SV2016005257A - Benzimidazol-2-aminas como inhibidores de midh1 - Google Patents

Benzimidazol-2-aminas como inhibidores de midh1

Info

Publication number
SV2016005257A
SV2016005257A SV2016005257A SV2016005257A SV2016005257A SV 2016005257 A SV2016005257 A SV 2016005257A SV 2016005257 A SV2016005257 A SV 2016005257A SV 2016005257 A SV2016005257 A SV 2016005257A SV 2016005257 A SV2016005257 A SV 2016005257A
Authority
SV
El Salvador
Prior art keywords
aminas
benzimidazol
compositions
midh1
inhibitors
Prior art date
Application number
SV2016005257A
Other languages
English (en)
Spanish (es)
Inventor
Hartmut Rehwinkel
Olaf Panknin
Sven Ring
Sonja Anlauf
Holger Siebeneicher
Duy Nguyen
Wolfgang Schwede
Marcus Bauser
Katja Zimmermann
Roland Neuhaus
Paul Matthew Blaney
Stefan Kaulfuss
Original Assignee
Bayer Pharma AG
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
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=52462928&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=SV2016005257(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bayer Pharma AG filed Critical Bayer Pharma AG
Publication of SV2016005257A publication Critical patent/SV2016005257A/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C07D235/30—Nitrogen atoms not forming part of a nitro radical
    • 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
    • A61K31/41—Heterocyclic 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic 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
    • C07D401/02—Heterocyclic 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
    • C07D401/12—Heterocyclic 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Oncology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
SV2016005257A 2014-02-11 2016-08-11 Benzimidazol-2-aminas como inhibidores de midh1 SV2016005257A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP14154680 2014-02-11
EP14182002 2014-08-22

Publications (1)

Publication Number Publication Date
SV2016005257A true SV2016005257A (es) 2018-10-02

Family

ID=52462928

Family Applications (1)

Application Number Title Priority Date Filing Date
SV2016005257A SV2016005257A (es) 2014-02-11 2016-08-11 Benzimidazol-2-aminas como inhibidores de midh1

Country Status (23)

Country Link
US (2) US9957235B2 (OSRAM)
EP (1) EP3105209B1 (OSRAM)
JP (1) JP6534675B2 (OSRAM)
KR (1) KR20160115991A (OSRAM)
CN (1) CN106573897B (OSRAM)
AP (1) AP2016009371A0 (OSRAM)
AU (1) AU2015217788B2 (OSRAM)
BR (1) BR112016018604A2 (OSRAM)
CA (1) CA2939026A1 (OSRAM)
CL (1) CL2016002033A1 (OSRAM)
CR (1) CR20160361A (OSRAM)
CU (1) CU24410B1 (OSRAM)
DO (1) DOP2016000208A (OSRAM)
EA (1) EA031655B1 (OSRAM)
IL (1) IL246785A0 (OSRAM)
MX (1) MX2016010474A (OSRAM)
PE (1) PE20170143A1 (OSRAM)
PH (1) PH12016501581A1 (OSRAM)
SG (1) SG11201605810WA (OSRAM)
SV (1) SV2016005257A (OSRAM)
TW (1) TWI666202B (OSRAM)
UY (1) UY35991A (OSRAM)
WO (1) WO2015121210A1 (OSRAM)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2939021C (en) 2014-02-11 2022-07-12 Bayer Pharma Aktiengesellschaft Benzimidazol-2-amines as midh1 inhibitors
WO2015121210A1 (en) 2014-02-11 2015-08-20 Bayer Pharma Aktiengesellschaft Benzimidazol-2-amines as midh1 inhibitors
SI3447050T1 (sl) 2014-09-19 2020-08-31 Forma Therapeutics, Inc. Derivati piridin-2(1H)-on kinolinona kot inhibitorji mutirane izocitratne dehidrogenaze
CA2961793C (en) 2014-09-19 2021-03-16 Forma Therapeutics, Inc. Quinolinone pyrimidines compositions as mutant-isocitrate dehydrogenase inhibitors
WO2016062770A1 (en) * 2014-10-23 2016-04-28 Bayer Pharma Aktiengesellschaft 1-cyclohexyl-2-phenylaminobenzimidazoles as midh1 inhibitors for the treatment of tumors
JP6783756B2 (ja) * 2014-10-23 2020-11-11 ドイチェス クレープスフォルシュングスツェントルム シュティフトゥング デス エッフェントリッヒェン レヒツ ｍＩＤＨ１阻害剤としてのベンゾイミダゾール−２−アミン
US10370339B2 (en) 2015-06-08 2019-08-06 Bayer Pharma Aktiengesellschaft N-Methylbenzimidazoles as mIDH1 inhibitors
CA2991360A1 (en) * 2015-07-07 2017-01-12 Bayer Pharma Aktiengesellschaft 2-aryl- and 2-arylalkyl-benzimidazoles as midh1 inhibitors
US10414734B2 (en) 2015-07-16 2019-09-17 Bayer Pharma Aktiengesellschaft 5-hydroxyalkylbenzimidazoles as mIDH1 inhibitors
EP3121166A1 (en) 2015-07-21 2017-01-25 Bayer Pharma Aktiengesellschaft Fused imidazoles as midh1 inhibitors
TW201708193A (zh) * 2015-07-27 2017-03-01 拜耳製藥公司 突變之異檸檬酸脫氫酶ｉｄｈ１ ｒ１３２ｈ之抑制劑
TW201718513A (zh) * 2015-07-27 2017-06-01 拜耳製藥公司 製備經取代之３－（２－苯胺－１－環己基－１ｈ－苯并咪唑－５－基）丙酸衍生物之方法
CN109071423A (zh) * 2016-02-09 2018-12-21 益方生物科技（上海）有限公司 吲哚胺-2,3-双加氧酶(ido)抑制剂
WO2019015672A1 (zh) * 2017-07-21 2019-01-24 南京明德新药研发股份有限公司 吡啶并咪唑类化合物及其应用
EP3661559A1 (en) 2017-08-01 2020-06-10 Deutsches Krebsforschungszentrum Stiftung des Öffentlichen Rechts Combination of midh1 inhibitors and dna hypomethylating agents (hma)
US11013733B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mlDH-1)
US10532047B2 (en) 2018-05-16 2020-01-14 Forma Therapeutics, Inc. Solid forms of ((S)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile
US11311527B2 (en) 2018-05-16 2022-04-26 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mIDH-1)
US11013734B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Treating patients harboring an isocitrate dehydrogenase-1 (IDH-1) mutation
US11576906B2 (en) 2018-05-16 2023-02-14 Forma Therapeutics, Inc. Inhibiting mutant IDH-1
JP7258059B2 (ja) * 2018-06-26 2023-04-14 昆薬集団股▲フン▼有限公司 ベンズイミダゾール誘導体及びそのｉｄｈ１阻害剤としての応用
TWI760017B (zh) * 2019-12-23 2022-04-01 大陸商昆藥集團股份有限公司 一種ｉｄｈ１突變體抑制劑的鹽型、晶型及其製備方法
US12014835B2 (en) 2020-02-19 2024-06-18 Vanderbilt University Methods for evaluating therapeutic benefit of combination therapies
WO2022019289A1 (ja) 2020-07-21 2022-01-27 第一三共株式会社 テモゾロミドと変異型ｉｄｈ１酵素阻害剤の組み合わせ医薬
CN112062687B (zh) * 2020-09-02 2023-11-21 上海信谊万象药业股份有限公司 一种盐酸阿扎司琼中间体3-氨基-5-氯-2-羟基苯甲酸甲酯的合成方法

Family Cites Families (35)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2643903A1 (fr) 1989-03-03 1990-09-07 Union Pharma Scient Appl Nouveaux derives de benzimidazole, leurs procedes de preparation, intermediaires de synthese, compositions pharmaceutiques les contenant, utiles notamment pour le traitement des maladies cardiovasculaires, et des ulceres duodenaux
CN1161340C (zh) 1998-11-30 2004-08-11 先灵公司 为玻连蛋白受体拮抗剂的苯并咪唑化合物
US6340681B1 (en) 1999-07-16 2002-01-22 Pfizer Inc 2-benzimidazolylamine compounds as ORL-1-receptor agonists
US6448281B1 (en) 2000-07-06 2002-09-10 Boehringer Ingelheim (Canada) Ltd. Viral polymerase inhibitors
US7030150B2 (en) 2001-05-11 2006-04-18 Trimeris, Inc. Benzimidazole compounds and antiviral uses thereof
CA2448737C (en) 2001-07-20 2010-06-01 Boehringer Ingelheim (Canada) Ltd. Viral polymerase inhibitors
DE60314500T2 (de) 2002-03-01 2008-02-07 Smithkline Beecham Corp. Diaminopyrimidine und deren verwendung als angiogenesehemmer
US7531553B2 (en) 2003-03-21 2009-05-12 Amgen Inc. Heterocyclic compounds and methods of use
WO2005044793A2 (en) 2003-10-31 2005-05-19 Takeda Pharmaceutical Company Limited Nitrogen-containing fused heterocyclic compounds
WO2005121132A1 (ja) 2004-06-11 2005-12-22 Shionogi & Co., Ltd. 抗ｈｃｖ作用を有する縮合ヘテロ環化合物
WO2006038738A1 (ja) 2004-10-08 2006-04-13 Takeda Pharmaceutical Company Limited 受容体機能調節剤
AU2006223070B2 (en) 2005-03-14 2012-02-09 High Point Pharmaceuticals, Llc Benzazole derivatives, compositions, and methods of use as B-secretase inhibitors
WO2008153701A1 (en) * 2007-05-24 2008-12-18 Schering Corporation Compounds for inhibiting ksp kinesin activity
WO2009059214A1 (en) 2007-11-02 2009-05-07 The Regents Of The University Of California Abeta-binding small molecules
WO2009116074A2 (en) 2008-02-13 2009-09-24 Cadila Healthcare Limited Substituted benzimidazoles as cannabinoid modulator
UY32138A (es) 2008-09-25 2010-04-30 Boehringer Ingelheim Int Amidas sustituidas del ácido 2-(2,6-dicloro-fenilamino)-6-fluoro-1-metil-1h-bencimidazol-5-carboxílico y sus sales farmacéuticamente aceptables
UY32470A (es) 2009-03-05 2010-10-29 Boehringer Ingelheim Int Derivados de 2-{2-cloro-5-[(sustituido) metil]fenilamino} -1-metil]fenilamino}-1-metilbencimidazol-5-carboxamidas-n-(sustituidas) y sus sales fisiológicamente aceptables, composiciones conteniéndolos y aplicaciones
US9125901B2 (en) * 2009-06-23 2015-09-08 The Translational Genomics Research Institute 4-(benzimidazol-2-ylamino)benzamide derivatives and salts or solvates thereof
JP5967827B2 (ja) 2009-12-09 2016-08-10 アジオス ファーマシューティカルズ， インコーポレイテッド Ｉｄｈ変異体をもつことを特徴とする癌治療用の治療的活性化合物
WO2012172043A1 (en) * 2011-06-15 2012-12-20 Laboratoire Biodim Purine derivatives and their use as pharmaceuticals for prevention or treatment of bacterial infections
CN102827170A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN103435554A (zh) 2013-09-06 2013-12-11 中国药科大学 2-苯氨基苯并咪唑类化合物及其用途
WO2015121210A1 (en) 2014-02-11 2015-08-20 Bayer Pharma Aktiengesellschaft Benzimidazol-2-amines as midh1 inhibitors
CA2939021C (en) 2014-02-11 2022-07-12 Bayer Pharma Aktiengesellschaft Benzimidazol-2-amines as midh1 inhibitors
WO2016062770A1 (en) 2014-10-23 2016-04-28 Bayer Pharma Aktiengesellschaft 1-cyclohexyl-2-phenylaminobenzimidazoles as midh1 inhibitors for the treatment of tumors
JP6783756B2 (ja) 2014-10-23 2020-11-11 ドイチェス クレープスフォルシュングスツェントルム シュティフトゥング デス エッフェントリッヒェン レヒツ ｍＩＤＨ１阻害剤としてのベンゾイミダゾール−２−アミン
JP2018515623A (ja) 2015-05-18 2018-06-14 トランスレイショナル・ドラッグ・ディベロップメント・エルエルシー キナーゼ阻害剤としての複素環式化合物
AU2016267059B2 (en) 2015-05-22 2020-08-13 Translational Drug Development Llc Benzamide and active compound compositions and methods of use
US10370339B2 (en) 2015-06-08 2019-08-06 Bayer Pharma Aktiengesellschaft N-Methylbenzimidazoles as mIDH1 inhibitors
CA2991360A1 (en) 2015-07-07 2017-01-12 Bayer Pharma Aktiengesellschaft 2-aryl- and 2-arylalkyl-benzimidazoles as midh1 inhibitors
US10414734B2 (en) 2015-07-16 2019-09-17 Bayer Pharma Aktiengesellschaft 5-hydroxyalkylbenzimidazoles as mIDH1 inhibitors
EP3121166A1 (en) 2015-07-21 2017-01-25 Bayer Pharma Aktiengesellschaft Fused imidazoles as midh1 inhibitors
TW201708193A (zh) 2015-07-27 2017-03-01 拜耳製藥公司 突變之異檸檬酸脫氫酶ｉｄｈ１ ｒ１３２ｈ之抑制劑
TW201718513A (zh) 2015-07-27 2017-06-01 拜耳製藥公司 製備經取代之３－（２－苯胺－１－環己基－１ｈ－苯并咪唑－５－基）丙酸衍生物之方法
EP3423439A4 (en) 2016-03-02 2019-08-14 Translational Drug Development Llc aminobenzimidazole derivatives

Also Published As

Publication number Publication date
SG11201605810WA (en) 2016-08-30
EP3105209A1 (en) 2016-12-21
US20190062285A1 (en) 2019-02-28
US20170197921A1 (en) 2017-07-13
US9957235B2 (en) 2018-05-01
EP3105209B1 (en) 2019-08-21
CL2016002033A1 (es) 2017-03-31
AU2015217788A1 (en) 2016-08-04
MX2016010474A (es) 2016-10-31
CN106573897A (zh) 2017-04-19
EA201691590A1 (ru) 2017-02-28
BR112016018604A2 (pt) 2017-08-08
TWI666202B (zh) 2019-07-21
TW201613874A (en) 2016-04-16
AU2015217788B2 (en) 2019-06-27
WO2015121210A1 (en) 2015-08-20
PE20170143A1 (es) 2017-03-19
JP6534675B2 (ja) 2019-06-26
PH12016501581A1 (en) 2017-02-06
US10442772B2 (en) 2019-10-15
KR20160115991A (ko) 2016-10-06
CU24410B1 (es) 2019-05-03
DOP2016000208A (es) 2016-09-15
CU20160120A7 (es) 2016-12-23
UY35991A (es) 2015-09-30
CR20160361A (es) 2016-10-03
IL246785A0 (en) 2016-08-31
EA031655B1 (ru) 2019-02-28
JP2017505790A (ja) 2017-02-23
AP2016009371A0 (en) 2016-08-31
CA2939026A1 (en) 2015-08-20
CN106573897B (zh) 2019-09-24

Similar Documents

Publication Publication Date Title
SV2016005257A (es) Benzimidazol-2-aminas como inhibidores de midh1
CY1124855T1 (el) 2-(μορφολιν-4-υλ)-1,7-ναφθυριδινες
CL2017003404A1 (es) Compuestos antibacterianos
MX2022012313A (es) Oxisteroles y metodos de uso de los mismos.
CR20160337A (es) Nuevas heteroarildihidropirimidinas 6-fusionadas para el tratamiento y la profilaxis de la infección por virus de la hepatitis b
DOP2015000274A (es) Compuestos químicos
MX386935B (es) Profármacos de fumaratos y su uso en el tratamiento de diferentes enfermedades.
CR20160241A (es) Nuevas dihidroquinolizinonas para el tratamiento y profilaxis de la infección por virus de la hepatitis b
CR20170573A (es) Lactamas bicíclicas y métodos de uso de las mismas
UY35898A (es) ?compuestos inhibidores de syk y composiciones que los comprenden?.
MX2016014547A (es) Compuestos para tratar atrofia muscular espinal.
NI201600018A (es) Derivados de pirrolamida sustituidos con glioxamida y su uso como medicamentos para el tratamiento de la hepatitis b.
MX2020011104A (es) Composiciones farmaceuticas de compuestos terapeuticamente activos y sus metodos de uso.
DOP2016000173A (es) Heteroarilos y usos de estos
MX2017004541A (es) Derivados espirodiamina como inhibidores de la aldosterona sintasa.
SV2017005405A (es) Compuestos y composiciones como inhibidores de quinasa raf
ECSP16074478A (es) Compuestos novedosos
UY35293A (es) Isotiazoles sustituidos con amino
CR20160433A (es) Nuevos compuestos
DOP2017000107A (es) Diamino-quinoleina 2,4 sustituida como nuevos agentes anticancerigenos
UY37250A (es) Derivados macrocíclicos de indol
DOP2020000100A (es) Novedosos derivados de pirazolo-pirrolo-pirimidina como inhibidores de p2x3
DOP2017000146A (es) Pirazolpiridinaminas como inhibidores de mknk1 y mknk2
CR20160316A (es) Compuestos derivados de hidroxiformamida y usos del mismo
SV2016005293A (es) Compuestos de azol amido-sustituidos como inhibidores de tnks1 y/o tnks2