CO5190710A1 - ANTAGONISTS OF AN IL-8 RECEIVER AN IL-8 RECEIVER - Google Patents

ANTAGONISTS OF AN IL-8 RECEIVER AN IL-8 RECEIVER

Info

Publication number
CO5190710A1
CO5190710A1 CO00044233A CO00044233A CO5190710A1 CO 5190710 A1 CO5190710 A1 CO 5190710A1 CO 00044233 A CO00044233 A CO 00044233A CO 00044233 A CO00044233 A CO 00044233A CO 5190710 A1 CO5190710 A1 CO 5190710A1
Authority
CO
Colombia
Prior art keywords
alkyl
cr8r8
alkenyl
optionally substituted
heteroaryl
Prior art date
Application number
CO00044233A
Other languages
Spanish (es)
Inventor
Gregory M Benson
Original Assignee
Smithkline Beecham Corp
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 Smithkline Beecham Corp filed Critical Smithkline Beecham Corp
Publication of CO5190710A1 publication Critical patent/CO5190710A1/en

Links

Classifications

    • 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
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
    • 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
    • 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
    • A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
    • 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
    • A61K31/4406—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 3, e.g. zimeldine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • 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
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compuesto para tratar un estado de enfermedad mediado por quimioquina, seleccionado del grupo que consta de malaria, reestenosis, angiogénesis, aterosclerosis, osteoporosis, gingivitis, liberación de células tronco hematopoyéticas indeseadas, y enfermedades causadas por virus respiratorios, virus del herpes, y virus de la hepatitis, en el que la quimioquina se fija a un receptor de IL-8 a ó ß en un mamífero, dicho compuesto de fórmula:<EMI FILE="00044233_1" ID="1" IMF=JPEG >en la queX es oxígeno o azufre;R es cualquier resto funcional que tiene un hidrógeno ionizable y un pKa de 10 o menos;R1 se selecciona independientemente entre hidrógeno, halógeno, nitro, ciano, alquilo C1-10 sustituido con halo, alquilo C1-10, alquenilo C2-10, alcoxi C1-10, alcoxi C1-10 halosustituido, azido, (CR8R8)qS(O)tR4, hidroxi, hidroxi-alquilo C1-4, arilo, aril-alquilo C1-4, ariloxi, aril-alquil C1-4-oxi, heteroarilo, heteroaril-alquilo, heterocíclico, heterocíclico-alquilo C1-4, heteroaril-alquil C1-4-oxi, aril-alquenilo C2-10, heteroaril-alquenilo C2-10, heterocíclico-alquenilo C2-10, (CR8R8)qNR4R5 alquenil C2-10-C(O)-NR4R5, (CR8R8)qC(O)NR4R5, (CR8R8)qC(O)NR4R10, S(O)3H, S(O)3R8, (CR8R8)qC(O)R11, alquenil C2-10-C(O)R11, alquenil C2-10-C(O)OR11 (CR8R8)qC(O)OR12, (CR8R8)qOC(O)R11, (CR8R8)qNR4C(O)R11, (CR8R8)q-NHS(O)2R17, (CR8R8)qS(O)2NR4R5, o dos restos R1 juntos pueden formar O-(CH2)S-O- o un anillo insaturado de 5 a 6 miembros;q es 0, o un número entero que tiene un valor de 1 a 10;m es un número entero que tiene un valor de 1 a 3;t es 0, o un número entero que tiene un valor de 1 ó 2;s es un número entero que tiene un valor de 1 a 3;v es 0, o un número entero que tiene un valor de 1 a 4;R4 y R5 son independientemente hidrógeno, alquilo C1-4opcionalmente sustituido, arilo opcionalmente sustituido, aril-alquilo C1-4 opcionalmente sustituido,heteroarilo opcionalmente sustituido, heteroaril-alquilo C1-4 opcionalmente sustituido, heterocíclico o heterocíclico-alquilo C1-4, o R4 y R5 junto con el nitrógeno al que están unidos, forman un anillo de 5 a 7 miembros que opcionalmente puede comprender un heteroátomo adicional seleccionado entre oxígeno, nitrógeno y azufre;HET es un resto heteroarilo opcionalmente sustituido;R8 es hidrógeno o alquilo C1-4;R10 es alquil C1-10-C(O)2R8; ...Compound to treat a chemokine-mediated disease state, selected from the group consisting of malaria, restenosis, angiogenesis, atherosclerosis, osteoporosis, gingivitis, release of unwanted hematopoietic stem cells, and diseases caused by respiratory viruses, herpes viruses, and Hepatitis, in which the chemokine is fixed to an IL-8 a or β receptor in a mammal, said compound of the formula: <EMI FILE = "00044233_1" ID = "1" MFI = JPEG> where X is oxygen or sulfur; R is any functional moiety having an ionizable hydrogen and a pKa of 10 or less; R1 is independently selected from hydrogen, halogen, nitro, cyano, halo substituted C1-10 alkyl, C1-10 alkyl, C2 alkenyl 10, C1-10 alkoxy, halosubstituted C1-10 alkoxy, azido, (CR8R8) qS (O) tR4, hydroxy, hydroxyC 1-4 alkyl, aryl, arylC 1-4 alkyl, aryloxy, arylC 1-4 alkyl -oxy, heteroaryl, heteroaryl-alkyl, heterocyclic, heterocyclic-C1-4alkyl, heteroaryl-alk C1-4-oxy, C2-10 aryl-alkenyl, C2-10 heteroaryl-alkenyl, C2-10 heterocyclic-alkenyl, (CR8R8) qNR4R5 C2-10-C (O) -NR4R5, (CR8R8) qC (O ) NR4R5, (CR8R8) qC (O) NR4R10, S (O) 3H, S (O) 3R8, (CR8R8) qC (O) R11, C2-10-C alkenyl (O) R11, C2-10-C alkenyl (O) OR11 (CR8R8) qC (O) OR12, (CR8R8) qOC (O) R11, (CR8R8) qNR4C (O) R11, (CR8R8) q-NHS (O) 2R17, (CR8R8) qS (O) 2NR4R5 , or two R1 moieties together can form O- (CH2) SO- or an unsaturated ring of 5 to 6 members; q is 0, or an integer having a value of 1 to 10; m is an integer that has a value from 1 to 3; t is 0, or an integer that has a value of 1 or 2; s is an integer that has a value of 1 to 3; v is 0, or an integer that has a value of 1 to 4; R4 and R5 are independently hydrogen, optionally substituted C1-4 alkyl, optionally substituted aryl, optionally substituted aryl-C1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl-C1-4 alkyl, heterocyclic or heterocyclic-alkyl C1-4, or R4 and R5 together with the nitrogen to which they are attached, form a 5- to 7-membered ring that may optionally comprise an additional heteroatom selected from oxygen, nitrogen and sulfur; HET is an optionally substituted heteroaryl moiety; R8 is hydrogen or C1-4 alkyl; R10 is C1-10-C (O) 2R8 alkyl; ...

CO00044233A 1999-06-15 2000-06-14 ANTAGONISTS OF AN IL-8 RECEIVER AN IL-8 RECEIVER CO5190710A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US13968099P 1999-06-15 1999-06-15

Publications (1)

Publication Number Publication Date
CO5190710A1 true CO5190710A1 (en) 2002-08-29

Family

ID=22487818

Family Applications (1)

Application Number Title Priority Date Filing Date
CO00044233A CO5190710A1 (en) 1999-06-15 2000-06-14 ANTAGONISTS OF AN IL-8 RECEIVER AN IL-8 RECEIVER

Country Status (6)

Country Link
EP (1) EP1194143A4 (en)
JP (1) JP2003501450A (en)
AU (1) AU6051200A (en)
CO (1) CO5190710A1 (en)
HK (1) HK1044717A1 (en)
WO (1) WO2000076457A2 (en)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1608319A4 (en) 2003-04-03 2007-02-28 Univ California Improved inhibitors for the soluble epoxide hydrolase
EP1765311A4 (en) 2004-03-16 2009-04-29 Univ California Reducing nephropathy with inhibitors of soluble epoxide hydrolase and epoxyeicosanoids
AU2005295167B2 (en) 2004-10-20 2012-05-10 The Regents Of The University Of California Improved inhibitors for the soluble epoxide hydrolase
AR059826A1 (en) 2006-03-13 2008-04-30 Univ California UREA INHIBITORS CONFORMATIONALLY RESTRICTED OF SOLUBLE HYDROLASSE EPOXIDE
EP2528604B1 (en) 2010-01-29 2017-11-22 The Regents of the University of California Acyl piperidine inhibitors of soluble epoxide hydrolase

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4008326A (en) * 1973-12-26 1977-02-15 The Upjohn Company Substituted ureas and thioureas and pharmaceutical compositions thereof
EP0809492A4 (en) * 1995-02-17 2007-01-24 Smithkline Beecham Corp Il-8 receptor antagonists
JP2000513359A (en) * 1996-06-27 2000-10-10 スミスクライン・ビーチャム・コーポレイション IL-8 receptor antagonist

Also Published As

Publication number Publication date
EP1194143A2 (en) 2002-04-10
WO2000076457A2 (en) 2000-12-21
WO2000076457A3 (en) 2001-05-17
AU6051200A (en) 2001-01-02
JP2003501450A (en) 2003-01-14
EP1194143A4 (en) 2004-02-04
HK1044717A1 (en) 2002-11-01

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