) | 2006-08-18 | 2009-04-29 | Vertex Pharmceuticals Incorporated | Modulators of muscarinic receptors |
KR101475091B1 (ko) | 2006-12-13 | 2014-12-22 | 에프. 호프만-라 로슈 아게 | 비뉴클레오시드 역전사 효소 억제제로서 2-(피페리딘-4-일)-4-페녹시- 또는 페닐아미노-피리미딘 유도체 |
EP2128163A1 (en) * | 2007-01-25 | 2009-12-02 | Takeda Pharmaceutical Company Limited | Spiro-ring compound |
EP2142555A1 (en) * | 2007-03-29 | 2010-01-13 | F. Hoffmann-Roche AG | Heterocyclic antiviral compounds |
US7977358B2 (en) * | 2007-07-26 | 2011-07-12 | Hoffmann-La Roche Inc. | Pyrazol derivatives |
WO2009037168A1 (en) * | 2007-09-19 | 2009-03-26 | F. Hoffmann-La Roche Ag | Heterocyclic antiviral compounds |
WO2009045519A1 (en) * | 2007-10-03 | 2009-04-09 | Vertex Pharmaceuticals Incorporated | Modulators of muscarinic receptors |
EP2285807A1 (en) * | 2008-05-09 | 2011-02-23 | F. Hoffmann-La Roche AG | Heterocyclic antiviral compounds |
EP2440251A4 (en) | 2009-06-09 | 2013-01-16 | Defyrus Inc | INTERFERON ADMINISTRATION FOR PROPHYLAXIS AGAINST PATHOGEN INFECTION OR TREATMENT OF PATHOGEN INFECTION |
WO2012171863A1 (en) * | 2011-06-16 | 2012-12-20 | Boehringer Ingelheim International Gmbh | New selective ccr2 antagonists |
JP6083818B2 (ja) | 2011-11-18 | 2017-02-22 | ヘプタレス セラピューティクス リミテッドHeptares Therapeutics Limited | ムスカリンm1受容体アゴニスト |
GB201404922D0 (en) | 2014-03-19 | 2014-04-30 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
LT3377500T (lt) * | 2015-11-16 | 2022-12-12 | Esteve Pharmaceuticals, S.A. | Oksadiazaspiro junginiai, skirti piktnaudžiavimo narkotikais arba priklausomybės nuo jų gydymui |
GB201617454D0 (en) | 2016-10-14 | 2016-11-30 | Heptares Therapeutics Limited | Pharmaceutical compounds |
TW201922758A (zh) | 2017-10-24 | 2019-06-16 | 美商歐樂根公司 | 烯胺及烯胺的非鏡像選擇性還原 |
GB201810239D0 (en) | 2018-06-22 | 2018-08-08 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
WO2020048826A1 (en) | 2018-09-03 | 2020-03-12 | Bayer Aktiengesellschaft | 5-substituted 1-oxa-3,9-diazaspiro[5.5]undecan-2-one compounds |
WO2020048828A1 (en) | 2018-09-03 | 2020-03-12 | Bayer Pharma Aktiengesellschaft | 5-heteroaryl-3,9-diazaspiro[5.5]undecane compounds |
WO2020048827A1 (en) | 2018-09-03 | 2020-03-12 | Bayer Aktiengesellschaft | 1, 3, 9-triazaspiro[5.5] undecan-2-one compounds |
GB201819960D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
US11629196B2 (en) | 2020-04-27 | 2023-04-18 | Incelldx, Inc. | Method of treating SARS-CoV-2-associated hypercytokinemia by administering a human monoclonal antibody (PRO-140) that inhibits CCR5/CCL5 binding interactions |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
NL127065C (es) * | 1964-04-22 | |||
HU204529B (en) * | 1989-08-10 | 1992-01-28 | Richter Gedeon Vegyeszet | Process for producing new 1-oxa-2-oxo-8-aza-spiro(4,5)decane derivatives and pharmaceutical compositions containing them |
CA2233204A1 (en) | 1995-09-29 | 1997-04-03 | Joseph A. Jakubowski | Spiro compounds as inhibitors of fibrinogen-dependent platelet aggregation |
US6689765B2 (en) * | 1999-05-04 | 2004-02-10 | Schering Corporation | Piperazine derivatives useful as CCR5 antagonists |
JP3722700B2 (ja) * | 1999-05-04 | 2005-11-30 | シェーリング コーポレイション | Ccr5アンタゴニストとして有用なピペラジン誘導体 |
US6391865B1 (en) * | 1999-05-04 | 2002-05-21 | Schering Corporation | Piperazine derivatives useful as CCR5 antagonists |
ES2246233T3 (es) | 1999-05-04 | 2006-02-16 | Schering Corporation | Derivados de piperidina utiles como antagonistas de ccr5. |
MXPA02005465A (es) | 1999-12-03 | 2003-10-15 | Ono Pharmaceutical Co | Derivados de triazaspiro(5.5)undecano y composiciones farmaceuticas que los comprenden, como un ingrediente activo. |
AU2001230537A1 (en) | 2000-02-01 | 2001-08-14 | Daiichi Pharmaceutical Co., Ltd. | Pyridoxazine derivatives |
AU2001243394A1 (en) * | 2000-03-02 | 2001-09-12 | Smith Kline Beecham Corporation | Compounds and methods |
CA2447329C (en) * | 2001-05-14 | 2009-07-28 | F.Hoffmann-La Roche Ag | 1-oxa-3,9-diaza-spiro[5,5]undecan-2-ones derivatives and its use as antagonist of the neurikinin receptor |
NZ571695A (en) * | 2001-12-28 | 2010-02-26 | Acadia Pharm Inc | Spiroazacyclic compounds as monoamine receptor for modulating 5-HT2A receptor-mediated events |
-
2005
- 2005-02-01 KR KR1020067016037A patent/KR100863854B1/ko not_active IP Right Cessation
- 2005-02-01 CN CNB2005800045181A patent/CN100497346C/zh not_active Expired - Fee Related
- 2005-02-01 BR BRPI0507586-6A patent/BRPI0507586A/pt not_active IP Right Cessation
- 2005-02-01 CA CA002554671A patent/CA2554671A1/en not_active Abandoned
- 2005-02-01 WO PCT/EP2005/000976 patent/WO2005075484A2/en active Application Filing
- 2005-02-01 AU AU2005211499A patent/AU2005211499A1/en not_active Abandoned
- 2005-02-01 JP JP2006552503A patent/JP2007522160A/ja active Pending
- 2005-02-01 EP EP05707116A patent/EP1716156A2/en not_active Withdrawn
- 2005-02-01 RU RU2006132465/04A patent/RU2006132465A/ru not_active Application Discontinuation
- 2005-02-05 TW TW094103869A patent/TW200529857A/zh unknown
- 2005-02-08 AR ARP050100437A patent/AR047536A1/es unknown
- 2005-02-10 US US11/055,642 patent/US7332500B2/en not_active Expired - Fee Related
-
2006
- 2006-07-05 IL IL176720A patent/IL176720A0/en unknown
- 2006-07-31 CO CO06074877A patent/CO5700742A2/es not_active Application Discontinuation
- 2006-07-31 NO NO20063495A patent/NO20063495L/no not_active Application Discontinuation
-
2008
- 2008-01-11 US US12/008,452 patent/US7538122B2/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
US7538122B2 (en) | 2009-05-26 |
KR100863854B1 (ko) | 2008-10-15 |
EP1716156A2 (en) | 2006-11-02 |
BRPI0507586A (pt) | 2007-07-03 |
AU2005211499A1 (en) | 2005-08-18 |
CN100497346C (zh) | 2009-06-10 |
CA2554671A1 (en) | 2005-08-18 |
KR20060108770A (ko) | 2006-10-18 |
CO5700742A2 (es) | 2006-11-30 |
IL176720A0 (en) | 2006-10-31 |
TW200529857A (en) | 2005-09-16 |
NO20063495L (no) | 2006-11-01 |
JP2007522160A (ja) | 2007-08-09 |
US7332500B2 (en) | 2008-02-19 |
US20080139544A1 (en) | 2008-06-12 |
RU2006132465A (ru) | 2008-03-20 |
WO2005075484A3 (en) | 2005-10-20 |
WO2005075484A2 (en) | 2005-08-18 |
US20050176703A1 (en) | 2005-08-11 |
CN1918171A (zh) | 2007-02-21 |
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