[go: up one dir, main page]

AR033617A1 - Compuestos derivados espirociclicos, metodos para prepararlos y su uso como inhibidores de fosfodiesterasa-7 - Google Patents

Compuestos derivados espirociclicos, metodos para prepararlos y su uso como inhibidores de fosfodiesterasa-7

Info

Publication number
AR033617A1
AR033617A1 ARP020100993A ARP020100993A AR033617A1 AR 033617 A1 AR033617 A1 AR 033617A1 AR P020100993 A ARP020100993 A AR P020100993A AR P020100993 A ARP020100993 A AR P020100993A AR 033617 A1 AR033617 A1 AR 033617A1
Authority
AR
Argentina
Prior art keywords
lower alkyl
substituted
heteroatoms
hydrogen
optionally interrupted
Prior art date
Application number
ARP020100993A
Other languages
English (en)
Inventor
Patrick Bernardellli
Pierre Ducrot
Fabrice Vergne
Edwige Lorthiois
Original Assignee
Warner Lambert Co
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=8164349&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=AR033617(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Warner Lambert Co filed Critical Warner Lambert Co
Publication of AR033617A1 publication Critical patent/AR033617A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
    • C07D239/80—Oxygen atoms
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • 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
    • 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
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • 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
    • 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
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/04—Immunostimulants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic agents
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic 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
    • C07D413/12—Heterocyclic 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 linked by a chain containing hetero atoms as chain links

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Pulmonology (AREA)
  • Oncology (AREA)
  • Virology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Communicable Diseases (AREA)
  • Pain & Pain Management (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Molecular Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

Compuestos de formulas (1), (2) o (3) donde: a) X1, X2, X3 y X4 son -N, siempre que no más de dos de ellos sean nitrogeno, o -C-R1; R1 es Q1, alquilo, alquenilo o alquinilo inferiores, no sustituidos o sustituidos con uno o varios grupos Q2; X5-R5, X5 es un solo enlace, alquileno, alquenileno o alquinileno inferiores, optativamente interrumpido con 1 o 2 heteroátomos de O, S, S(=O), SO2 o N, los carbonos de estos grupos son no sustituidos o sustituidos con uno o varios grupos, de SR6, OR6, NR6R7, =O, =S, o =N-R6, R6 y R7 son hidrogeno o alquilo inferiores, R5 es arilo, heteroarilo, cicloalquilo optativamente interrumpido con C(=O) o con 1, 2 o 3 heteroátomos de O, S, S(=O), SO2 o N, cicloalquenilo optativamente interrumpido con C(=O) o con 1, 2 o 3 heteroátomos de O, S, S(=O), SO2 o N, o un grupo bicíclico no sustituidos o sustituidos con uno o varios grupos de Q3, heteroarilo o alquilo inferiores optativamente sustituidos con Q3; Q1, Q2 Q3 son hidrogeno, halogeno, CN, NO2, SO3H, P(=O)(OH)2, OR2, OC(=O)R2, C(=O)OR2, SR2, S(=O)R2, C(=O)-NH-SO2-CH3, NR3R4, Q-R2, Q-NR3R4, NR2-Q-NR3R4 o NR3-Q-R2; Q es C(=NR), C(=O), C(=S) o SO2; R es hidrogeno, CN o SO2NH2 o alquilo inferior y R2, R3 y R4 son hidrogeno, alquilo inferior optativamente interrumpido con C(=O), Q4-arilo, Q4-heteroarilo, Q4-cicloalquilo optativamente interrumpido con C(=O) o con 1 o 2 heteroátomos de O, S, S(=O), SO2 o N, o Q4-cicloalquenilo optativamente interrumpido con C(=O) o con 1 o 2 heteroátomos de O, S, S(=O), SO2 o N; Q4 es (CH2)n, alquilo inferior con un heteroátomo de O, S o N, alquenilo o alquinilo inferiores, optativamente sustituidos con alquilo inferior, OR', o NR'R''; R' y R'' son hidrogeno o alquilo inferior; n es un numero entero de 0, 1, 2, 3 o 4; estos grupos son no sustituidos o sustituidos con uno o varios grupos halogeno, CN, CH3, SO3H, SO2CH3, C(=O)-NH-SO2-CH3, CF3, OR6, COOR6, C(=O)R6, NR6R7, NR6C(=O)R7, C(=O)NR6R7 o SO2NR6R7, en donde R6 y R7 son hidrogeno o alquilo inferior optativamente sustituido con uno o dos grupos de OR, COOR, o NRR8; R y R8 son hidrogeno o alquilo inferior y R6 y R7, y/o, R3 y R4, junto con el átomo de nitrogeno al cual están unidos, pueden formar un anillo heterocíclico de 4 a 8 miembros, con uno o dos heteroátomos de O, S, S(=O), SO2 o N, y que puede ser sustituido con (CH2)n-Q5, n es un numero entero de 0, 1, 2 o 3 y Q5 es un anillo heterocíclico de 4 a 8 miembros, con uno o dos heteroátomos de O, S o N y que puede ser sustituido con un alquilo o un alquilo inferior optativamente sustituido con OR', NR'R'', C(=O)NR'R'' o COOR'; R' y R'' son H o alquilo inferior optativamente sustituido con OR o COOR donde R es hidrogeno o alquilo inferior y R' y R'' junto con el átomo de nitrogeno al cual están unidos, pueden formar un anillo heterocíclico de 4 a 8 miembros, con uno o dos heteroátomos seleccionados de O, S o N; o cuando X1 y X2 ambos representan C-R1, los dos sustituyentes R1 pueden formar junto con los átomos de carbono a los cuales están unidos, un anillo heterocíclico de 5 miembros que comprende un átomo de nitrogeno y optativamente un segundo heteroátomo de O, S o N; b) X es O o NR9, donde R9 es hidrogeno, CN, OH, NH2, alquilo, alquenilo o alquinilo inferiores, no sustituidos o sustituidos con cicloalquilo optativamente interrumpido con 1 o 2 heteroátomos de O, S, S(=O), SO2 o N, cicloalquenilo optativamente interrumpido con 1 o 2 heteroátomos elegidos de O, S, S(=O), SO2 o N, arilo, heteroarilo, OR10, COOR10 o NR10R11, donde R10 y R11 son hidrogeno o alquilo inferior; c) Y es O, S o N-R12; R12 es hidrogeno, CN, OH, NH2, alquilo, alquenilo o alquinilo inferiores, no sustituidos o sustituidos con cicloalquilo optativamente interrumpido con 1 o 2 heteroátomos de O, S, S(=O), SO2 o N, cicloalquenilo optativamente interrumpido con 1 o 2 heteroátomos elegidos de O, S, S(=O), SO2 o N, arilo, heteroarilo, OR10, COOR10 o NR10R11, donde R10 y R11 son hidrogeno o alquilo inferior; d) Z es CH-NO2, O, S o NR13, donde R13 es hidrogeno, CN, OH, NH2, arilo, heteroarilo, cicloalquilo optativamente interrumpido con uno o varios heteroátomos de O, S, S(=O), SO2 o N, cicloalquenilo optativamente interrumpido con uno o varios heteroátomos de O, S, S(=O), SO2 o N, C(=O)R14, C(=O)NR14R15, OR14, o alquilo inferior, no sustituido o sustituido con uno o varios grupos que son OR14, COOR10, o NR14R15; R14 y R15 son hidrogeno o alquilo inferior, o, R14 y R15, junto con el átomo de nitrogeno al cual están unidos, pueden formar un anillo heterocíclico de 4 a 8 miembros con uno o dos heteroátomos de O, S o N, sustituido con un alquilo inferior o cuando Y es N-R12 y Z es N-R13, pueden formar juntos grupos -CH=N- o -C=C-, cuando X es N-R9 y Z es N-R13, R9 y R13 pueden formar juntos un grupo -CH=N- o un grupo -C=C-; e) Z1 es H, CH3 o NR16R17, R16 y R17 son hidrogeno, CN, arilo, heteroarilo, cicloalquilo optativamente interrumpido con uno o varios heteroátomos de O, S, S(=O), SO2 o N, cicloalquenilo optativamente interrumpido con uno o varios heteroátomos de O, S, S(=O), SO2 o N, C(=O)R14, C(=O)NR14R15, OR14, o alquilo inferior no sustituido o sustituido con uno o varios grupos de OR14, COOR14 o NR14R15; R14 y R15 son hidrogeno o alquilo inferior y R14 y R15, y/o, R16 y R17, junto con el átomo de nitrogeno al cual están unidos, pueden formar un anillo heterocíclico de 4 a 8 miembros con uno o más heteroátomos de O, S o N, sustituido con un alquilo inferior; f) A es un ciclo elegido del grupo (4), donde A1, A2, A4, A5 y A6 son O, S, C, C(=O), SO, SO2 o N-R18 y R18 es hidrogeno, arilo, heteroarilo, cicloalquilo optativamente interrumpidos con uno o varios heteroátomos de O, S, S(=O), SO2 o N, cicloalquenilo optativamente interrumpido con uno o varios heteroátomos de O, S, S(=O), SO2 o N, alquilo inferior no sustituido o sustituido con arilo, heteroarilo, cicloalquilo optativamente interrumpido con uno o varios heteroátomos de O, S, S(=O), SO2 o N, cicloalquenilo optativamente interrumpido con uno o varios heteroátomos de O, S, S(=O), SO2 o N, CN, NR19R20, C(=O)NR19R20, OR19, C(=O)R19 o C(=O)OR19 en donde R19 y R20 son hidrogeno o alquilo inferior; A3 es O, S, C, C(=O), SO, SO2 o N-R18 cuando A1 y/o A2 son C(=O) o cuando Y es O o S, R18 es lo definido anteriormente; * representa un átomo de carbono que se comparte entre el ciclo A y el ciclo de la cadena principal que contiene X y/o Y; cada carbono del ciclo A es no sustituido o sustituido con 1 o 2 grupos alquilo inferior optativamente sustituido con OR21, NR21R22, COOR21 o CONR21R22, haloalquilo inferior, CN, F, =O, SO2NR19R20, OR19, SR19, C(=O)OR19, C(=O)NR19R20 o NR19R20, donde R19 y R20 son hidrogeno o alquilo inferior optativamente sustituido con OR21, NR21R22, COOR21 o CONR21R22 en donde R21 y R22 son hidrogeno o alquilo inferior, y R19 y R20, y/o, R21 y R22, junto con el átomo de nitrogeno al cual están unidos, pueden formar un anillo heterocíclico de 4 a 8 miembros; 2 átomos del ciclo A, que no son adyacentes, pueden ser unidos por una cadena de 2, 3 o 4 átomos de carbono que puede ser interrumpida con 1 heteroátomo de O, S o N; siempre que no más de dos de los grupos A1, A2, A3, A4, A5 y A6 simultáneamente sean un heteroátomo; el ciclo A no contenga más de 2 carbonos en un estado de hibridacion sp2; cuando X es O, X2 no es C-R1, R1 es un tienilo sustituido con CN o con CN y CH3, un fenilo sustituido con CN, Cl, NO2 o CN y F, Br, F o sus tautomeros, racémicos o isomeros y sus derivados farmacéuticamente aceptables. Se usan en composiciones farmacéuticas como inhibidor de PDE7, para prevencion o tratamiento de enfermedades relacionadas con células T, enfermedades autoinmunes, osteoartritis, esclerosis multiple, enfermedad pulmonar obstructiva cronica, asma, cáncer, síndrome de inmunodeficiencia adquirida, alergia o enfermedad intestinal inflamatoria. Método para preparar los compuestos de formula (1) haciendo reaccionar una urea sustituida con una cetona cíclica.
ARP020100993A 2001-03-21 2002-03-20 Compuestos derivados espirociclicos, metodos para prepararlos y su uso como inhibidores de fosfodiesterasa-7 AR033617A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/EP2001/003355 WO2002076953A1 (en) 2001-03-21 2001-03-21 New spirotricyclic derivatives and their use as phosphodiesterase-7 inhibitors

Publications (1)

Publication Number Publication Date
AR033617A1 true AR033617A1 (es) 2003-12-26

Family

ID=8164349

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP020100993A AR033617A1 (es) 2001-03-21 2002-03-20 Compuestos derivados espirociclicos, metodos para prepararlos y su uso como inhibidores de fosfodiesterasa-7

Country Status (46)

Country Link
US (3) US20020198198A1 (es)
EP (2) EP1801106A3 (es)
JP (1) JP4086663B2 (es)
KR (1) KR100617435B1 (es)
CN (1) CN100447136C (es)
AP (1) AP1699A (es)
AR (1) AR033617A1 (es)
AT (1) ATE367381T1 (es)
AU (1) AU2002304800B2 (es)
BG (1) BG108181A (es)
BR (1) BR0208192A (es)
CA (1) CA2441313C (es)
CU (1) CU23218A3 (es)
CY (1) CY1106829T1 (es)
CZ (1) CZ20032451A3 (es)
DE (1) DE60221233T2 (es)
DK (1) DK1373224T3 (es)
EA (1) EA006815B1 (es)
EC (1) ECSP034750A (es)
EE (1) EE200300459A (es)
ES (1) ES2288552T3 (es)
GE (1) GEP20053631B (es)
GT (1) GT200200053A (es)
HR (1) HRP20030740A2 (es)
HU (1) HUP0303637A3 (es)
IL (2) IL157659A0 (es)
IS (1) IS2529B (es)
MA (1) MA27001A1 (es)
MX (1) MXPA03008485A (es)
MY (1) MY142045A (es)
NO (1) NO326086B1 (es)
NZ (1) NZ527847A (es)
OA (1) OA12454A (es)
PA (1) PA8541601A1 (es)
PE (1) PE20021010A1 (es)
PL (1) PL367058A1 (es)
PT (1) PT1373224E (es)
RS (1) RS50429B (es)
SI (1) SI1373224T1 (es)
SK (1) SK11562003A3 (es)
SV (1) SV2003000925A (es)
TN (1) TNSN03076A1 (es)
TW (1) TWI267509B (es)
UA (1) UA74243C2 (es)
WO (2) WO2002076953A1 (es)
ZA (1) ZA200306601B (es)

Families Citing this family (56)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1400244A1 (en) 2002-09-17 2004-03-24 Warner-Lambert Company LLC New spirocondensed quinazolinones and their use as phosphodiesterase inhibitors
GB0230195D0 (en) * 2002-12-24 2003-02-05 Biofocus Plc Compound Libraries
HRP20160180T1 (hr) 2003-04-24 2016-03-25 Incyte Holdings Corp Derivati aza spiro alkana kao inhibitori metaloproteaza
JP2006219374A (ja) 2003-06-13 2006-08-24 Daiichi Asubio Pharma Co Ltd Ｐｄｅ７阻害作用を有するイミダゾトリアジノン誘導体
JP2006219373A (ja) 2003-06-13 2006-08-24 Daiichi Asubio Pharma Co Ltd Ｐｄｅ７阻害作用を有するピリジニルピラゾロピリミジノン誘導体
EP1656145A1 (en) * 2003-08-12 2006-05-17 F. Hoffmann-La Roche Ag Spiro-substituted tetrahydroquinazolines as corticotropin releasing factor (cfr) antagonists
CA2569530C (en) 2004-07-01 2013-07-30 Daiichi Asubio Pharma Co.,Ltd. Thienopyrazole derivative having pde 7 inhibitory activity
BRPI0607402A2 (pt) * 2005-03-01 2009-09-01 Pfizer Ltd uso de inibidores de pde7 para o tratamento de dor neuropática
GB0504209D0 (en) * 2005-03-01 2005-04-06 Pfizer Ltd New use of PDE7 inhibitors
WO2006092692A1 (en) * 2005-03-01 2006-09-08 Pfizer Limited Use of combinations of pde7 inhibitors and alpha-2-delty ligands for the treatment of neuropathic pain
KR100680497B1 (ko) * 2005-07-25 2007-02-08 엘지전자 주식회사 근거리통신 시스템에서 단말기가 액세스 포인트에 접속하는방법
EP1928437A2 (en) 2005-08-26 2008-06-11 Braincells, Inc. Neurogenesis by muscarinic receptor modulation
EP2258359A3 (en) 2005-08-26 2011-04-06 Braincells, Inc. Neurogenesis by muscarinic receptor modulation with sabcomelin
JP2009512711A (ja) 2005-10-21 2009-03-26 ブレインセルス，インコーポレイティド Ｐｄｅ阻害による神経新生の調節
WO2007053596A1 (en) 2005-10-31 2007-05-10 Braincells, Inc. Gaba receptor mediated modulation of neurogenesis
EP2218442A1 (en) 2005-11-09 2010-08-18 CombinatoRx, Inc. Methods, compositions, and kits for the treatment of ophthalmic disorders
BRPI0619126A2 (pt) 2005-12-02 2011-09-13 Pfizer Ltd derivados espirocìclicos, composição farmacêutica e usos dos mesmos
US20100216734A1 (en) 2006-03-08 2010-08-26 Braincells, Inc. Modulation of neurogenesis by nootropic agents
EP2026813A2 (en) 2006-05-09 2009-02-25 Braincells, Inc. 5 ht receptor mediated neurogenesis
WO2007134136A2 (en) 2006-05-09 2007-11-22 Braincells, Inc. Neurogenesis by modulating angiotensin
WO2008030651A1 (en) * 2006-09-08 2008-03-13 Braincells, Inc. Combinations containing a 4-acylaminopyridine derivative
US20100184806A1 (en) 2006-09-19 2010-07-22 Braincells, Inc. Modulation of neurogenesis by ppar agents
US8637528B2 (en) 2007-03-27 2014-01-28 Omeros Corporation Use of PDE7 inhibitors for the treatment of movement disorders
MX2009010450A (es) 2007-03-27 2009-11-23 Omeros Corp El uso de inhibidores de la fosfodiesterasa 7 para el tratamiento transtornos del movimiento.
US20100216823A1 (en) * 2007-05-24 2010-08-26 Pfizer Inc. Spirocyclic Derivatives
WO2010099217A1 (en) 2009-02-25 2010-09-02 Braincells, Inc. Modulation of neurogenesis using d-cycloserine combinations
US9220715B2 (en) 2010-11-08 2015-12-29 Omeros Corporation Treatment of addiction and impulse-control disorders using PDE7 inhibitors
JP2014504271A (ja) 2010-11-08 2014-02-20 オメロス コーポレーション Ｐｄｅ７インヒビターを用いる嗜癖および衝動制御障害の処置
US8754114B2 (en) 2010-12-22 2014-06-17 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
EP2804603A1 (en) 2012-01-10 2014-11-26 President and Fellows of Harvard College Beta-cell replication promoting compounds and methods of their use
CN107652289B (zh) 2012-06-13 2020-07-21 因塞特控股公司 作为fgfr抑制剂的取代的三环化合物
US9388185B2 (en) 2012-08-10 2016-07-12 Incyte Holdings Corporation Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors
US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
KR102269032B1 (ko) 2013-04-19 2021-06-24 인사이트 홀딩스 코포레이션 Fgfr 저해제로서 이환식 헤테로사이클
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
PE20171514A1 (es) 2015-02-20 2017-10-20 Incyte Corp Heterociclos biciclicos como inhibidores de fgfr
WO2016134294A1 (en) 2015-02-20 2016-08-25 Incyte Corporation Bicyclic heterocycles as fgfr4 inhibitors
MA41551A (fr) 2015-02-20 2017-12-26 Incyte Corp Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
EP3395817B1 (en) * 2015-12-16 2022-02-23 Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Pyrido[1,2-a]pyrimidone analog, crystal form thereof, intermediate thereof and preparation method therefor
AR111960A1 (es) 2017-05-26 2019-09-04 Incyte Corp Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
CN107382976A (zh) * 2017-07-04 2017-11-24 孙秀芹 一种治疗盆腔炎的化合物及制备方法和应用
AU2018300091B2 (en) * 2017-07-12 2023-06-22 Dart Neuroscience, Llc Substituted benzoxazole and benzofuran compounds as PDE7 inhibitors
BR112020022373A2 (pt) 2018-05-04 2021-02-02 Incyte Corporation sais de um inibidor de fgfr
SG11202010636VA (en) 2018-05-04 2020-11-27 Incyte Corp Solid forms of an fgfr inhibitor and processes for preparing the same
WO2020185532A1 (en) 2019-03-08 2020-09-17 Incyte Corporation Methods of treating cancer with an fgfr inhibitor
WO2021007269A1 (en) 2019-07-09 2021-01-14 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
WO2021067374A1 (en) 2019-10-01 2021-04-08 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
WO2021076602A1 (en) 2019-10-14 2021-04-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
WO2021076728A1 (en) 2019-10-16 2021-04-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
CN115151539A (zh) 2019-12-04 2022-10-04 因赛特公司 Fgfr抑制剂的衍生物
JP7720840B2 (ja) 2019-12-04 2025-08-08 インサイト・コーポレイション Ｆｇｆｒ阻害剤としての三環式複素環
WO2021146424A1 (en) 2020-01-15 2021-07-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
US12065494B2 (en) 2021-04-12 2024-08-20 Incyte Corporation Combination therapy comprising an FGFR inhibitor and a Nectin-4 targeting agent
CA3220155A1 (en) 2021-06-09 2022-12-15 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
AR126102A1 (es) 2021-06-09 2023-09-13 Incyte Corp Heterociclos tricíclicos como inhibidores de fgfr
CN119894518A (zh) 2022-08-18 2025-04-25 米托迪治愈有限责任公司 取代的苯并噁唑和苯并呋喃化合物用于治疗和预防与慢性疲劳、筋疲力尽和/或劳累不耐受相关的疾病的用途

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5815979A (ja) 1981-07-11 1983-01-29 Kyowa Hakko Kogyo Co Ltd 新規なピペリジン誘導体およびその製造法
US4764512A (en) 1986-08-27 1988-08-16 Rorer Pharmaceutical Corporation Benzodiazinone-pyridone compounds, cardiotonic compositions including the same, and their uses
GR1000821B (el) * 1988-11-22 1993-01-25 Tanabe Seiyaku Co Μεθοδος παραγωγης παραγωγων κιναζολινονης.
US5578593A (en) 1992-12-11 1996-11-26 Merck & Co., Inc. Spiro piperidines and homologs promote release of growth hormone
HUT72076A (en) 1992-12-11 1996-03-28 Merck & Co Inc Process for preparing spiro piperidines and homologs which promote release of growth hormone and pharmaceutical compositions containing them
US5602143A (en) * 1994-12-08 1997-02-11 Allergan Method for reducing intraocular pressure in the mammalian eye by administration of guanylate cyclase inhibitors
HUP9900028A3 (en) * 1995-10-17 1999-11-29 Astrazeneca Ab Pharmaceutically active quinazoline compounds, their production, use thereof and medicament containing them
CN1205008A (zh) * 1996-08-30 1999-01-13 协和发酵工业株式会社 咪唑并喹唑啉衍生物
US6509334B1 (en) 1999-05-04 2003-01-21 American Home Products Corporation Cyclocarbamate derivatives as progesterone receptor modulators
US6358948B1 (en) 1999-05-04 2002-03-19 American Home Products Corporation Quinazolinone and benzoxazine derivatives as progesterone receptor modulators
WO2000066560A1 (en) * 1999-05-04 2000-11-09 American Home Products Corporation Quinazolinone and benzoxazine derivatives as progesterone receptor modulators
US6498154B1 (en) 1999-05-04 2002-12-24 Wyeth Cyclic regimens using quinazolinone and benzoxazine derivatives
ES2226833T3 (es) 1999-05-04 2005-04-01 Wyeth Composiciones anticonceptivas que contienen agentes antiprogestinicos y progestinicos.
AU2274101A (en) 1999-12-21 2001-07-03 Merck & Co., Inc. Inhibitors of prenyl-protein transferase
UA73119C2 (en) 2000-04-19 2005-06-15 American Home Products Corpoir Derivatives of cyclic thiocarbamates, pharmaceutical composition including noted derivatives of cyclic thiocarbamates and active ingredients of medicines as modulators of progesterone receptors

Also Published As

Publication number Publication date
MA27001A1 (fr) 2004-12-20
ES2288552T3 (es) 2008-01-16
HUP0303637A2 (hu) 2004-03-01
NO326086B1 (no) 2008-09-15
DE60221233T2 (de) 2008-04-03
EA006815B1 (ru) 2006-04-28
AU2002304800B2 (en) 2007-08-30
JP4086663B2 (ja) 2008-05-14
PE20021010A1 (es) 2003-02-01
CZ20032451A3 (cs) 2004-09-15
OA12454A (en) 2004-09-30
PT1373224E (pt) 2007-09-25
TNSN03076A1 (en) 2005-12-23
JP2004529123A (ja) 2004-09-24
CA2441313A1 (en) 2002-09-26
NO20034187L (no) 2003-10-15
PL367058A1 (en) 2005-02-21
CU23218A3 (es) 2007-07-20
KR20030086315A (ko) 2003-11-07
BG108181A (bg) 2004-09-30
US20040214843A1 (en) 2004-10-28
CA2441313C (en) 2009-03-31
IS6934A (is) 2003-08-29
EP1373224A1 (en) 2004-01-02
SI1373224T1 (sl) 2007-10-31
BR0208192A (pt) 2004-03-02
HRP20030740A2 (en) 2005-06-30
EE200300459A (et) 2004-02-16
SK11562003A3 (sk) 2005-01-03
CN100447136C (zh) 2008-12-31
CN1498212A (zh) 2004-05-19
IS2529B (is) 2009-07-15
US20020198198A1 (en) 2002-12-26
ATE367381T1 (de) 2007-08-15
MY142045A (en) 2010-08-30
TWI267509B (en) 2006-12-01
EP1801106A2 (en) 2007-06-27
PA8541601A1 (es) 2003-05-14
DE60221233D1 (de) 2007-08-30
ECSP034750A (es) 2003-10-28
WO2002074754A1 (en) 2002-09-26
HUP0303637A3 (en) 2004-07-28
DK1373224T3 (da) 2007-10-15
NO20034187D0 (no) 2003-09-19
IL157659A0 (en) 2004-03-28
RS50429B (sr) 2009-12-31
NZ527847A (en) 2005-06-24
WO2002076953A1 (en) 2002-10-03
MXPA03008485A (es) 2003-12-08
AP1699A (en) 2006-12-26
UA74243C2 (uk) 2005-11-15
AP2003002857A0 (en) 2003-09-30
EP1801106A3 (en) 2007-07-04
HK1061854A1 (zh) 2004-10-08
GEP20053631B (en) 2005-10-10
EA200300906A1 (ru) 2004-02-26
KR100617435B1 (ko) 2006-08-31
CY1106829T1 (el) 2012-05-23
SV2003000925A (es) 2003-05-20
US7214676B2 (en) 2007-05-08
ZA200306601B (en) 2004-08-25
US20070049558A1 (en) 2007-03-01
EP1373224B1 (en) 2007-07-18
GT200200053A (es) 2003-02-12
IL157659A (en) 2008-08-07
YU74003A (sh) 2006-05-25

Similar Documents

Publication Publication Date Title
AR033617A1 (es) Compuestos derivados espirociclicos, metodos para prepararlos y su uso como inhibidores de fosfodiesterasa-7
EA200501617A1 (ru) Новые гетероциклические соединения, применяемые для лечения нарушений аллергической или воспалительной природы: способы синтеза и содержащие их фармацевтические составы
HUP0402065A2 (hu) Heterobiciklikus szerkezetû hepatitis C vírus polimeráz inhibitorok, eljárás az elõállításukra és ezeket tartalmazó gyógyszerkészítmények
HUP0100950A2 (hu) Ciklusos aminovegyületek, alkalmazásuk gyógyászati készítmények előállítására és a vegyületeket tartalmazó gyógyászati készítmények
RU2010116253A (ru) Производные n-гидроксилсульфонамида как новые физиологически применимые доноры нитроксила
BG106527A (en) Pharmaceutically active sulfonamide derivatives
AR034203A1 (es) Derivados de 1-aril- o 1-alquilsulfonilbenzazol como ligandos de 5-hidroxitriptamina-6, un metodo para su preparacion, composicion farmaceutica y el uso de los mismos para la fabricacion de un medicamento
DE60322267D1 (de) Chinolinderivate als glucokinase liganden
PE20070798A1 (es) Compuestos heterociclicos como inhibidores de aspartil proteasas
RU2005106353A (ru) Производные гидантоина и их применение в качестве ингибиторов тасе
DE602004008098D1 (de) Substituierte 2h-ä1,2,4ütriazoloä4,3-aüpyrazine als gsk-3-inhibitoren
HUP0401538A2 (hu) Új, helyettesített aminometilcsoportot tartalmazó N-(arilszulfonil)-béta-aminosav-származékok, előállításukra alkalmas eljárás és a vegyületeket tartalmazó gyógyászati készítmények
ATE556058T1 (de) 1-(2h)-isochinolonderivat
AR063804A1 (es) Compuestos de azoniabiciclo[2.2.2]octano
EA200401612A1 (ru) Противоаллергические средства
CO5601011A2 (es) Derivados de 3-ciclil-5-(anillo de 5 miembros que contiene nitrogeno) metil-oxazolidinona y su uso como agentes antibacterianos
HRP20041137B1 (hr) Indolni, azaindolni i srodni heterocikliäśni 4-alkenil piperidinski amidi
AR064414A1 (es) Derivados de 1-azoniabiciclo[2, 2, 2]octano y 1-azabiciclo[2, 2, 2]oct-3-ilo, un proceso para su preparacion, una composicion farmaceutica que los comprende, procedimiento de obtencion de la misma, su uso en la elaboracion de un medicamento para el tratamiento de epoc y un producto farmaceutico que
AR035235A1 (es) Derivados heterocicliloxi-,-tioxi- y -aminobenzazol como ligandos de 5-hidroxitriptamina-6, un procedimiento para su preparacion, composicion farmaceutica, y el uso de dichos derivados para la manufactura de un medicamento
AR045040A1 (es) Derivados de compuestos espiroazabiciclicos, composiciones farmaceuticas que los contienen y su uso en la preparacion de medicamentos
SE0201937D0 (sv) Therapeutic agents
YU67601A (sh) 1-arensulfonil-2-aril-pirolidin i derivati piperidina
RU2009102270A (ru) Производные тиазолилмочевины в качестве ингибиторов фосфатидилинозитол-3-киназы
SE0300091D0 (sv) Novel compounds
HUP0303801A2 (hu) Heterociklusos alkoxi-, alkil-tio- és alkil-amino-benzazol-származékok, mint 5-hidroxi-triptamin-6 ligandumok, eljárás az előállításukra és ezeket tartalmazó gyógyszerkészítmények

Legal Events

Date Code Title Description
FG Grant, registration