IS8509A - Ný 2-heteróarýl-setin bensímídasól afleiða - Google Patents

Ný 2-heteróarýl-setin bensímídasól afleiða

Info

Publication number
IS8509A
IS8509A IS8509A IS8509A IS8509A IS 8509 A IS8509 A IS 8509A IS 8509 A IS8509 A IS 8509A IS 8509 A IS8509 A IS 8509A IS 8509 A IS8509 A IS 8509A
Authority
IS
Iceland
Prior art keywords
heteroaryl
new
benzimidazole derivative
substituted benzimidazole
substituted
Prior art date
Application number
IS8509A
Other languages
English (en)
Inventor
Nonoshita Katsumasa
Ogino Yoshio
Ishikawa Makoto
Sakai Fumiko
Nakashima Hiroshi
Nagae Yoshikazu
Tsukahara Daisuke
Arakawa Keisuke
Nishimura Teruyuki
Eiki Junichi
Original Assignee
Banyu Pharma Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Banyu Pharma Co Ltd filed Critical Banyu Pharma Co Ltd
Publication of IS8509A publication Critical patent/IS8509A/is

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41961,2,4-Triazoles
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/04Anorexiants; Antiobesity agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • A61P5/48Drugs for disorders of the endocrine system of the pancreatic hormones
    • A61P5/50Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Emergency Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Urology & Nephrology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
IS8509A 2003-12-29 2006-06-15 Ný 2-heteróarýl-setin bensímídasól afleiða IS8509A (is)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP2003436992 2003-12-29
JP2004235696 2004-08-13
PCT/JP2004/019843 WO2005063738A1 (ja) 2003-12-29 2004-12-28 新規2-へテロアリール置換ベンズイミダゾール誘導体

Publications (1)

Publication Number Publication Date
IS8509A true IS8509A (is) 2006-06-15

Family

ID=34742165

Family Applications (1)

Application Number Title Priority Date Filing Date
IS8509A IS8509A (is) 2003-12-29 2006-06-15 Ný 2-heteróarýl-setin bensímídasól afleiða

Country Status (15)

Country Link
US (1) US7728025B2 (is)
EP (1) EP1702919B1 (is)
JP (1) JP4707560B2 (is)
KR (1) KR20060105872A (is)
AU (1) AU2004309287B2 (is)
BR (1) BRPI0418212A (is)
CA (1) CA2553160C (is)
EC (1) ECSP066682A (is)
IL (1) IL176451A0 (is)
IS (1) IS8509A (is)
MA (1) MA28336A1 (is)
NO (1) NO20063475L (is)
NZ (1) NZ548128A (is)
RU (1) RU2329261C2 (is)
WO (1) WO2005063738A1 (is)

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SE0102299D0 (sv) 2001-06-26 2001-06-26 Astrazeneca Ab Compounds
SE0102764D0 (sv) 2001-08-17 2001-08-17 Astrazeneca Ab Compounds
GB0226931D0 (en) 2002-11-19 2002-12-24 Astrazeneca Ab Chemical compounds
GB0226930D0 (en) 2002-11-19 2002-12-24 Astrazeneca Ab Chemical compounds
TW200600086A (en) 2004-06-05 2006-01-01 Astrazeneca Ab Chemical compound
KR20070085371A (ko) 2004-10-16 2007-08-27 아스트라제네카 아베 페녹시 벤즈아미드 화합물의 제조 방법
RU2398773C2 (ru) * 2004-11-02 2010-09-10 Баниу Фармасьютикал Ко., Лтд. Арилоксизамещенное производное бензимидазола
TW200714597A (en) 2005-05-27 2007-04-16 Astrazeneca Ab Chemical compounds
KR101346902B1 (ko) 2005-07-09 2014-01-02 아스트라제네카 아베 당뇨병 치료에 있어 glk 활성화제로서 사용하기 위한헤테로아릴 벤즈아미드 유도체
EP1905769B1 (en) * 2005-07-13 2017-03-29 Msd K.K. Heterocycle-substituted benzimidazole derivative
JP2007063225A (ja) * 2005-09-01 2007-03-15 Takeda Chem Ind Ltd イミダゾピリジン化合物
EP1928874A1 (en) * 2005-09-16 2008-06-11 AstraZeneca AB Heterobicyclic compounds as glucokinase activators
CA2624102A1 (en) 2005-09-29 2007-04-12 Sanofi-Aventis Phenyl- and pyridinyl- 1, 2 , 4 - oxadiazolone derivatives, processes for their preparation and their use as pharmaceuticals
US7625890B2 (en) 2005-11-10 2009-12-01 Smithkline Beecham Corp. Substituted imidazo[4,5-c]pyridine compounds as Akt inhibitors
EP1948614A2 (en) * 2005-11-18 2008-07-30 Takeda San Diego, Inc. Glucokinase activators
TW200738621A (en) 2005-11-28 2007-10-16 Astrazeneca Ab Chemical process
TW200732296A (en) * 2005-12-15 2007-09-01 Astrazeneca Ab Novel compounds
US7560551B2 (en) 2006-01-23 2009-07-14 Amgen Inc. Aurora kinase modulators and method of use
DK1984353T3 (en) * 2006-01-23 2016-03-14 Amgen Inc Aurorakinasemodulatorer and method of use
CA2649288C (en) 2006-04-19 2015-11-24 Novartis Ag 6-o-substituted benzoxazole and benzothiazole compounds and methods of inhibiting csf-1r signaling
PE20080251A1 (es) 2006-05-04 2008-04-25 Boehringer Ingelheim Int Usos de inhibidores de dpp iv
US8492405B2 (en) 2006-10-18 2013-07-23 Takeda Pharmaceutical Company Limited Glucokinase-activating fused heterocyclic compounds and methods of treating diabetes and obesity
TW200825063A (en) 2006-10-23 2008-06-16 Astrazeneca Ab Chemical compounds
TW200825060A (en) 2006-10-26 2008-06-16 Astrazeneca Ab Chemical compounds
KR20090090390A (ko) 2006-12-21 2009-08-25 아스트라제네카 아베 Glk 활성제로서 유용한 신규 결정 화합물
JPWO2008136428A1 (ja) * 2007-04-27 2010-07-29 武田薬品工業株式会社 含窒素5員複素環化合物
JP5301456B2 (ja) 2007-11-12 2013-09-25 Msd株式会社 ヘテロアリールオキシキナゾリン誘導体
PT2239253E (pt) 2008-02-06 2013-09-17 Daiichi Sankyo Co Ltd Novo derivado de fenilpirrole
PT2294066E (pt) 2008-04-28 2014-11-21 Janssen Pharmaceutica Nv Benzoimidazoles como inibidores da prolil-hidroxilase
EP2324028A2 (en) 2008-08-04 2011-05-25 AstraZeneca AB Therapeutic agents 414
US8592428B2 (en) 2008-08-15 2013-11-26 Msd K. K. Acetyl pyrrolidinyl indole derivative
CA2734981A1 (en) * 2008-08-29 2010-03-04 Banyu Pharmaceutical Co., Ltd. Oxotetrahydrofuran-2-yl-benzimidazole derivative
CA2738429C (en) * 2008-09-26 2016-10-25 Intellikine, Inc. Heterocyclic kinase inhibitors
GB0902434D0 (en) 2009-02-13 2009-04-01 Astrazeneca Ab Chemical process
GB0902406D0 (en) 2009-02-13 2009-04-01 Astrazeneca Ab Crystalline polymorphic form
AR076221A1 (es) * 2009-04-09 2011-05-26 Astrazeneca Ab Derivado de pirazol [4,5-e] pirimidina y su uso para tratar diabetes y obesidad
WO2010116177A1 (en) 2009-04-09 2010-10-14 Astrazeneca Ab A pyrazolo [4,5-e] pyrimidine derivative and its use to treat diabetes and obesity
UY32799A (es) 2009-07-24 2011-02-28 Novartis Ag Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos
KR20120115252A (ko) 2009-11-06 2012-10-17 벤더르빌트 유니버시티 Mglur4 알로스테릭 강화제로서 아릴 및 헤테로아릴 설폰, 조성물 및 신경 기능이상을 치료하는 방법
AU2010327597B2 (en) * 2009-12-04 2014-06-19 Nissan Chemical Industries, Ltd. 2-Pyridone compounds
MX2012006877A (es) 2009-12-18 2012-08-31 Idenix Pharmaceuticals Inc Inhibidores de virus de hepatitis c de arileno o heteroarileno 5, 5 - fusionado.
NZ600136A (en) 2009-12-31 2013-09-27 Novartis Ag Pyrazine derivatives and their use in the treatment of neurological disorders
DK2483255T3 (da) 2010-07-13 2014-01-20 Novartis Ag Oxazinderivater samt deres anvendelse ved behandling af neurologiske lidelser
CA2824097A1 (en) 2011-01-12 2012-07-19 Novartis Ag Oxazine derivatives and their use in the treatment of neurological disorders
WO2013063221A1 (en) 2011-10-25 2013-05-02 Janssen Pharmaceutica Nv Meglumine salt formulations of 1-(5,6-dichloro-1h-benzo[d]imidazol-2-yl)-1h-pyrazole-4-carboxylic acid
PL3417851T3 (pl) 2013-09-09 2020-12-14 Peloton Therapeutics, Inc. Etery arylowe i ich zastosowanie
US10278942B2 (en) 2015-03-11 2019-05-07 Peloton Therapeutics, Inc. Compositions for use in treating pulmonary arterial hypertension
WO2016144825A1 (en) 2015-03-11 2016-09-15 Peloton Therapeutics, Inc. Aromatic compounds and uses thereof
WO2016144826A1 (en) 2015-03-11 2016-09-15 Peloton Therapeutics, Inc. Substituted pyridines and uses thereof
US10512626B2 (en) 2015-03-11 2019-12-24 Peloton Therapeautics, Inc. Compositions for use in treating glioblastoma
WO2016168510A1 (en) 2015-04-17 2016-10-20 Peloton Therapeutics, Inc. Combination therapy of a hif-2-alpha inhibitor and an immunotherapeutic agent and uses thereof
ES2765738T3 (es) 2015-11-02 2020-06-10 Janssen Pharmaceutica Nv Compuesto de [1,2,4]triazolo[1,5-a]pirimidin-7-ilo
CA3038916A1 (en) 2016-11-02 2018-05-11 Janssen Pharmaceutica Nv [1,2,4]triazolo[1,5-a]pyrimidine compounds as pde2 inhibitors
MX385576B (es) 2016-11-02 2025-03-18 Janssen Pharmaceutica Nv Derivados de [1,2,4]triazol[1,5-a]pirimidina como inhibidores de pde2
AU2017353313C1 (en) 2016-11-02 2022-06-09 Janssen Pharmaceutica Nv (1,2,4)triazolo(1,5-a)pyrimidine compounds as PDE2 inhibitors
CA3226162A1 (en) 2021-07-09 2023-01-12 Plexium, Inc. Aryl compounds and pharmaceutical compositions that modulate ikzf2
WO2025111224A1 (en) * 2023-11-21 2025-05-30 Fmc Corporation Linked bicyclic compounds for controlling and combating invertebrate pests

Family Cites Families (18)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL134354C (is) * 1963-05-23
US3536809A (en) 1969-02-17 1970-10-27 Alza Corp Medication method
US3598123A (en) 1969-04-01 1971-08-10 Alza Corp Bandage for administering drugs
US3845770A (en) 1972-06-05 1974-11-05 Alza Corp Osmatic dispensing device for releasing beneficial agent
US3916899A (en) 1973-04-25 1975-11-04 Alza Corp Osmotic dispensing device with maximum and minimum sizes for the passageway
US4008719A (en) 1976-02-02 1977-02-22 Alza Corporation Osmotic system having laminar arrangement for programming delivery of active agent
EP0726260A1 (en) 1995-02-08 1996-08-14 American Cyanamid Company Herbicidal (1,2,4)thiadiazoles
PE92198A1 (es) 1996-08-01 1999-01-09 Banyu Pharma Co Ltd Derivados de 1,4-piperidina disustituida que contienen fluor
BR9907183A (pt) 1998-01-23 2003-06-10 Versicor Inc Colet neas combinatórias de oxazolidinona, composições e processos de preparação
JP2000026430A (ja) 1998-07-02 2000-01-25 Taisho Pharmaceut Co Ltd 2、5、6−置換ベンズイミダゾール化合物誘導体
RU2219172C2 (ru) * 1999-04-06 2003-12-20 Санкио Компани, Лимитед α-ЗАМЕЩЕННЫЕ ПРОИЗВОДНЫЕ КАРБОНОВЫХ КИСЛОТ
US7064215B2 (en) * 2001-07-03 2006-06-20 Chiron Corporation Indazole benzimidazole compounds
DE10238002A1 (de) 2002-08-20 2004-03-04 Merck Patent Gmbh Benzimidazolderivate
NZ540791A (en) 2003-02-13 2009-09-25 Banyu Pharma Co Ltd Novel 2-pyridinecarboxamide derivatives
US7432287B2 (en) 2003-02-26 2008-10-07 Banyu Pharmeceutical Co., Ltd. Heteroarylcarbamoylbenzene derivative
RU2398773C2 (ru) 2004-11-02 2010-09-10 Баниу Фармасьютикал Ко., Лтд. Арилоксизамещенное производное бензимидазола
TW200745031A (en) 2005-10-13 2007-12-16 Merck & Co Inc Acyl indoles, compositions containing such compounds and methods of use
TW200821284A (en) 2006-10-03 2008-05-16 Merck & Co Inc Glucagon receptor antagonist compounds, compositions containing such compounds and methods of use

Also Published As

Publication number Publication date
MA28336A1 (fr) 2006-12-01
BRPI0418212A (pt) 2007-04-27
ECSP066682A (es) 2006-10-25
JPWO2005063738A1 (ja) 2007-07-19
RU2006127420A (ru) 2008-02-10
EP1702919B1 (en) 2012-05-30
AU2004309287A1 (en) 2005-07-14
CA2553160A1 (en) 2005-07-14
EP1702919A4 (en) 2008-11-12
US20080070928A1 (en) 2008-03-20
NO20063475L (no) 2006-09-28
NZ548128A (en) 2010-05-28
CA2553160C (en) 2010-09-28
AU2004309287B2 (en) 2008-07-31
WO2005063738A1 (ja) 2005-07-14
RU2329261C2 (ru) 2008-07-20
IL176451A0 (en) 2006-10-05
US7728025B2 (en) 2010-06-01
JP4707560B2 (ja) 2011-06-22
KR20060105872A (ko) 2006-10-11
EP1702919A1 (en) 2006-09-20

Similar Documents

Publication Publication Date Title
IS8509A (is) Ný 2-heteróarýl-setin bensímídasól afleiða
IS7667A (is) Nýjar bensimídazólafleiður
DK1594840T3 (da) Piperidin-benzensulfonamid-derivater
ATE352550T1 (de) Chinazolinderivate
DE602004025020D1 (de) Baumaschine
ATE420066T1 (de) Amidoacetonitrilderivate
ATE553079T1 (de) Heteroarylphenylharnstoffderivat
ATE386518T1 (de) Benzimidazolderivate
ATE395345T1 (de) Imidazol-4-yl-ethynyl-pyridin-derivate
IS8180A (is) Nýjar besímídasólafleiður
DE602004008699D1 (de) Spitzenklöppelmaschine
DE50304148D1 (de) Handstichs gemaschine
DK1682129T3 (da) N-thiazol-2-ylbenzamidderivater
ATE457299T1 (de) 4-hydroxymethyl-1-aryl-cyclohexylamin-derivativ
DK1706373T3 (da) Amidoacetonitrilderivater
DE112004001791D2 (de) Bohrkopf
IS8045A (is) Púrín-6-ón-afleiður
DE10390324D2 (de) Geradeaus-Ziehmaschine
FI20040089L (fi) Palettijärjestely
ITMI20030161A1 (it) Lattometro a passaggio diretto
DE50304664D1 (de) Handstichs gemaschine
SE0303421L (sv) En list
ATE516273T1 (de) Insektizides spiroindanderivat
NO20030740D0 (no) Phenyl-derivative A
SE0301104D0 (sv) A new combination