WO2001098273A1 - Novel compounds - Google Patents
Novel compounds Download PDFInfo
- Publication number
- WO2001098273A1 WO2001098273A1 PCT/SE2001/001377 SE0101377W WO0198273A1 WO 2001098273 A1 WO2001098273 A1 WO 2001098273A1 SE 0101377 W SE0101377 W SE 0101377W WO 0198273 A1 WO0198273 A1 WO 0198273A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- phenyl
- acetamide
- amino
- piperidinyl
- hydroxy
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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 to ring carbon atoms
- C07D211/56—Nitrogen atoms
- C07D211/58—Nitrogen atoms attached in position 4
-
- 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
- A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to novel compounds, processes for their preparation, pharmaceutical compositions containing them and their use in therapy.
- Chemokines play an important role in immune and inflammatory responses in various diseases and disorders, including asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis. These small secreted molecules are a growing superfamily of 8-14 kDa proteins characterised by a conserved four cysteine motif. The chemokine superfamily can be divided into two main groups exhibiting characteristic structural motifs, the Cys-X-Cys (C-X-C) and Cys-Cys (C-C) families. These are distinguished on the basis of a single amino acid insertion between the NH-proximal pair of cysteine residues and sequence similarity.
- the C-X-C chemokines include several potent chemoattractants and activators of neutrophils such as interleukin-8 (IL-8) and neutrophil-activating peptide 2 (NAP-2).
- IL-8 interleukin-8
- NAP-2 neutrophil-activating peptide 2
- the C-C chemokines include potent chemoattractants of monocytes and lymphocytes but not neutrophils such as human monocyte chemotactic proteins 1-3 (MCP-1, MCP-2 and MCP-3), RANTES (Regulated on Activation, Normal T Expressed and Secreted), eotaxin and the macrophage inflammatory proteins l ⁇ and l ⁇ (MlP-l and MlP-l ⁇ ).
- chemokines are mediated by subfamilies of G protein-coupled receptors, among which are the receptors designated CCR1, CCR2, CCR2A, CCR2B, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3 and CXCR4.
- G protein-coupled receptors among which are the receptors designated CCR1, CCR2, CCR2A, CCR2B, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CCR10, CXCR1, CXCR2, CXCR3 and CXCR4.
- each R independently represents halogen, cyano, nitro, carboxyl, hydroxyl,
- Z represents a bond or a group (CH 2 ) q where q is 1 or 2;
- Z represents a bond or a group CH 2 , with the proviso that Z and Z do not both simultaneously represent a bond;
- Q represents an oxygen or sulphur atom or a group CH 2 or NH
- R represents a group
- n 0, 1 or 2;
- 3 eac R independently represents a C j -Cg alkyl, Ci-Cg alkoxycarbonyl, -CH 2 OH or carboxyl group;
- R , R , R and R each independently represent a hydrogen atom or a C j -0 6 alkyl group, or R , R , R and R together represent a C1-C 4 alkylene chain linking the two carbon atoms to which they are attached to form a 4- to 7-membered saturated carbocycle, or R , R and R each represent a hydrogen atom and R and R together with the carbon atoms to which they are attached form a 5- to 6-membered saturated carbocycle; R represents a hydrogen atom, a C r C 6 alkyl group or is linked to R as defined 5 above;
- R and R each independently represent a hydrogen atom or a C Cg alkyl group, or
- R and R together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle
- R and R each independently represent a hydrogen atom or a C r C 6 alkyl group l o optionally substituted by C j -Cg alkoxycarbonyl;
- R represents a hydrogen atom or a C j -Cg alkyl group
- R represents a hydrogen atom, or a C r C 6 alkyl group optionally substituted by carboxyl, C r C 6 alkoxy or C r C 6 alkoxycarbonyl;
- R represents carboxyl, C r C 6 alkoxy, C r C 6 alkylcarbonyl, C r C 6 alkoxycarbonyl, 15 C r C 6 alkoxycarbonylC r C 6 alkyl or a group -NR 17 R 18 , -NHSO 2 CH 3 , -C(O)NR 17 R 18 , -NHC(O)NR 17 R 18 , -OC(O)NR 17 R 18 , -OCH 2 C(O)NR 17 R 18 , -NHC(O)OR 19 or -NHC(O)R 20 ; t is 0, 1, 2 or 3; each R independently represents halogen, cyano, nitro, carboxyl, hydroxyl, 20 C ⁇ -Cg cycloalkyl, C j -Cg alkoxy, C j -Cg alkoxycarbonyl, C j - haloalkyl,
- R and R each independently represent a hydrogen atom, or a C j -Cg alkyl group
- R represents a group C r C 6 alkyl, C 2 -C 6 alkenyl, C 3 -C 6 cycloalkyl, adamantyl, C 5 - cycloalkenyl, phenyl or a saturated or unsaturated 5- to 10-membered heterocyclic ring system comprising at least one heteroatom selected from nitrogen, oxygen and sulphur, each of which may be optionally substituted by one or more substituents independently selected from nitro, hydroxyl, oxo, halogen, carboxyl, C r C 6 alkyl,
- R and R each independently represent a hydrogen atom or a Ci -C 6 alkyl group, or
- R and R together with the nitrogen atom to which they are attached form a 4- to 7- membered saturated heterocycle
- R and R each independently represent a hydrogen atom or a Ci-Cg alkyl group optionally substituted by C j -C 6 alkoxycarbonyl; v is 0 or 1 ;
- R represents a hydrogen atom or a C j -C 6 alkyl group; represents a hydrogen atom, or a C j -Cg alkyl group optionally substituted by carboxyl, C J -C6 alkoxy or C C 6 alkoxycarbonyl; and
- 27 R represents a C j -C 6 alkyl, amino (-NH 2 ) or ph ⁇ or a pharmaceutically acceptable salt or solvate thereof.
- R the saturated or unsaturated 5- to 10-membered heterocyclic ring system may be aliphatic or aromatic.
- the integer m is preferably 1 or 2.
- Each R independently represents halogen (e.g. chlorine, fluorine, bromine or iodine), cyano, nitro, carboxyl, hydroxyl, C 3 -C 6 cycloalkyl (cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), Ci-Cg, preferably C 1 -C4, alkoxy (e.g. methoxy, ethoxy, n-propoxy or n-butoxy), C j -Cg, preferably C1-C 4 , alkoxycarbonyl (e.g.
- C r C 6 preferably C r C , haloalkyl (e.g. trifluoromethyl), C r Cg, preferably C ⁇ -C 4 , haloalkoxy (e.g. trifluoromethoxy), -NR 9 R 10 , C 3 -C 6 cycloalkylamino (e.g. cyclopropylamino, cyclobutylamino, cyclopentylamino or cyclohexylamino), C ⁇ -C 6 , preferably C1-C 4 , alkylthio (e.g. methylthio or ethylthio),
- C j -Cg preferably C r C , alkylcarbonyl (e.g. methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, n-pentylcarbonyl or n-hexylcarbonyl), C ⁇ -C 6 , preferably C 1 -C 4 , alkylcarbonylamino (e.g. methylcarbonylamino or ethylcarbonylamino), sulphonamido,
- alkylcarbonyl e.g. methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, n-pentylcarbonyl or n-hexylcarbonyl
- C ⁇ -C 6 preferably C 1 -C 4
- alkylcarbonylamino e
- Ci-Cg preferably C C 4 , alkylsulphonyl (e.g. methylsulphonyl, ethylsulphonyl, n-propylsulphonyl, isopropylsulphonyl, n-butylsulphonyl, n-pentylsulphonyl or n-hexylsulphonyl), -C(O)NR U R 12 , -NR 13 C(O)-(NH) p R 14 , phenyl, or C Cg, preferably C1-C 4 , alkyl (e.g.
- each R independently represents halogen (particularly chlorine or fluorine), cyano, nitro, C ⁇ -C 6 alkoxy (especially methoxy), Cj-Cg alkylcarbonyl (especially methylcarbonyl) or C ⁇ -C 6 alkylcarbonylamino (particularly methylcarbonylamino).
- Each R especially represents a halogen atom.
- Q preferably represents an oxygen atom.
- Each R independently represents a C j -Cg, preferably C 1 -C 4 , alkyl (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl), C j -Cg, preferably
- alkoxycarbonyl e.g. methoxycarbonyl or ethoxycarbonyl
- -CH 2 OH or carboxyl
- R , R , R and R each independently represent a hydrogen atom or a C j -Cg, preferably C J -C 4 , alkyl (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl), or R , R , R and R together represent a Ci -C alkylene chain linking the two carbon atoms to which they are attached to form a 4- to 7-membered saturated carbocycle (e.g. cyclohexyl or preferably cyclopentyl), or each represent a hydrogen
- 6-membered saturated carbocycle preferably cyclopentyl
- R represents a hydrogen atom, a C Cg, preferably C Q ⁇ alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl) or is linked to R as defined above.
- C Q ⁇ alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- R and R each independently represent a hydrogen atom or a C j -C 6 , preferably C 1 -C 4 , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl,
- R and R each independently represent a hydrogen atom or a Cj-Cg, preferably C1-C4, alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl) optionally substituted by a C j -Cg, preferably Ci -C 4 , alkoxycarbonyl substituent group.
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- R represents a hydrogen atom or a C j -Cg, preferably C j ⁇ , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl).
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl.
- R represents a hydrogen atom, or a C Cg, preferably C j ⁇ , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl) optionally substituted by carboxyl, C Cg, preferably C1-C 4 , alkoxy or Ci-Cg, preferably C1-C 4 , alkoxycarbonyl.
- R represents carboxyl, C r C 6 , preferably C r C 4 , alkoxy (e.g.
- C r C 6 preferably C r C 4 , alkylcarbonyl (e.g. methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, n-butylcarbonyl, n-pentylcarbonyl or n-hexylcarbonyl), C r C 6 , preferably C r C 4 , alkoxycarbonyl (e.g. methoxycarbonyl or ethoxycarbonyl), C r C 6 alkoxycarbonylC r C 6 alkyl, preferably
- C r C 4 alkoxycarbonylC r C 4 alkyl e.g. methoxycarbonylmethyl or methoxycarbonylethyl
- a group -NR 17 R 18 -NHSO 2 CH 3 , -C(O)NR 17 R 18 , -NHC(O)NR 17 R 18 , -OC(O)NR 17 R 18 , -OCH 2 C(O)NR 17 R 18 , -NHC(O)OR 19 or -NHC(O)R 20 .
- R represents C r C 4 alkoxy (especially methoxy), C1-C 4 alkylcarbonyl (especially methylcarbonyl or ethylcarbonyl), C r C 4 alkoxycarbonylC r C 4 alkyl
- Each R independently represents halogen (e.g. chlorine, fluorine, bromine or iodine), cyano, nitro, carboxyl, hydroxyl, C 3 -C 6 cycloalkyl (cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), C r C 6 , preferably C r C 4 , alkoxy (e.g. methoxy, ethoxy, n-propoxy or n-butoxy), C r C 6 , preferably C ⁇ -C , alkoxycarbonyl (e.g. methoxycarbonyl or ethoxycarbonyl), C r C 6 , preferably C r C 4 , haloalkyl (e.g. trifluoromethyl),
- halogen e.g. chlorine, fluorine, bromine or iodine
- cyano nitro, carboxyl, hydroxyl, C 3 -C 6 cycloalkyl
- C r C 6 preferably C r C 4 , haloalkoxy (e.g. trifluoromethoxy), -NR R , C 3 -C 6 cycloalkylamino (e.g. cyclopropylamino, cyclobutylamino, cyclopentylamino or cyclohexylamino), C r C 6 , preferably C 1 -C 4 , alkylthio (e.g. methylthio or ethylthio), Cj-C ⁇ , preferably C1-C 4 , alkylcarbonyl (e.g.
- alkylsulphonyl e.g. methylsulphonyl, ethylsulphonyl, n-propylsulphonyl, isopropylsulphonyl, n-butylsulphonyl, n-pentylsulphonyl or n-hexylsulphonyl
- -C(O)NR 23 R 24 e.g. methylsulphonyl, ethylsulphonyl, n-propylsulphonyl, isopropylsulphonyl, n-butylsulphonyl, n-pentylsulphonyl or n-hexylsulphonyl
- -C(O)NR 23 R 24 e.g. methylsulphonyl, ethylsulphonyl, n-propylsulphonyl, isopropylsulphonyl, n-butyls
- each R independently represents halogen (particularly chlorine or fluorine), cyano, C r C alkoxy (especially methoxy), C r C 4 alkoxycarbonyl (especially methoxycarbonyl), C r C 4 haloalkyl (especially trifluoromethyl), C r C 4 alkylcarbonyl (particularly methylcarbonyl), phenyl or C r C 4 alkyl (e.g. methyl or tert-butyl).
- halogen particularly chlorine or fluorine
- cyano particularly methoxy
- C r C 4 alkoxycarbonyl especially methoxycarbonyl
- C r C 4 haloalkyl especially trifluoromethyl
- C r C 4 alkylcarbonyl particularly methylcarbonyl
- phenyl or C r C 4 alkyl e.g. methyl or tert-butyl
- R and R each independently represent a hydrogen atom or a C j -Cg, preferably
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- C j -Cg preferably Ci -C4, alkoxycarbonyl, especially methoxycarbonyl, or R and R together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocycle (preferably pyrrolidinyl or piperidinyl).
- R represents a hydrogen atom or a C r C 6 , preferably C C 4 , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl) optionally substituted by carboxyl or, more preferably, C r C 6 , preferably C r C , alkoxycarbonyl, especially methoxycarbonyl.
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- R represents a group C j -Cg, preferably C r C 5 , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl), C 2 -C 6 , preferably C2-C4, alkenyl, C 3 -Cg cycloalkyl (cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl), adamantyl, C 5 -C 6 cycloalkenyl, phenyl or a saturated or unsaturated 5- to 10-membered heterocyclic ring system comprising at least one heteroatom (e.g.
- one, two, three or four heteroatoms selected from nitrogen, oxygen and sulphur, each of which may be optionally substituted by one or more (e.g. one, two, three or four) substituents independently selected from nitro, hydroxyl, oxo, halogen (e.g. fluorine, chlorine, bromine or iodine), carboxyl, C j -0 6 , preferably Ci -C 4 , alkyl (e.g.
- C r C 6 preferably C r C 4 , alkoxy (e.g. methoxy, ethoxy, n-propoxy or n-butoxy), C r C 6 , preferably alkylthio (e.g. methylthio or ethylthio), C r C 6 , preferably alkylcarbonyl (e.g.
- C r C 6 preferably C r C 4 , alkoxycarbonyl (e.g. methoxycarbonyl or ethoxycarbonyl), phenyl and -NHC(O)-R 27.
- the saturated or unsaturated 5- to 10-membered heterocyclic ring system may be monocyclic or polycyclic (e.g. bicyclic) and may comprise up to four heteroatoms independently selected from nitrogen, oxygen and sulphur.
- ring systems that may be used include pyrrolidinyl, piperidinyl, pyrazolyl, thiazolidinyl, thienyl, isoxazolyl, thiadiazolyl, pyrrolyl, furanyl, thiazolyl, indolyl, quinolinyl, benzimidazolyl, triazolyl, tetrazolyl and pyridinyl.
- R 21 and R 22 each independently represent a hydrogen atom or a Ci -C 6 , preferably
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl,' n-pentyl or n-hexyl
- R 21 and R 22 together with the nitrogen atom to which they are attached form a 4- to 7-membered saturated heterocycle (preferably pyrrolidinyl or piperidinyl).
- R 23 and R 24 each independently represent a hydrogen atom or a C C 6 , preferably C J -C 4 , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl) optionally substituted by a C Cg, preferably C1-C 4 , alkoxycarbonyl substituent group.
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- R 25 represents a hydrogen atom or a C Cg, preferably C ! -C 4 , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl).
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl.
- R represents a hydrogen atom, or a C r C 6 , preferably C C 4 , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl) optionally substituted by carboxyl, C r C 6 , preferably C r C 4 , alkoxy or C r C 6 , preferably C1-C 4 , alkoxycarbonyl.
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- R represents a Cj-Cg, preferably C 1 -C 4 , alkyl group (e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl), amino or phenyl group.
- alkyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- amino or phenyl group e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl or n-hexyl
- Preferred compounds of the invention include:
- the present invention further provides a process for the preparation of a compound of formula (I) as defined above which comprises (a) reacting a compound of general formula
- L represents a hydrogen atom or a leaving group (e.g. Li when Q is CH 2 ) and Q
- the process of the invention may conveniently be carried out in a solvent, e.g. an organic solvent such as an alcohol (e.g. methanol or ethanol), a hydrocarbon (e.g. toluene) or acetonitrile at a temperature of, for example, 15°C or above such as a temperature in the range from 20 to 120°C.
- a solvent e.g. an organic solvent such as an alcohol (e.g. methanol or ethanol), a hydrocarbon (e.g. toluene) or acetonitrile at a temperature of, for example, 15°C or above such as a temperature in the range from 20 to 120°C.
- Compounds of formula (I) can be converted into further compounds of formula (I) using standard procedures.
- a compound of formula (I) in which R represents - ⁇ HC(O)CH 3 can be converted to a further compound of formula (I) in which R represents -NH 2 by a hydrolysis reaction in the presence of hydrochloric acid.
- the compounds of formula (I) above may be converted to a pharmaceutically acceptable salt or solvate thereof, preferably an acid addition salt such as a hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate, oxalate, methanesulphonate or -toluenesulphonate.
- a pharmaceutically acceptable salt or solvate thereof preferably an acid addition salt such as a hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, tartrate, citrate, oxalate, methanesulphonate or -toluenesulphonate.
- Compounds of formula (I) are capable of existing in stereoisomeric forms. It will be understood that the invention encompasses the use of all geometric and optical isomers of the compounds of formula (I) and mixtures thereof including racemates. The use of tautomers and mixtures thereof also form an aspect of the present invention. Preferred . .
- the compounds of formula (I) have activity as pharmaceuticals, in particular as modulators of chemokine receptor (especially MlP-l ⁇ chemokine receptor) activity, and may be used in the treatment of autoimmune, inflammatory, proliferative and hyperproliferative diseases and immunologically-mediated diseases including rejection of transplanted organs or tissues and Acquired Immunodeficiency Syndrome (AIDS).
- modulators of chemokine receptor especially MlP-l ⁇ chemokine receptor
- AIDS Acquired Immunodeficiency Syndrome
- COPD chronic obstructive pulmonary disease
- asthma such as bronchial, allergic, intrinsic, extrinsic and dust asthma, particularly chronic or inveterate asthma (e.g.
- bronchitis acute, allergic, atrophic rhinitis and chronic rhinitis including rhinitis caseosa, hypertrophic rhinitis, rhinitis purulenta, rhinitis sicca and rhinitis medicamentosa; membranous rhinitis including croupous, fibrinous and pseudomembranous rhinitis and scrofoulous rhinitis; seasonal rhinitis including rhinitis nervosa (hay fever) and vasomotor rhinitis; sarcoidosis, farmer's lung and related diseases, fibroid lung and idiopathic interstitial pneumonia;
- NSCLC non-small cell lung cancer
- squamous sarcoma squamous sarcoma
- cystic fibrosis (9) cystic fibrosis, stroke, re-perfusion injury in the heart, brain, peripheral limbs and sepsis.
- the present invention provides a compound of formula (I), or a pharmaceutically- acceptable salt or solvate thereof, as hereinbefore defined for use in therapy.
- the present invention provides the use of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined in the manufacture of a medicament for use in therapy.
- the term “therapy” also includes “prophylaxis” unless there are specific indications to the contrary.
- the terms “therapeutic” and ' “therapeutically” should be construed accordingly.
- the invention also provides a method of treating an inflammatory disease in a patient suffering from, or at risk of, said disease, which comprises administering to the patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined.
- the invention still further provides a method of treating an airways disease in a patient suffering from, or at risk of, said disease, which comprises administering to the patient a therapeutically effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined.
- the dosage administered will, of course, vary with the compound employed, the mode of administration, the treatment desired and the disorder indicated.
- the daily dosage of the compound of formula (I) may be in the range from 0.001 mg/kg to 30 mg/kg.
- the compounds of formula (I) and pharmaceutically acceptable salts and solvates thereof may be used on their own but will generally be administered in the form of a pharmaceutical composition in which the formula (I) compound/salt/solvate (active ingredient) is in association with a pharmaceutically acceptable adjuvant, diluent or carrier.
- the pharmaceutical composition will preferably comprise from 0.05 to 99 %w (per cent by weight), more preferably from 0.05 to 80 %w, still more preferably from 0.10 to 70 %w, and even more preferably from 0.10 to 50 %w, of active ingredient, all percentages by weight being based on total composition.
- the present invention also provides a pharmaceutical composition
- a pharmaceutical composition comprising a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined, in association with a pharmaceutically acceptable adjuvant, diluent or carrier.
- the invention further provides a process for the preparation of a pharmaceutical composition of the invention which comprises mixing a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, as hereinbefore defined, with a pharmaceutically acceptable adjuvant, diluent or carrier.
- compositions may be administered topically (e.g. to the lung and/or airways or to the skin) in the form of solutions, suspensions, heptafluoroalkane aerosols and dry powder formulations; or systemically, e.g. by oral administration in the form of tablets, capsules, syrups, powders or granules, or by parenteral administration in the form of solutions or suspensions, or by subcutaneous administration or by rectal administration in the form of suppositories or transdermally.
- Example 1 N-[2-(3- ⁇ [l-(3,4-dichlorobenzylpiperidinyl]aminohydroxypropoxy)phenyl]acetamide
- the mixture of N-Acetyl-2-(2,3-epoxypropoxy)aniline (120mg, 0,58mmol) and the above starting material (150mg, 0,58mmol) in ethanol (10ml 99.5%) was refluxed for 3hrs.
- the solvent distilled off under reduced pressure, the resulting residue was purified by silica gel column chromatography (eluant: dichloromethane/methanol 15:1) to give 108mg of the title compound as a gum. Addition of 1.0M ethereal HCI solution gave a white solid product.
- (2S)-2-[(2-nitrophenoxy)methyl]oxirane (1.17 g, 6 mmol) was dissolved in ethyl acetate (50 ml). Platinum on charcoal (0.50 g) was added, and the mixture was stirred in the atmosphere of hydrogen for 3 h at room temperature and atmospheric pressure. The catalyst was filtered and washed on the filter with ethyl acetate (10 ml). Acetic anhydride (1.23g, 1.13.ml, 12 mmol) and ethyldi(f-propyl)amine (1.55 g, 2.05 ml, 12 mmol) were added to the solution.
- reaction mixture was filtered through celite®.
- the organic phase was washed with 10%> tartaric acid (500 ml), saturated NaHCO 3 (300 ml) and brine (300 ml).
- the organic phase was dried (MgSO 4 ) and evaporated to give ca 150 g of a yellow oil.
- the crude material was chromatographed (1 kg silica, Heptane/EtOAc 100:0 to 50:50 gradually increased polarity) to give 48.8 g (84%) of the sub-title compound as a yellow oil.
- the compound was pure enough to use further without any additional purification.
- the organic phase was collected and the aqueous phase was washed with EtO Ac (2 x 200 ml).
- the combined organic phases were washed with water (200 ml), 1M NaOH (2 x 200 ml) and brine (150 ml).
- the organic solution was dried over N- ⁇ S ,, and concentrated in vacuo after filtration.
- the crude material was purified on silica (Heptane/EtOAc 5:1 to 1:1, gradually increasing the polarity), eluting 18.5 g (92%>) of the sub-title compound.
- the optical purity was 97.4 %, according to chiral HPLC (Chiralpak TM, iso-hexane/iso- propanol 95:5).
- Epoxide E N- ⁇ 2-[(2-Methyl-2-oxiranyl)methoxy]phenyl ⁇ benzamide
- N-(2-hydroxyphenyl)benzamide 159 mg, 0.75 mmol
- 2-(chloromethyl)-2- methyloxirane 1.60 g, 15 mmol
- benzyltriethylammonium chloride 27 mg, 0.12 mmol
- N-Methyl-2-[(2-methyl-2-oxiranyl)methoxy]benzamide was prepared from 2-hydroxy-N-methylbenzamide (prepared according to Cohen et al, J. Am. Chem. Soc, 1998, 20, 6277 - 6286.) according to the method described for N- ⁇ 2-[(2- methyl-2-oxiranyl)methoxy]phenyl ⁇ benzamide.
- Epoxide K N-MethyI-2-oxiranylmethoxy-benzamide
- 2-Hydroxy-N-methyl-benzamide 0.5g, 3.31 mmol prepared according to Cohen, Seth M et al j. Am. Chem. Soc, (1998), 120(25), 6277-6286.
- cesium carbonate 2.16g, 6.62mmol
- epibromohydrin 0.274ml, 3.31mmol
- the mixture was heated at 50°C for 2 hours and then after cooling to room temperature partitioned between water(50 ml)and dichloromethane (100ml). The dichloromethane was dried and evaporated . Chromatography (EtOAc) gave 0.43g (64%) of the product as a solid.
- N-(2-Oxiranylmethoxy-phenyl)-benzamide 0.2ml, 0.1M in DMSO
- EtOH 0.2ml, 0.1M in EtOH
- the assay measured the chemotactic response elicited by MlP-l ⁇ chemokine in the human monocytic cell line THP-1.
- the compounds of the Examples were evaluated by their ability to depress the chemotactic response to a standard concentration of MlP-l ⁇ chemokine.
- THP-1 cells are routinely cultured in RPMI- 1640 medium supplemented with 10% heat inactivated fetal calf serum and glutamax but without antibiotics. Optimal growth of the cells requires that they are passaged every 3 days and that the minimum subculture density is 4x10+5 cells/ml.
- Cells were removed from the flask and washed by centrifugation in RPMI+10%HIFCS+glutamax. The cells were then resuspended at 2x10+7 cells/ml in fresh medium (RPMI+10%HIFCS+glutamax) to which was added calcein-AM (5 ⁇ l of stock solution to 1 ml to give a final concentration of 5x10 " M). After gentle mixing the cells were incubated at 37°C in a CO 2 incubator for 30 minutes. The cells were then diluted to 50 ml with medium and washed twice by centrifugation at 400xg.
- Labelled cells were then resuspended at a cell concentration of 1x10+7 cells/ml and incubated with an eeqquuaall vvoolluummee ooff MMllPP--ll ⁇ aannttaaggoonniisstt ((11(0 " 10, M , t ,o , 10 ⁇ - " 6 M, final concentration) for 30 minutes at 37°C in a humidified CO 2 incubator.
- Chemotaxis was performed using Neuroprobe 96-well chemotaxis plates employing 8 ⁇ m filters (cat no. 101-8). Thirty microlitres of chemoattractant supplemented with various concentrations of antagonists or vehicle were added to the lower wells of the plate in triplicate. The filter was then carefully positioned on top and then 25 ⁇ l of cells preincubated with the corresponding concentration of antagonist or vehicle were added to the surface of the filter. The plate was then incubated for 2 hours at 37°C in a humidified CO 2 incubator. The cells remaining on the surface were then removed by adsorption and the whole plate was centrifuged at 2000 rpm for 10 minutes.
- the filter was then removed and the cells that had migrated to the lower wells were quantified by the fluorescence of cell associated calcein-AM. Cell migration was then expressed in fluorescence units after subtraction of the reagent blank and values were standardized to % migration by comparing the fluorescence values with that of a known number of labelled cells. The effect of antagonists was calculated as % inhibition when the number of migrated cells were compared with vehicle.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
Claims
Priority Applications (22)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
UA2002129741A UA75078C2 (en) | 2000-12-05 | 2001-06-14 | Benzylpiperidines and benzyloyrrolidines, their pharmaceutically acceptable salts or solvates, method for obtaining thereof (variants), pharmaceutical composition based thereon, a method for obtaining such composition, a method for treatment of inflammatory diseases, in particular those of respiratory tracts with use of said compounds |
AU2001274763A AU2001274763B2 (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
MXPA02012425A MXPA02012425A (en) | 2000-06-20 | 2001-06-14 | Novel compounds. |
CNB018142141A CN1307157C (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
BR0111667-3A BR0111667A (en) | 2000-06-20 | 2001-06-14 | New compounds |
JP2002504229A JP4022142B2 (en) | 2000-06-20 | 2001-06-14 | New compounds |
NZ523047A NZ523047A (en) | 2000-06-20 | 2001-06-14 | Phenyl derivatives, processes for their preparation and pharmaceutical compositions containing them |
HU0301187A HUP0301187A3 (en) | 2000-06-20 | 2001-06-14 | Novel benzyl-piperidine-derivatives, process for their preparation and pharmaceutical compositions containing them |
US10/311,841 US6911458B2 (en) | 2000-06-20 | 2001-06-14 | Compounds |
EP01941406A EP1299357A1 (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
EEP200200704A EE05157B1 (en) | 2000-06-20 | 2001-06-14 | Derivatives of N - [(substituted benzyl) -4-piperidinyl or pyrrolidinyl] amino-hydroxyalkoxyphenyls, their preparation and their use in medicine |
IL15316701A IL153167A0 (en) | 2000-06-20 | 2001-06-14 | Phenyl derivatives, a process for their preparation, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy |
AU7476301A AU7476301A (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
CA002414095A CA2414095C (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
SK1793-2002A SK17932002A3 (en) | 2000-06-20 | 2001-06-14 | Phenyl derivatives, process for the preparation thereof, pharmaceutical compositions comprising the same and their therapeutical use |
KR1020027017281A KR100799061B1 (en) | 2000-06-20 | 2001-06-14 | Novel Compounds |
PL366198A PL203936B1 (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
IL153167A IL153167A (en) | 2000-06-20 | 2002-11-28 | Phenyl derivatives, a process for their preparation, pharmaceutical compositions containing them and use thereof in the manufacture of medicaments for therapy |
NO20026064A NO324698B1 (en) | 2000-06-20 | 2002-12-17 | New Compounds, Pharmaceutical Preparations Containing Such, Methods for their Preparation and Uses thereof |
IS6658A IS6658A (en) | 2000-06-20 | 2002-12-17 | New compounds |
US10/994,683 US7528156B2 (en) | 2000-06-20 | 2004-11-22 | Compounds |
US12/434,955 US20090306141A1 (en) | 2000-06-20 | 2009-05-04 | Novel Compounds |
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SE0002331A SE0002331D0 (en) | 2000-06-20 | 2000-06-20 | Novel compounds |
SE0002331-7 | 2000-06-20 | ||
SE0004480-0 | 2000-12-05 | ||
SE0004480A SE0004480D0 (en) | 2000-12-05 | 2000-12-05 | Novel compounds |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10311841 A-371-Of-International | 2001-06-14 | ||
US10/994,683 Continuation US7528156B2 (en) | 2000-06-20 | 2004-11-22 | Compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2001098273A1 true WO2001098273A1 (en) | 2001-12-27 |
Family
ID=26655154
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/SE2001/001377 WO2001098273A1 (en) | 2000-06-20 | 2001-06-14 | Novel compounds |
Country Status (22)
Country | Link |
---|---|
US (3) | US6911458B2 (en) |
EP (1) | EP1299357A1 (en) |
JP (1) | JP4022142B2 (en) |
KR (1) | KR100799061B1 (en) |
CN (1) | CN1307157C (en) |
AR (1) | AR028948A1 (en) |
AU (2) | AU7476301A (en) |
BR (1) | BR0111667A (en) |
CA (1) | CA2414095C (en) |
CZ (1) | CZ20024146A3 (en) |
EE (1) | EE05157B1 (en) |
HU (1) | HUP0301187A3 (en) |
IL (2) | IL153167A0 (en) |
IS (1) | IS6658A (en) |
MX (1) | MXPA02012425A (en) |
MY (1) | MY136520A (en) |
NO (1) | NO324698B1 (en) |
NZ (1) | NZ523047A (en) |
PL (1) | PL203936B1 (en) |
RU (2) | RU2419608C2 (en) |
SK (1) | SK17932002A3 (en) |
WO (1) | WO2001098273A1 (en) |
Cited By (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005023771A1 (en) * | 2003-09-05 | 2005-03-17 | Ono Pharmaceutical Co., Ltd. | Chemokine receptor antagonist and medical use thereof |
WO2007015666A1 (en) * | 2005-08-02 | 2007-02-08 | Astrazeneca Ab | New salt i |
WO2007015667A1 (en) * | 2005-08-02 | 2007-02-08 | Astrazeneca Ab | New salt ii |
WO2007015664A1 (en) * | 2005-08-01 | 2007-02-08 | Astrazeneca Ab | Novel piperidine derivatives as chemokine receptor modulators useful for the treatment of respiratory diseases. |
WO2007015668A1 (en) * | 2005-08-02 | 2007-02-08 | Astrazeneca Ab | New salt iii |
WO2007053082A1 (en) * | 2005-11-02 | 2007-05-10 | Astrazeneca Ab | Novel 1 -benzyl-4-piperidinamines that are useful in the treatment of copd and asthma |
WO2007102767A1 (en) * | 2006-03-07 | 2007-09-13 | Astrazeneca Ab | Piperidine derivatives, their process for preparation, their use as therapeutic agents and pharmaceutical compositions containing them |
WO2007102768A1 (en) * | 2006-03-07 | 2007-09-13 | Astrazeneca Ab | Piperidine derivatives, their process for preparation, their use as therapeutic agents and pharmaceutical compositions containing them . |
WO2008010764A2 (en) * | 2006-07-18 | 2008-01-24 | Astrazeneca Ab | A process for the preparation of substituted 2-acetylamino-alkoxyphenyl |
WO2008103125A1 (en) * | 2007-02-23 | 2008-08-28 | Astrazeneca Ab | Novel combination of compounds to be used in the treatment of airway diseases, especially chronic obstructive pulmonary disease (copd) and asthma |
WO2008121065A1 (en) * | 2007-03-30 | 2008-10-09 | Astrazeneca Ab | Novel pyrrolidine derivatives as antagonists of the chemokine receptor |
US7449475B2 (en) | 2002-07-08 | 2008-11-11 | Astrazeneca Ab | Tricyclic spiropiperidines or spiropyrrolidines |
EP2027105A2 (en) * | 2006-05-10 | 2009-02-25 | AstraZeneca AB | Novel process for preparing intermediates of ccr antagonists |
US7498338B2 (en) | 2003-11-20 | 2009-03-03 | Astrazeneca Ab | Compounds |
US7524856B2 (en) | 2003-12-22 | 2009-04-28 | Astrazeneca Ab | Tricyclic spiroderivatives as modulators of chemokine receptor activity |
US7528156B2 (en) | 2000-06-20 | 2009-05-05 | Astrazeneca Ab | Compounds |
US7851615B2 (en) | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
WO2011012897A1 (en) | 2009-07-31 | 2011-02-03 | Astrazeneca Ab | New combinations for the treatment of asthma |
WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
WO2011073662A1 (en) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Combination of a benzoxazinone and a further agent for treating respiratory diseases |
US8017762B2 (en) | 2003-04-17 | 2011-09-13 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
EP2364704A1 (en) | 2007-02-08 | 2011-09-14 | AstraZeneca AB | Combination of beta-adrenoceptor agonist and corticosteroid |
WO2012085583A1 (en) | 2010-12-23 | 2012-06-28 | Astrazeneca Ab | New compound |
WO2012085582A1 (en) | 2010-12-23 | 2012-06-28 | Astrazeneca Ab | Compound |
WO2012163848A1 (en) | 2011-05-27 | 2012-12-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of crohn's disease |
US8344125B2 (en) | 2003-04-17 | 2013-01-01 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US8426377B2 (en) | 2003-04-17 | 2013-04-23 | Alnylam Pharmaceuticals, Inc. | iRNA agents with biocleavable tethers |
US8466153B2 (en) | 2006-12-08 | 2013-06-18 | Janssen Pharmaceutica N.V. | Piperidinylamino-pyridazines and their use as fast dissociating dopamine 2 receptor antagonists |
US8530474B2 (en) | 2008-07-03 | 2013-09-10 | Janssen Pharmaceutica Nv | Substituted 6-(1-piperazinyl)-pyridazines as 5-HT6 receptor antagonists |
US8791120B2 (en) | 2007-02-13 | 2014-07-29 | Janssen Pharmaceutica Nv | Fast-dissociating dopamine 2 receptor antagonists |
US8796436B2 (en) | 2003-04-17 | 2014-08-05 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US8895562B2 (en) | 2008-07-31 | 2014-11-25 | Janssen Pharmaceutica Nv | Piperazin-1-yl-trifluoromethyl-substituted-pyridines as fast dissociating dopamine 2 receptor antagonists |
US8906921B2 (en) | 2007-04-23 | 2014-12-09 | Janssen Pharmaceutica Nv | 4-alkoxypyridazine derivatives as fast dissociating dopamine 2 receptor antagonists |
US8933101B2 (en) | 2007-04-23 | 2015-01-13 | Janssen Pharmaceutica Nv | Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists |
US8940743B2 (en) | 2005-10-26 | 2015-01-27 | Janssen Pharmaceutica Nv | Piperidin-4-yl-pyridazin-3-ylamine derivatives as fast dissociating dopamine 2 receptor antagonists |
WO2020223267A1 (en) * | 2019-05-01 | 2020-11-05 | Boehringer Ingelheim International Gmbh | (r)-(2-methyloxiran-2-yl)methyl 4-bromobenzenesulfonate |
EP4115885A1 (en) | 2021-07-05 | 2023-01-11 | Charité - Universitätsmedizin Berlin | A pharmaceutical composition comprising bay 86-5277 and salts thereof for use in the treatment of viral infections and hyperinflammation |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CO5300399A1 (en) | 2000-02-25 | 2003-07-31 | Astrazeneca Ab | HETEROCICLIOCS CONTAINING NITROGEN, PROCESS FOR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
US7005439B2 (en) * | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
AR035230A1 (en) * | 2001-03-19 | 2004-05-05 | Astrazeneca Ab | BENCIMIDAZOL COMPOUNDS, PROCESS FOR PREPARATION, PHARMACEUTICAL COMPOSITION, PROCESS FOR THE PREPARATION OF SUCH PHARMACEUTICAL COMPOSITION, AND USES OF THESE COMPOUNDS FOR THE PREPARATION OF MEDICINES |
WO2004072034A1 (en) * | 2003-02-17 | 2004-08-26 | F. Hoffmann-La Roche Ag | Piperidine-benzenesulfonamide derivatives |
TW200744612A (en) * | 2005-08-26 | 2007-12-16 | Astrazeneca Ab | New combination |
WO2015095265A1 (en) * | 2013-12-19 | 2015-06-25 | Merck Sharp & Dohme Corp. | Hiv protease inhibitors |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999025686A1 (en) * | 1997-11-18 | 1999-05-27 | Teijin Limited | Cyclic amine derivatives and their use as drugs |
Family Cites Families (96)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1220440B (en) | 1962-02-14 | 1966-07-07 | Sanol Arznei Schwarz Gmbh | Process for the preparation of derivatives of 1- (o-bromophenoxy) -2-hydroxy-3-aminopropane and their acid addition salts |
US3577432A (en) * | 1968-12-23 | 1971-05-04 | Robins Co Inc A H | 1-substituted-3-phenoxypyrrolidines |
US4029801A (en) | 1970-09-03 | 1977-06-14 | John Wyeth & Brother Limited | Pharmaceutical compositions and methods of treating hypertension |
JPS5511670B1 (en) | 1971-07-13 | 1980-03-26 | ||
US4080328A (en) | 1971-07-13 | 1978-03-21 | Sumitomo Chemical Company, Limited | N-substituted heterocyclic derivatives and preparation thereof |
US3994974A (en) | 1972-02-05 | 1976-11-30 | Yamanouchi Pharmaceutical Co., Ltd. | α-Aminomethylbenzyl alcohol derivatives |
US3755584A (en) * | 1972-04-03 | 1973-08-28 | Abbott Lab | Tranquilizers |
SE378109B (en) | 1972-05-19 | 1975-08-18 | Bofors Ab | |
FR2190430A1 (en) | 1972-06-29 | 1974-02-01 | Ferlux | N-aminomethylhydroxamic acids - with antiinflammatory activity pre-pared by Mannich reaction |
US3818017A (en) | 1973-01-04 | 1974-06-18 | Janssen Pharmaceutica Nv | 1-{8 1-(2-hydroxy-3-aryloxypropyl)-4-piperidyl{9 -2-benzimidazolinones and related compounds |
US3894030A (en) | 1973-01-04 | 1975-07-08 | Janssen Pharmaceutica Nv | 1-{8 1-(2-Hydroxy-3-aryloxypropyl)-4-piperidyl{9 -2-benzimidazolinones and related compounds |
US4166119A (en) * | 1978-04-14 | 1979-08-28 | American Hoechst Corporation | Analgesic and tranquilizing spiro[dihydrobenzofuran]piperidines and pyrrolidines |
WO1980000152A1 (en) | 1978-07-03 | 1980-02-07 | Sandoz Ag | 3-aminopropoxy-aryl derivates,preparation and use thereof |
US4264613A (en) | 1979-08-01 | 1981-04-28 | Science Union Et Cie, Societe Francaise De Recherche Medicale | Piperidylbenzimidazolinone compounds |
FR2469411A1 (en) | 1979-11-15 | 1981-05-22 | Science Union & Cie | NOVEL PIPERIDYLBENZIMIDAZOLINONE DERIVATIVES, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
EP0095454A3 (en) | 1982-05-13 | 1985-04-03 | Gerot-Pharmazeutika Gesellschaft m.b.H. | Nuclens-substituted pyrogallol derivatives |
JPS59222484A (en) | 1983-06-02 | 1984-12-14 | Kowa Co | Tetrahydronaphthylcarboxylic acid phenyl ester derivative |
GB8334494D0 (en) | 1983-12-24 | 1984-02-01 | Tanabe Seiyaku Co | Carbostyril derivatives |
US5614533A (en) * | 1987-03-13 | 1997-03-25 | Bio-Mega/Boehringer Ingelheim Research, Inc. | Substituted pipecolinic acid derivatives as HIV protease inhibitors |
DE3723568C2 (en) | 1987-07-16 | 1994-01-27 | Siemens Ag | Residual current circuit breaker |
DE3723648A1 (en) | 1987-07-17 | 1989-01-26 | Sandoz Ag | Indole derivatives, their preparation and medicaments containing them |
AU4414289A (en) * | 1988-09-30 | 1990-04-18 | Mallinckrodt, Inc. | A process for the production of granular metal soaps |
GR1001529B (en) | 1990-09-07 | 1994-03-31 | Elmuquimica Farm Sl | Process for the obtainment of a new pregna-1,4-diene-3,20-dione -16-17-acetal-21 esters |
SE9003057D0 (en) | 1990-09-26 | 1990-09-26 | Astra Ab | NEW PROCESS |
ES2027897A6 (en) | 1991-01-24 | 1992-06-16 | Espanola Prod Quimicos | Diphenylmethylpiperazine derivatives. |
IL105716A0 (en) | 1992-06-08 | 1993-09-22 | Richter Gedeon Vegyeszet | Aminopropanol derivatives,their preparation and pharmaceutical compositions containing them |
FI933472A (en) | 1992-08-07 | 1994-02-08 | Sankyo Co | Peptides for the production of inhibitory effects in HIV proteas, for the development and therapeutic use of HIV |
US5741789A (en) * | 1995-01-17 | 1998-04-21 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
US5614523A (en) * | 1995-01-17 | 1997-03-25 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
US5789402A (en) * | 1995-01-17 | 1998-08-04 | Eli Lilly Company | Compounds having effects on serotonin-related systems |
US5576321A (en) * | 1995-01-17 | 1996-11-19 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
US5627196A (en) * | 1995-01-17 | 1997-05-06 | Eli Lilly And Company | Compounds having effects on serotonin-related systems |
GB9624482D0 (en) | 1995-12-18 | 1997-01-15 | Zeneca Phaema S A | Chemical compounds |
ZA9610738B (en) | 1995-12-22 | 1997-06-24 | Warner Lambert Co | Subtype selective nmda receptor ligands and the use thereof |
IL125686A (en) | 1996-02-13 | 2002-11-10 | Zeneca Ltd | Quinazoline derivatives, processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament having an antiangiogenic and/or vascular permeability reducing effect |
WO1997032856A1 (en) | 1996-03-05 | 1997-09-12 | Zeneca Limited | 4-anilinoquinazoline derivatives |
GB9718972D0 (en) | 1996-09-25 | 1997-11-12 | Zeneca Ltd | Chemical compounds |
DE19703131A1 (en) | 1997-01-29 | 1998-07-30 | Bayer Ag | Use of quinoxaline in a combination of three with protease inhibitors and reverse transcriptase inhibitors as medicaments for the treatment of AIDS and / or HIV infections |
GB9714249D0 (en) | 1997-07-08 | 1997-09-10 | Angiogene Pharm Ltd | Vascular damaging agents |
IL125658A0 (en) | 1997-08-18 | 1999-04-11 | Hoffmann La Roche | Ccr-3 receptor antagonists |
DE19755268A1 (en) | 1997-12-12 | 1999-06-17 | Merck Patent Gmbh | Benzamidine derivatives |
FR2780057B1 (en) | 1998-06-18 | 2002-09-13 | Sanofi Sa | PHENOXYPROPANOLAMINES, PROCESS FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
BR9915735A (en) | 1998-11-20 | 2001-09-04 | Hoffmann La Roche | Piperidine ccr-3 receptor antagonists |
WO2000035451A1 (en) | 1998-12-18 | 2000-06-22 | Du Pont Pharmaceuticals Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
EP1156807A4 (en) | 1998-12-18 | 2002-04-03 | Du Pont Pharm Co | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
GB9900334D0 (en) | 1999-01-07 | 1999-02-24 | Angiogene Pharm Ltd | Tricylic vascular damaging agents |
GB9900752D0 (en) | 1999-01-15 | 1999-03-03 | Angiogene Pharm Ltd | Benzimidazole vascular damaging agents |
SE9900833D0 (en) | 1999-03-09 | 1999-03-09 | Astra Ab | Novel combination |
WO2000053600A1 (en) | 1999-03-11 | 2000-09-14 | Banyu Pharmaceutical Co., Ltd. | Novel piperidine derivatives |
JP2002540204A (en) | 1999-03-26 | 2002-11-26 | アストラゼネカ・アクチエボラーグ | New compound |
JP3495955B2 (en) * | 1999-03-26 | 2004-02-09 | シャープ株式会社 | Semiconductor memory device and method of manufacturing the same |
GB9913083D0 (en) | 1999-06-04 | 1999-08-04 | Novartis Ag | Organic compounds |
JP2004506593A (en) | 1999-05-14 | 2004-03-04 | コンビケム インコーポレイテッド | Cyclic amine derivatives and their uses |
ES2165768B1 (en) | 1999-07-14 | 2003-04-01 | Almirall Prodesfarma Sa | NEW DERIVATIVES OF QUINUCLIDINE AND PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM. |
AUPQ165599A0 (en) | 1999-07-15 | 1999-08-05 | University Of Sydney, The | Optical processing method and apparatus and products thereof |
SE9902987D0 (en) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
FR2802533B1 (en) | 1999-12-17 | 2002-02-15 | Sanofi Synthelabo | PHENOXYPROPANOLAMINES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
ATE356624T1 (en) | 1999-12-17 | 2007-04-15 | Sanofi Aventis | PHENOXYPROPANOLAMINE DERIVATIVES, THEIR PREPARATION AND THERAPEUTIC USE |
CO5300399A1 (en) | 2000-02-25 | 2003-07-31 | Astrazeneca Ab | HETEROCICLIOCS CONTAINING NITROGEN, PROCESS FOR PREPARATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM |
GB0011838D0 (en) | 2000-05-17 | 2000-07-05 | Astrazeneca Ab | Chemical compounds |
GB0012260D0 (en) | 2000-05-19 | 2000-07-12 | Astrazeneca Ab | Novel composition |
IL152682A0 (en) | 2000-05-31 | 2003-06-24 | Astrazeneca Ab | Indole derivatives with vascular damaging activity |
US7005439B2 (en) | 2000-06-20 | 2006-02-28 | Astrazeneca Ab | Compounds |
AR028947A1 (en) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | NEW COMPOUNDS |
AR028948A1 (en) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | NEW COMPOUNDS |
EP1294690A2 (en) | 2000-06-21 | 2003-03-26 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
GB0015876D0 (en) | 2000-06-28 | 2000-08-23 | Novartis Ag | Organic compounds |
WO2002004434A1 (en) | 2000-07-07 | 2002-01-17 | Angiogene Pharmaceuticals Limited | Colchinol derivatives as vascular damaging agents |
RU2003103603A (en) | 2000-07-07 | 2004-08-20 | Энджиоджен Фармасьютикалз Лимитед (Gb) | Derivatives of colchinol as inhibitors of angiogenesis |
AR032471A1 (en) | 2000-08-05 | 2003-11-12 | Glaxo Group Ltd | DERIVED FROM ANDROSTAN AND SOLVATOS OF THE SAME, ITS USE FOR THE MANUFACTURE OF MEDICINES, PHARMACEUTICAL COMPOSITIONS THAT INCLUDE THEM, PROCESSES TO PREPARE SUCH DERIVATIVES, USEFUL INTERMEDIARIES IN THE PREPARATION OF SUCH DERIVATIVES, PROCESSES TO PREPARE SUCH INTERMEDIATES |
GB0021670D0 (en) | 2000-09-04 | 2000-10-18 | Astrazeneca Ab | Chemical compounds |
GB0029562D0 (en) | 2000-12-04 | 2001-01-17 | Novartis Ag | Organic compounds |
GB2373186A (en) | 2001-02-23 | 2002-09-18 | Astrazeneca Ab | Pharmaceutical combinations of a CCR3 antagonist and a compound which is usefulreatment of asthma, allergic disease or inflammation |
AR035230A1 (en) | 2001-03-19 | 2004-05-05 | Astrazeneca Ab | BENCIMIDAZOL COMPOUNDS, PROCESS FOR PREPARATION, PHARMACEUTICAL COMPOSITION, PROCESS FOR THE PREPARATION OF SUCH PHARMACEUTICAL COMPOSITION, AND USES OF THESE COMPOUNDS FOR THE PREPARATION OF MEDICINES |
ATE381537T1 (en) | 2001-03-22 | 2008-01-15 | Glaxo Group Ltd | FORMANILIDE DERIVATIVES AS BETA2 ADRENORECEPTOR AGONISTS |
GB0107228D0 (en) | 2001-03-22 | 2001-05-16 | Astrazeneca Ab | Chemical compounds |
SE0101038D0 (en) | 2001-03-23 | 2001-03-23 | Astrazeneca Ab | Novel compounds |
KR100406536B1 (en) * | 2001-03-28 | 2003-11-20 | 주식회사 하이닉스반도체 | FeRAM having aluminum oxide layer as oxygen diffusion barrier and method for forming the same |
GB0108046D0 (en) | 2001-03-30 | 2001-05-23 | Astrazeneca Ab | Chemical compounds |
JP4261914B2 (en) | 2001-04-27 | 2009-05-13 | 田辺三菱製薬株式会社 | New benzylpiperidine compounds |
CA2445839A1 (en) | 2001-04-30 | 2002-11-07 | Glaxo Group Limited | Anti-inflammatory 17.beta.-carbothioate ester derivatives of androstane with a cyclic ester group in position 17.alpha |
CN1290194C (en) * | 2001-06-25 | 2006-12-13 | 松下电器产业株式会社 | Capacitance element, semiconductor storage and preparing method thereof |
US6818935B2 (en) * | 2001-09-12 | 2004-11-16 | Hynix Semiconductor Inc. | Semiconductor device and method for fabricating the same |
TWI249515B (en) | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
GB0127547D0 (en) | 2001-11-16 | 2002-01-09 | Astrazeneca Ab | Chemical compounds |
SE0104251D0 (en) | 2001-12-14 | 2001-12-14 | Astrazeneca Ab | Novel compounds |
TW200303304A (en) | 2002-02-18 | 2003-09-01 | Astrazeneca Ab | Chemical compounds |
SE0200919D0 (en) | 2002-03-25 | 2002-03-25 | Astrazeneca Ab | Chemical compounds |
GB0207436D0 (en) | 2002-03-28 | 2002-05-08 | Glaxo Group Ltd | Novel compounds |
US6583507B1 (en) * | 2002-04-26 | 2003-06-24 | Bum Ki Moon | Barrier for capacitor over plug structures |
AU2003269316A1 (en) | 2002-10-11 | 2004-05-04 | Pfizer Inc. | Indole derivatives as beta-2 agonists |
KR100578212B1 (en) * | 2003-06-30 | 2006-05-11 | 주식회사 하이닉스반도체 | Capacitor with merged top electrode plate line structure and method for fabricating the same |
US7180141B2 (en) * | 2004-12-03 | 2007-02-20 | Texas Instruments Incorporated | Ferroelectric capacitor with parallel resistance for ferroelectric memory |
EP1912942A1 (en) | 2005-08-01 | 2008-04-23 | AstraZeneca AB | Novel piperidine derivatives as chemokine receptor modulators useful for the treatment of respiratory diseases. |
TW200738634A (en) | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
TW200734305A (en) | 2005-08-02 | 2007-09-16 | Astrazeneca Ab | New salt III |
-
2001
- 2001-06-11 AR ARP010102758A patent/AR028948A1/en unknown
- 2001-06-14 US US10/311,841 patent/US6911458B2/en not_active Expired - Fee Related
- 2001-06-14 JP JP2002504229A patent/JP4022142B2/en not_active Expired - Lifetime
- 2001-06-14 MX MXPA02012425A patent/MXPA02012425A/en active IP Right Grant
- 2001-06-14 RU RU2006141320/04A patent/RU2419608C2/en not_active IP Right Cessation
- 2001-06-14 CZ CZ20024146A patent/CZ20024146A3/en unknown
- 2001-06-14 AU AU7476301A patent/AU7476301A/en active Pending
- 2001-06-14 EP EP01941406A patent/EP1299357A1/en not_active Withdrawn
- 2001-06-14 PL PL366198A patent/PL203936B1/en not_active IP Right Cessation
- 2001-06-14 NZ NZ523047A patent/NZ523047A/en unknown
- 2001-06-14 CA CA002414095A patent/CA2414095C/en not_active Expired - Fee Related
- 2001-06-14 HU HU0301187A patent/HUP0301187A3/en unknown
- 2001-06-14 SK SK1793-2002A patent/SK17932002A3/en not_active Application Discontinuation
- 2001-06-14 BR BR0111667-3A patent/BR0111667A/en not_active Application Discontinuation
- 2001-06-14 IL IL15316701A patent/IL153167A0/en unknown
- 2001-06-14 EE EEP200200704A patent/EE05157B1/en not_active IP Right Cessation
- 2001-06-14 CN CNB018142141A patent/CN1307157C/en not_active Expired - Fee Related
- 2001-06-14 AU AU2001274763A patent/AU2001274763B2/en not_active Ceased
- 2001-06-14 RU RU2002132385/04A patent/RU2298550C2/en not_active IP Right Cessation
- 2001-06-14 WO PCT/SE2001/001377 patent/WO2001098273A1/en active IP Right Grant
- 2001-06-14 KR KR1020027017281A patent/KR100799061B1/en not_active IP Right Cessation
- 2001-06-18 MY MYPI20012866A patent/MY136520A/en unknown
-
2002
- 2002-11-28 IL IL153167A patent/IL153167A/en not_active IP Right Cessation
- 2002-12-17 NO NO20026064A patent/NO324698B1/en not_active IP Right Cessation
- 2002-12-17 IS IS6658A patent/IS6658A/en unknown
-
2004
- 2004-11-22 US US10/994,683 patent/US7528156B2/en not_active Expired - Fee Related
-
2009
- 2009-05-04 US US12/434,955 patent/US20090306141A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999025686A1 (en) * | 1997-11-18 | 1999-05-27 | Teijin Limited | Cyclic amine derivatives and their use as drugs |
Cited By (55)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7528156B2 (en) | 2000-06-20 | 2009-05-05 | Astrazeneca Ab | Compounds |
US7449475B2 (en) | 2002-07-08 | 2008-11-11 | Astrazeneca Ab | Tricyclic spiropiperidines or spiropyrrolidines |
US9476045B2 (en) | 2003-04-17 | 2016-10-25 | Alnylam Pharmaceuticals, Inc. | iRNA agents with biocleavable tethers |
US8426377B2 (en) | 2003-04-17 | 2013-04-23 | Alnylam Pharmaceuticals, Inc. | iRNA agents with biocleavable tethers |
US8344125B2 (en) | 2003-04-17 | 2013-01-01 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US9394540B2 (en) | 2003-04-17 | 2016-07-19 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US8507661B2 (en) | 2003-04-17 | 2013-08-13 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US8017762B2 (en) | 2003-04-17 | 2011-09-13 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US10119138B2 (en) | 2003-04-17 | 2018-11-06 | Alnylam Pharmaceuticals, Inc. | iRNA agents with biocleavable tethers |
US10676740B2 (en) | 2003-04-17 | 2020-06-09 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US7851615B2 (en) | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
US11312957B2 (en) | 2003-04-17 | 2022-04-26 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US11015194B2 (en) | 2003-04-17 | 2021-05-25 | Alnylam Pharmaceuticals, Inc. | iRNA agents with biocleavable tethers |
US8865677B2 (en) | 2003-04-17 | 2014-10-21 | Alnylam Pharmaceuticals, Inc. | iRNA agents with biocleavable tethers |
US8796436B2 (en) | 2003-04-17 | 2014-08-05 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
US7732442B2 (en) | 2003-09-05 | 2010-06-08 | Ono Pharmaceutical Co., Ltd. | Chemokine receptor antagonist and medical use thereof |
WO2005023771A1 (en) * | 2003-09-05 | 2005-03-17 | Ono Pharmaceutical Co., Ltd. | Chemokine receptor antagonist and medical use thereof |
JPWO2005023771A1 (en) * | 2003-09-05 | 2006-11-02 | 小野薬品工業株式会社 | Chemokine receptor antagonist and its pharmaceutical use |
US7498338B2 (en) | 2003-11-20 | 2009-03-03 | Astrazeneca Ab | Compounds |
US7524856B2 (en) | 2003-12-22 | 2009-04-28 | Astrazeneca Ab | Tricyclic spiroderivatives as modulators of chemokine receptor activity |
WO2007015664A1 (en) * | 2005-08-01 | 2007-02-08 | Astrazeneca Ab | Novel piperidine derivatives as chemokine receptor modulators useful for the treatment of respiratory diseases. |
WO2007015667A1 (en) * | 2005-08-02 | 2007-02-08 | Astrazeneca Ab | New salt ii |
WO2007015666A1 (en) * | 2005-08-02 | 2007-02-08 | Astrazeneca Ab | New salt i |
US8148405B2 (en) | 2005-08-02 | 2012-04-03 | Astrazeneca Ab | Salt I |
WO2007015668A1 (en) * | 2005-08-02 | 2007-02-08 | Astrazeneca Ab | New salt iii |
US9751860B2 (en) | 2005-10-26 | 2017-09-05 | Janssen Pharmaceutica Nv | Piperidin-4YL-pyridazin-3-ylamine derivatives as fast dissociating dopamine 2 receptor antagonists |
US9468640B2 (en) | 2005-10-26 | 2016-10-18 | Janssen Pharmaceutica Nv | Piperidin-4-yl-pyridazin-3-ylamine derivatives as fast dissociating dopamine 2 receptor antagonists |
US8940743B2 (en) | 2005-10-26 | 2015-01-27 | Janssen Pharmaceutica Nv | Piperidin-4-yl-pyridazin-3-ylamine derivatives as fast dissociating dopamine 2 receptor antagonists |
WO2007053082A1 (en) * | 2005-11-02 | 2007-05-10 | Astrazeneca Ab | Novel 1 -benzyl-4-piperidinamines that are useful in the treatment of copd and asthma |
WO2007102767A1 (en) * | 2006-03-07 | 2007-09-13 | Astrazeneca Ab | Piperidine derivatives, their process for preparation, their use as therapeutic agents and pharmaceutical compositions containing them |
WO2007102768A1 (en) * | 2006-03-07 | 2007-09-13 | Astrazeneca Ab | Piperidine derivatives, their process for preparation, their use as therapeutic agents and pharmaceutical compositions containing them . |
EP2027105A4 (en) * | 2006-05-10 | 2011-04-13 | Astrazeneca Ab | Novel process for preparing intermediates of ccr antagonists |
EP2027105A2 (en) * | 2006-05-10 | 2009-02-25 | AstraZeneca AB | Novel process for preparing intermediates of ccr antagonists |
WO2008010764A3 (en) * | 2006-07-18 | 2008-03-13 | Astrazeneca Ab | A process for the preparation of substituted 2-acetylamino-alkoxyphenyl |
WO2008010764A2 (en) * | 2006-07-18 | 2008-01-24 | Astrazeneca Ab | A process for the preparation of substituted 2-acetylamino-alkoxyphenyl |
US8466153B2 (en) | 2006-12-08 | 2013-06-18 | Janssen Pharmaceutica N.V. | Piperidinylamino-pyridazines and their use as fast dissociating dopamine 2 receptor antagonists |
EP2364704A1 (en) | 2007-02-08 | 2011-09-14 | AstraZeneca AB | Combination of beta-adrenoceptor agonist and corticosteroid |
US9422296B2 (en) | 2007-02-13 | 2016-08-23 | Janssen Pharmaceutica Nv | Fast-dissociating dopamine 2 receptor antagonists |
US8791120B2 (en) | 2007-02-13 | 2014-07-29 | Janssen Pharmaceutica Nv | Fast-dissociating dopamine 2 receptor antagonists |
WO2008103125A1 (en) * | 2007-02-23 | 2008-08-28 | Astrazeneca Ab | Novel combination of compounds to be used in the treatment of airway diseases, especially chronic obstructive pulmonary disease (copd) and asthma |
WO2008121065A1 (en) * | 2007-03-30 | 2008-10-09 | Astrazeneca Ab | Novel pyrrolidine derivatives as antagonists of the chemokine receptor |
US8906921B2 (en) | 2007-04-23 | 2014-12-09 | Janssen Pharmaceutica Nv | 4-alkoxypyridazine derivatives as fast dissociating dopamine 2 receptor antagonists |
US8933101B2 (en) | 2007-04-23 | 2015-01-13 | Janssen Pharmaceutica Nv | Thia(dia)zoles as fast dissociating dopamine 2 receptor antagonists |
US8530474B2 (en) | 2008-07-03 | 2013-09-10 | Janssen Pharmaceutica Nv | Substituted 6-(1-piperazinyl)-pyridazines as 5-HT6 receptor antagonists |
US8895562B2 (en) | 2008-07-31 | 2014-11-25 | Janssen Pharmaceutica Nv | Piperazin-1-yl-trifluoromethyl-substituted-pyridines as fast dissociating dopamine 2 receptor antagonists |
WO2011012897A1 (en) | 2009-07-31 | 2011-02-03 | Astrazeneca Ab | New combinations for the treatment of asthma |
WO2011061527A1 (en) | 2009-11-17 | 2011-05-26 | Astrazeneca Ab | Combinations comprising a glucocorticoid receptor modulator for the treatment of respiratory diseases |
WO2011073662A1 (en) | 2009-12-17 | 2011-06-23 | Astrazeneca Ab | Combination of a benzoxazinone and a further agent for treating respiratory diseases |
WO2012085583A1 (en) | 2010-12-23 | 2012-06-28 | Astrazeneca Ab | New compound |
WO2012085582A1 (en) | 2010-12-23 | 2012-06-28 | Astrazeneca Ab | Compound |
WO2012163848A1 (en) | 2011-05-27 | 2012-12-06 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for the treatment of crohn's disease |
WO2020223267A1 (en) * | 2019-05-01 | 2020-11-05 | Boehringer Ingelheim International Gmbh | (r)-(2-methyloxiran-2-yl)methyl 4-bromobenzenesulfonate |
US11958818B2 (en) | 2019-05-01 | 2024-04-16 | Boehringer Ingelheim International Gmbh | (R)-(2-methyloxiran-2-yl)methyl 4-bromobenzenesulfonate |
EP4115885A1 (en) | 2021-07-05 | 2023-01-11 | Charité - Universitätsmedizin Berlin | A pharmaceutical composition comprising bay 86-5277 and salts thereof for use in the treatment of viral infections and hyperinflammation |
WO2023280828A1 (en) | 2021-07-05 | 2023-01-12 | Charité - Universitätsmedizin Berlin | A pharmaceutical composition comprising bay 86-5277 and salts thereof for use in the treatment of viral infections and hyperinflammation |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6911458B2 (en) | Compounds | |
AU2001274763A1 (en) | Novel compounds | |
US7345063B2 (en) | Amides, preparation and therapeutic use as modulators of CCR-receptor activity | |
US7186718B2 (en) | Piperidinyl-morpholinyl derivatives as modulators of chemokine receptor activity | |
US20040116435A1 (en) | Benzimidazol derivatives modulate chemokine receptors | |
EP1299356B1 (en) | Novel compounds | |
EP1421070B1 (en) | New piperidinyl derivates as modulators of chemokine receptor activity | |
US7005439B2 (en) | Compounds | |
AU2001274764B2 (en) | Novel compounds | |
ZA200209904B (en) | Novel compounds. | |
AU2001274764A1 (en) | Novel compounds | |
AU2002243154A1 (en) | Novel amides, preparation and therapeutic use as modulators of CCR-receptor activity | |
ZA200209906B (en) | Novel compounds. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2001274763 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 153167 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2414095 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: IN/PCT/2002/01718/MU Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002/09904 Country of ref document: ZA Ref document number: 200209904 Country of ref document: ZA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 523047 Country of ref document: NZ |
|
ENP | Entry into the national phase |
Ref document number: 2002 504229 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/A/2002/012425 Country of ref document: MX |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2001941406 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: PV2002-4146 Country of ref document: CZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 17932002 Country of ref document: SK Ref document number: 1020027017281 Country of ref document: KR |
|
ENP | Entry into the national phase |
Ref document number: 2002132385 Country of ref document: RU Kind code of ref document: A Ref country code: RU Ref document number: RU A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 018142141 Country of ref document: CN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 10311841 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 1020027017281 Country of ref document: KR |
|
WWP | Wipo information: published in national office |
Ref document number: 2001941406 Country of ref document: EP |
|
REG | Reference to national code |
Ref country code: DE Ref legal event code: 8642 |
|
WWP | Wipo information: published in national office |
Ref document number: PV2002-4146 Country of ref document: CZ |
|
WWP | Wipo information: published in national office |
Ref document number: 523047 Country of ref document: NZ |
|
WWG | Wipo information: grant in national office |
Ref document number: 523047 Country of ref document: NZ |