HU224443B1 - Fluor-alkoxi-benzaldehid-származékok - Google Patents

Fluor-alkoxi-benzaldehid-származékok Download PDF

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HU224443B1
HU224443B1 HU9500836A HU9500836A HU224443B1 HU 224443 B1 HU224443 B1 HU 224443B1 HU 9500836 A HU9500836 A HU 9500836A HU 9500836 A HU9500836 A HU 9500836A HU 224443 B1 HU224443 B1 HU 224443B1
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pct
compounds
trifluoromethoxy
phenyl
difluoromethoxy
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HUT70499A (en
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John Adams Lowe Iii.
Terry Jay Rosen
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Pfizer Inc.
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Abstract

A találmány tárgya (XIA), (XIB) és (XIC) képletű vegyületek – ahol R14jelentése trifluor-metoxi- vagy difluor-metoxi- csoport, R15 jelentése1–4 szénatomos alkilcsoport, R16 jelentése difluor-metoxi- vagy 1–4szénatomos alkilcsoport és R17 jelentése trifluor-metoxi-, difluor-metoxi-, 1–4 szénatomos alkil- vagy 1–4 szénatomos alkoxicsoport.

Description

A leírás terjedelme 4 oldal (ezen belül 1 lap ábra)
HU 224 443 Β1
A jelen találmány tárgya a (ΧΙΑ), (XIB) vagy (XIC) általános képletű vegyületek.
A képletben
R14 jelentése trifluor-metoxi- vagy difluor-metoxi-csoport, 5
R15 jelentése 1-4 szénatomos alkilcsoport,
R16 jelentése difluor-metoxi- vagy 1-4 szénatomos alkilcsoport és
R17 jelentése trifluor-metoxi-, difluor-metoxi-, 1-4 szénatomos alkil- vagy 1-4 szénatomos alkoxicsoport. 10 A találmány szerinti vegyületek intermedierjei a
221 634 lajstromszámú magyar szabadalmi leírásunkban védett P anyag receptor antagonista hatású (I) általános képletű nitrogéntartalmú heterociklusos vegyületek fluor-alkoxi-benzil-amino-származékainak - ahol 15 X1 jelentése adott esetben egy-három fluoratommal szubsztituált 1-6 szénatomos alkoxicsoport vagy hidroxilcsoport,
X2 jelentése hidrogénatom vagy 1-3 fluoratommal helyettesített 1-6 szénatomos alkoxicsoport, 20
X3 hidrogén- vagy halogénatom, nitrocsoport,
1-6 szénatomos alkilcsoport, adott esetben egy-három fluoratommal szubsztituált 1-6 szénatomos alkoxicsoport, vagy 1-6 szénatomos alkil-amino-, vagy 1-6 szénatomos alkilcsoportot tar- 25 talmazó dialkil-amino-csoport, vagy
O
II
1-6 szénatomos alkil-C-ΝΗ-, és
Q jelentése (III) vagy (VII) általános képletű csoport, 30 ahol
R2 jelentése hidrogénatom,
R3 jelentése benzhidrilcsoport vagy egy-három fluoratommal fluorozott 1-6 szénatomos alkoxicsoporttal szubsztituált fenilcsoport, 35
X jelentése (CH2)q, ahol q értéke 1-6, m értéke 0-8, és ha rrwO, R10 és R11 1-6 szénatomos alkoxicsoport,
R6 jelentése adott esetben két halogénatommal 40 szubsztituált fenilcsoport vagy az alkoxirészben egy-három fluoratommal szubsztituált (1-6 szénatomos alkoxi)-fenil-csoport,
R7, R8 és R9 jelentése hidrogénatom, azzal a megkötéssel, hogy ha a (VII) általános kép- 45 letben m jelentése 0, R11 nincs jelen, és R10 hidrogénatom, ami nitrogénhez kapcsolódik, és ha X1, X2 vagy X3 közül egyik se jelent fluorozott alkoxicsoportot, akkor R6 fluorozott alkoxicsoporttal szubsztituált fenilcsoport, vagy ha a (III) általános képletben X1, X2 és X3 közül egyik sem fluorozott alkoxicsoport, akkor R3 jelentése fluorozott alkoxicsoporttal helyettesített fenilcsoport.
A találmány szerinti (XIA), (XIB) és (XIC) általános képletű vegyületeket az irodalomból ismert módon állíthatjuk elő a megfelelő paraszubsztituált benzolok aldehiddé alakításával.
A (XIA), (XIB), (XIC) általános képletű vegyületek előállítását az alábbi példával illusztráljuk.
1. példa
2-Metoxi-5-trifluor-metoxi-benzaldehid
Nitrogénatmoszférában egy gömblombikba helyezünk 3,63 ml, 28 mmol 4-trifluor-metoxi-fenolt és 25 ml acetont. A keverés alatt lévő oldathoz hozzáadunk 7,75 g, 56 mmol kálium-karbonátot és 3,48 ml, 56 mmol metil-jodidot, és a reakcióelegyet szobahőmérsékleten egész éjjel keverjük. A szilárd anyagot leszívatjuk, a szűrési lepényt acetonnal öblítjük. A szűrletet bepárolva 6,5 g szilárd anyag és olaj keveréket kapunk. Az elegyet kloroformmal hígítjuk, leszűrjük, a szűrletet bepároljuk. 5,5 g 1-metoxi-4-trifluor-metoxibenzolt kapunk sárga olaj formájában.
1H-NMR (CDCI3): δ 3,78 (s, 3H), 6,83 (d, 1H, J=12),
7,10 (d, 1H, J=12).
Tömegspektrum m/z: 192 (szülő).
Nitrogénatmoszférában egy gömblombikba helyezünk 5,5 g, 29 mmol 1-metoxi-4-trifluor-metoxi-benzolt és 110 ml diklór-metánt. A rendszerhez, melyet jég és aceton hűtőfürdővel hűtünk, hozzáadunk 3,77 ml, 34 mmol titán-tetrakloridot 1 perc alatt. A reakcióelegyet 30 percig keverjük, és a rendszerhez 5,69 ml, 63 mmol α,α-diklór-metil-metil-étert adunk. A jeges fürdőt hagyjuk megszűnni, és az elegyet szobahőmérsékleten egész éjjel keverjük. Az elegyet óvatosan vízbe öntjük, és három részlet diklór-metánnal extraháljuk. Az egyesített extraktumokat vízzel és telített sóoldattal mossuk, nátrium-szulfát felett szárítjuk, bepároljuk. 6,06 g olajat kapunk. A nyersanyagot gyorskromatográfiásan 250 g szilikagélen tisztítjuk, eluálószerként etil-acetát és hexán 1:9 arányú elegyét használjuk. 920 mg cím szerinti vegyületet kapunk, amely enyhén szennyezett, és 3,27 g tiszta cím szerinti vegyületet kapunk.
1 H-NMR (CDCI3): δ 3,94 (s, 3H), 7,00 (d, 1H, J=9),
7,38 (dd, 1H, J=3,9), 7,66 (d, 1H, J=3), 10,4 (s, 1H). Tömegspektrum: m/z: 220 (szülő).
A találmány szerinti aldehidek előállításánál a reakció folyamatát az 1. táblázat mutatja.
1. táblázat (XIA), (XIB), (XIC) általános képletű vegyületek előállítása
-C6H2R14OR15 -c6h2r16ocf3 -c6h2r17ochf2 Kiindulási anyag Reagensek*
5-Terc-butil-2-trifluor-metoxi-fenil trifluor-metoxi-benzol 9, h
2-Etoxi-5-trifluor-metoxi-fenil 4-trifluor-metoxi-fenol i, a
2-Difluor-metoxi-5-trifluor-metoxi-fenil 2-hidroxi-5-trifluor-metoxi-benzaldehid j
HU 224 443 Β1
1. táblázat (folytatás)
-C6H2R14OR15 -c6h2r16ocf3 -c6h2r17ochf2 Kiindulási anyag Reagensek*
2-lzopropoxi-5-trifluor-metoxi-fenil 4-trifluor-metoxi-fenol k, a
5-Terc-butil-2-difluor-metoxi-fenil 4-terc-butil-fenol a.j
2,5-bisz(Difluor-metoxi)-fenil 2,5-dihidroxi-benzaldehid j
2-Difluor-metoxi-5-izopropil-fenil 4-izopropil-fenol a.j
2-Difluor-metoxi-5-etil-fenil 4-etil-metoxi-benzol a, f, j
2-Metoxi-5-trifluor-metoxi-fenil 4-trifluor-metoxi-fenol b, a
2-Difluor-metoxi-5-metil-fenil 5-metil-2-metoxi-benzaldehid f.j
* A reagensek a (ΧΙΑ), (XIB) és (XIC) képletű vegyületek előállításánál a standard úton:
a) CI2CHOCH3, TiCI4
b) metil-jodid
f) BBr3
g) terc-butil-klorid/AICI3
h) CI2CHOCH3/AICI3
i) etil-jodid
j) CIF2CH
k) izopropil-bromid

Claims (1)

  1. SZABADALMI IGÉNYPONT (XIA), (XIB) és (XIC) általános képletű vegyületek ahol R14 jelentése trifluor-metoxi- vagy difluor-metoxi-csoport, R15 jelentése 1-4 szénatomos alkilcsoport,
    R16 jelentése difluor-metoxi- vagy 1-4 szénatomos alkilcsoport és R17 jelentése trifluor-metoxi-, difluor-metoxi-, 1-4 szénatomos alkil- vagy 1-4 szénatomos alkoxicsoport.
HU9500836A 1991-06-20 1992-05-05 Fluor-alkoxi-benzaldehid-származékok HU224443B1 (hu)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US71794391A 1991-06-20 1991-06-20
HU9303668A HU221634B1 (hu) 1991-06-20 1992-05-05 Nitrogéntartalmú heterociklusos vegyületek fluor-alkoxi-benzilamino-származékai, eljárás előállításukra és az ezeket tartalmazó gyógyszerkészítmények
PCT/US1992/003571 WO1993000331A1 (en) 1991-06-20 1992-05-05 Fluoroalkoxybenzylamino derivatives of nitrogen containing heterocycles

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HU9500836D0 HU9500836D0 (en) 1995-05-29
HUT70499A HUT70499A (en) 1995-10-30
HU224443B1 true HU224443B1 (hu) 2005-09-28

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HU9303668A HU221634B1 (hu) 1991-06-20 1992-05-05 Nitrogéntartalmú heterociklusos vegyületek fluor-alkoxi-benzilamino-származékai, eljárás előállításukra és az ezeket tartalmazó gyógyszerkészítmények
HU9500836A HU224443B1 (hu) 1991-06-20 1992-05-05 Fluor-alkoxi-benzaldehid-származékok

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Families Citing this family (86)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5364943A (en) * 1991-11-27 1994-11-15 Pfizer Inc. Preparation of substituted piperidines
CA2109613C (en) * 1991-06-20 1996-11-19 John Adams Lowe Iii Fluoroalkoxybenzylamino derivatives of nitrogen containing heterocycles
EP0533280B2 (en) 1991-09-20 2004-12-01 Glaxo Group Limited Novel medical use for tachykinin antagonists
ES2164657T3 (es) * 1992-05-18 2002-03-01 Pfizer Derivados aza-biciclicos puenteados como antagonistas de la sustancia p.
WO1994003445A1 (en) * 1992-08-04 1994-02-17 Pfizer Inc. 3-benzylamino-2-phenyl-piperidine derivatives as substance p receptor antagonists
ATE208376T1 (de) * 1992-08-19 2001-11-15 Pfizer Substituierte benzylamin-stickstoff enthaltende nichtaromatische heterocyclen
FR2700472B1 (fr) 1993-01-19 1995-02-17 Rhone Poulenc Rorer Sa Association synergisante ayant un effet antagoniste des récepteurs NK1 et NK2.
GB9305718D0 (en) 1993-03-19 1993-05-05 Glaxo Group Ltd Medicaments
JP2822274B2 (ja) * 1993-05-19 1998-11-11 ファイザー製薬株式会社 Ｐ物質拮抗剤としてのヘテロ原子置換アルキルベンジルアミノキヌクリジン類
IL109646A0 (en) * 1993-05-19 1994-08-26 Pfizer Heteroatom substituted alkyl benzylamino-quinuclidines
EP0700384B1 (en) * 1993-05-28 1997-07-16 Pfizer Inc. Process for preparing and resolving 2-phenyl-3-aminopiperidine
US5393762A (en) * 1993-06-04 1995-02-28 Pfizer Inc. Pharmaceutical agents for treatment of emesis
EP0719253B1 (en) * 1993-09-17 2004-04-28 Pfizer Inc. 3-amino-5-carboxy-substituted piperidines and 3-amino-4-carboxy-substituted pyrrolidines as tachykinin antagonists
US6083943A (en) * 1993-09-17 2000-07-04 Pfizer Inc Substituted azaheterocyclecarboxylic acid
EP1209157A1 (en) * 1993-09-17 2002-05-29 Pfizer Inc. Heteroarylamino and heteroarylsulfonamido substituted 3-benzylaminomethyl piperidines and related compounds
IL111002A (en) * 1993-09-22 1998-09-24 Glaxo Group Ltd History of piperidine, their preparation and the pharmaceutical preparations containing them
EP0653208A3 (en) * 1993-11-17 1995-10-11 Pfizer Substance P antagonists for the treatment or prevention of sunburn.
EP0659409A3 (en) * 1993-11-23 1995-08-09 Pfizer Substance P antagonists for the inhibition of angiogenesis.
EP0655246A1 (en) * 1993-11-30 1995-05-31 Pfizer Inc. Substance P antagonists for the treatment of disorders caused by helicobacter pylori or other spiral urease-positive gram-negative bacteria
FR2728166A1 (fr) 1994-12-19 1996-06-21 Oreal Composition topique contenant un antagoniste de substance p
FR2728165A1 (fr) 1994-12-19 1996-06-21 Oreal Utilisation d'un antagoniste de substance p pour le traitement des rougeurs cutanees d'origine neurogene
FR2728169A1 (fr) 1994-12-19 1996-06-21 Oreal Utilisation d'un antagoniste de substance p pour le traitement des prurits et des dysesthesies oculaires ou palpebrales
ATE279406T1 (de) * 1995-01-12 2004-10-15 Glaxo Group Ltd Piperidinderivate mit tachykinin-antagonistischer wirkung
GB9505692D0 (en) * 1995-03-21 1995-05-10 Glaxo Group Ltd Chemical compounds
TW340842B (en) * 1995-08-24 1998-09-21 Pfizer Substituted benzylaminopiperidine compounds
DE69603615T2 (de) 1995-10-10 2000-02-17 Pfizer Nk-1 rezeptor antagonisten in neurogener entzündung in gen-therapie
TW458774B (en) 1995-10-20 2001-10-11 Pfizer Antiemetic pharmaceutical compositions
FR2741262B1 (fr) 1995-11-20 1999-03-05 Oreal Utilisation d'un antagoniste de tnf-alpha pour le traitement des rougeurs cutanees d'origine neurogene
DE69623580T2 (de) 1995-12-21 2003-01-09 Pfizer 3-((5-Substituierte Benzyl)Amino)-2-Phenylpiperidine als Substance-P-Antagonisten
US6329396B1 (en) 1996-06-10 2001-12-11 Pfizer Inc. Substituted benzylaminopiperidine compounds
MX9706196A (es) * 1996-08-14 1998-02-28 Pfizer Compuestos triciclicos de piperidinilamino como antagonistas de la sustancia p.
US5750549A (en) * 1996-10-15 1998-05-12 Merck & Co., Inc. Cycloalkyl tachykinin receptor antagonists
NZ329807A (en) * 1997-04-23 2000-07-28 Pfizer NK-1 receptor antagonists and P receptor antagonists 2-Diarylmethyl-3-amino-1-azabicyclo[2.2.2]octane derivatives and amino substituted N-containing rings as agents for treating irritable bowel syndrome
KR19990030614A (ko) * 1997-10-02 1999-05-06 성재갑 스쿠알렌 합성 효소 억제활성을 갖는 신규 화합물, 그의 제조방법 및 그를 포함하는 조성물
RS49964B (sr) 1999-05-17 2008-09-29 Pfizer Products Inc., Postupak za dobijanje 2-fenil-3-aminopiridina,njegovih supstituisanih fenil derivata, i njegovih soli
JP2001172178A (ja) * 1999-10-25 2001-06-26 Pfizer Prod Inc 偏頭痛治療用のｎｋ−１レセプターアンタゴニスト及びエレトリプタン
CN1414953A (zh) 1999-11-03 2003-04-30 阿尔巴尼分子研究公司 芳基和杂芳基取代的四氢异喹啉及其阻断去甲肾上腺素、多巴胺和5－羟色胺重摄取的用途
US7163949B1 (en) 1999-11-03 2007-01-16 Amr Technology, Inc. 4-phenyl substituted tetrahydroisoquinolines and use thereof
AU7334901A (en) 2000-07-11 2002-01-21 Du Pont Pharm Co Novel 4-phenyl substituted tetrahydroisoquinolines and therapeutic use thereof
US20020049211A1 (en) * 2000-09-06 2002-04-25 Sobolov-Jaynes Susan Beth Combination treatment for depression and anxiety
EP1192952A3 (en) * 2000-09-28 2003-03-26 Pfizer Products Inc. Combination, for treating depression and anxiety, containing an NK-3 receptor antagonist and a CNS penetrant NK-1 receptor antagonist
HUP0401154A2 (hu) * 2001-07-20 2004-10-28 Pfizer Products Inc. NK-1 receptor antagonisták használata kutyák, macskák és lovak nemkívánatos viselkedésének módosítására
US6686507B2 (en) 2002-03-06 2004-02-03 Pfizer Inc Purification of 2-methoxy-5-trifluoromethoxybenzaldehyde
US6911544B2 (en) 2002-10-23 2005-06-28 Pfizer Inc. Process for the preparation of (S,S)-cis-2-phenyl-3-aminopiperidine
US20040204455A1 (en) * 2003-04-10 2004-10-14 Cody Wayne Livingston Piperidine derivative rennin inhibitors
WO2005051919A1 (en) * 2003-11-26 2005-06-09 Pfizer Products Inc. Aminopyrazole derivatives as gsk-3 inhibitors
MX2007000428A (es) 2004-07-15 2008-03-05 Amr Technology Inc Tetrahidroisoquinolinas sustituidas con arilo y heteroarilo y uso de las mismas para bloquear la captacion de norepinefrina, dopamina y serotonina.
ATE550019T1 (de) 2005-05-17 2012-04-15 Merck Sharp & Dohme Cis-4-ä(4-chlorophenyl)sulfonylü-4-(2,5- difluorophenyl)cyclohexanepropansäure zur behandlug von krebs
CA2615403C (en) 2005-07-15 2015-06-16 Amr Technology, Inc. Aryl-and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
AU2006297443B2 (en) 2005-09-29 2010-08-12 Merck Sharp & Dohme Corp. Acylated spiropiperidine derivatives as melanocortin-4 receptor modulators
GB0603041D0 (en) 2006-02-15 2006-03-29 Angeletti P Ist Richerche Bio Therapeutic compounds
CA2664113C (en) 2006-09-22 2013-05-28 Merck & Co., Inc. Use of platencin and platensimycin as fatty acid synthesis inhibitors to treat obesity, diabetes and cancer
US20110218176A1 (en) 2006-11-01 2011-09-08 Barbara Brooke Jennings-Spring Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
EP2109608B1 (en) 2007-01-10 2011-03-23 Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A. Amide substituted indazoles as poly(adp-ribose)polymerase (parp) inhibitors
CN101641099A (zh) 2007-01-24 2010-02-03 葛兰素集团有限公司 包含3,5-二氨基-6-(2,3-二氯苯基)-1,2,4-三嗪或r(-)-2,4-二氨基-5-(2,3-二氯苯基)-6-氟甲基嘧啶和nk1的药物组合物
US8106086B2 (en) 2007-04-02 2012-01-31 Msd K.K. Indoledione derivative
JP5501227B2 (ja) 2007-06-27 2014-05-21 メルク・シャープ・アンド・ドーム・コーポレーション ヒストンデアセチラーゼ阻害剤としての４−カルボキシベンジルアミノ誘導体
TWI410650B (zh) * 2007-11-09 2013-10-01 Hon Hai Prec Ind Co Ltd 轉接板
AU2009222122A1 (en) 2008-03-03 2009-09-11 Tiger Pharmatech Tyrosine kinase inhibitors
US9156812B2 (en) 2008-06-04 2015-10-13 Bristol-Myers Squibb Company Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine
UA105182C2 (ru) 2008-07-03 2014-04-25 Ньюрексон, Інк. Бензоксазины, бензотиазины и родственные соединения, которые имеют ингибирующую nos активность
EP2413932A4 (en) 2009-04-01 2012-09-19 Merck Sharp & Dohme INHIBITORS OF AKT ACTIVITY
ES2662072T3 (es) 2009-05-12 2018-04-05 Albany Molecular Research, Inc. 7-([1,2,4]triazolo[1,5-a]piridin-6-il)-4-(3,4-diclorofenil)-1,2,3,4-tetrahidroisoquinolina y uso de la misma
EP2429293B1 (en) 2009-05-12 2014-10-29 Bristol-Myers Squibb Company CRYSTALLINE FORMS OF (S)-7-([1,2,4]TRIAZOLO[1,5-a]PYRIDIN-6-YL)-4-(3,4-DICHLOROHPHENYL)-1,2,3,4-TETRAHYDROISOQUINOLINE AND USE THEREOF
KR20120034644A (ko) 2009-05-12 2012-04-12 알바니 몰레큘라 리써치, 인크. 아릴, 헤테로아릴, 및 헤테로사이클 치환된 테트라하이드로이소퀴놀린 및 이의 용도
KR101485645B1 (ko) 2009-10-14 2015-01-22 머크 샤프 앤드 돔 코포레이션 ｐ53 활성을 증가시키는 치환된 피페리딘 및 그의 용도
WO2011163330A1 (en) 2010-06-24 2011-12-29 Merck Sharp & Dohme Corp. Novel heterocyclic compounds as erk inhibitors
CN107090456B (zh) 2010-08-02 2022-01-18 瑟纳治疗公司 使用短干扰核酸的RNA干扰介导的联蛋白（钙粘蛋白关联蛋白质），β1基因表达的抑制
HUE044815T2 (hu) 2010-08-17 2019-11-28 Sirna Therapeutics Inc Hepatitisz B vírus (HBV) génexpressziójának RNS-interferencia közvetített gátlása, rövid interferáló nukleinsav (SINS) alkalmazásával
US8883801B2 (en) 2010-08-23 2014-11-11 Merck Sharp & Dohme Corp. Substituted pyrazolo[1,5-a]pyrimidines as mTOR inhibitors
WO2012030685A2 (en) 2010-09-01 2012-03-08 Schering Corporation Indazole derivatives useful as erk inhibitors
US9242981B2 (en) 2010-09-16 2016-01-26 Merck Sharp & Dohme Corp. Fused pyrazole derivatives as novel ERK inhibitors
WO2012058210A1 (en) 2010-10-29 2012-05-03 Merck Sharp & Dohme Corp. RNA INTERFERENCE MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACIDS (siNA)
US9351965B2 (en) 2010-12-21 2016-05-31 Merck Sharp & Dohme Corp. Indazole derivatives useful as ERK inhibitors
CN103732592A (zh) 2011-04-21 2014-04-16 默沙东公司 胰岛素样生长因子-1受体抑制剂
US9023865B2 (en) 2011-10-27 2015-05-05 Merck Sharp & Dohme Corp. Compounds that are ERK inhibitors
EP3919620A1 (en) 2012-05-02 2021-12-08 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
CA2882950A1 (en) 2012-09-28 2014-04-03 Merck Sharp & Dohme Corp. Novel compounds that are erk inhibitors
EP2919788A4 (en) 2012-11-14 2016-05-25 Univ Johns Hopkins METHODS AND COMPOSITIONS FOR THE TREATMENT OF SCHIZOPHRENIA
LT2925888T (lt) 2012-11-28 2018-01-10 Merck Sharp & Dohme Corp. Vėžio gydymo kompozicijos ir būdai
BR112015013611A2 (pt) 2012-12-20 2017-11-14 Merck Sharp & Dohme composto, e, composição farmacêutica
WO2014120748A1 (en) 2013-01-30 2014-08-07 Merck Sharp & Dohme Corp. 2,6,7,8 substituted purines as hdm2 inhibitors
US20160194368A1 (en) 2013-09-03 2016-07-07 Moderna Therapeutics, Inc. Circular polynucleotides
US10947234B2 (en) 2017-11-08 2021-03-16 Merck Sharp & Dohme Corp. PRMT5 inhibitors
US20210309688A1 (en) 2018-08-07 2021-10-07 Merck Sharp & Dohme Corp. Prmt5 inhibitors
US20210277009A1 (en) 2018-08-07 2021-09-09 Merck Sharp & Dohme Corp. Prmt5 inhibitors

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3452026A (en) * 1966-03-15 1969-06-24 Bristol Myers Co Substituted 1,2,3,4-tetrahydroquinolines
US3560510A (en) * 1969-03-05 1971-02-02 Aldrich Chem Co Inc 2-benzhydrylquinuclidines
MX18467A (es) * 1988-11-23 1993-07-01 Pfizer Agentes terapeuticos de quinuclidinas
US5232929A (en) * 1990-11-28 1993-08-03 Pfizer Inc. 3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use
WO1991009844A1 (en) * 1990-01-04 1991-07-11 Pfizer Inc. Substance p antagonists
DK0532527T3 (da) * 1990-06-01 1995-01-02 Pfizer 3-amino-2-arylquinuclidiner, fremgangsmåde til fremstilling deraf og farmaceutiske præparater indeholdende disse
CA2086434C (en) * 1990-07-23 1998-09-22 John A. Lowe, Iii Quinuclidine derivatives
CA2089736A1 (en) * 1990-09-28 1992-03-29 Manoj C. Desai Fused ring analogs of nitrogen containing nonaromatic heterocycles
CA2093322C (en) * 1990-10-03 2002-01-29 Jonathan H. Hodgkin Epoxy resins based on diaminobisimide compounds
US5138060A (en) * 1991-01-03 1992-08-11 Pfizer Inc. Process and intermediates for preparing azabicyclo(2.2.2)octan-3-imines
RU2105001C1 (ru) * 1991-03-26 1998-02-20 Пфайзер Инк. Способ получения замещенных 3-аминопиперидинов
ATE211743T1 (de) * 1991-05-22 2002-01-15 Pfizer Substituierte 3-aminochinuclidine
DE9290063U1 (de) * 1991-05-31 1994-02-24 Pfizer Chinuclidin-Derivate
CA2109613C (en) * 1991-06-20 1996-11-19 John Adams Lowe Iii Fluoroalkoxybenzylamino derivatives of nitrogen containing heterocycles
WO1994003445A1 (en) * 1992-08-04 1994-02-17 Pfizer Inc. 3-benzylamino-2-phenyl-piperidine derivatives as substance p receptor antagonists
US5393762A (en) * 1993-06-04 1995-02-28 Pfizer Inc. Pharmaceutical agents for treatment of emesis
US5576317A (en) * 1994-12-09 1996-11-19 Pfizer Inc. NK-1 receptor antagonists and 5HT3 receptor antagonists for the treatment of emesis

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