WO2000039077A2 - Thyroid receptor ligands - Google Patents
Thyroid receptor ligands Download PDFInfo
- Publication number
- WO2000039077A2 WO2000039077A2 PCT/IB1999/002084 IB9902084W WO0039077A2 WO 2000039077 A2 WO2000039077 A2 WO 2000039077A2 IB 9902084 W IB9902084 W IB 9902084W WO 0039077 A2 WO0039077 A2 WO 0039077A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- hydroxy
- isopropylphenoxy
- dibromo
- benzoyl
- phenylacetyl
- Prior art date
Links
- 0 CC(C)[C@@](*)NC(Cc(cc1Br)cc(Br)c1Oc(cc1)cc(C(C)C)c1O)=O Chemical compound CC(C)[C@@](*)NC(Cc(cc1Br)cc(Br)c1Oc(cc1)cc(C(C)C)c1O)=O 0.000 description 3
- FGVPCGSDRQMLTB-UHFFFAOYSA-N CNCCC1N(C)CCC1 Chemical compound CNCCC1N(C)CCC1 FGVPCGSDRQMLTB-UHFFFAOYSA-N 0.000 description 1
- UKYSWWLKULEJFA-UHFFFAOYSA-N CNCCCN1CCOCC1 Chemical compound CNCCCN1CCOCC1 UKYSWWLKULEJFA-UHFFFAOYSA-N 0.000 description 1
- KCAUHAHOMIRXAN-UHFFFAOYSA-N CNCCN1CCCCC1 Chemical compound CNCCN1CCCCC1 KCAUHAHOMIRXAN-UHFFFAOYSA-N 0.000 description 1
- HDSZRJMNBCRATE-UHFFFAOYSA-N CNCCN1CCNCC1 Chemical compound CNCCN1CCNCC1 HDSZRJMNBCRATE-UHFFFAOYSA-N 0.000 description 1
- COCFQAQFBIRRKQ-UHFFFAOYSA-N CNCCNc1ccccc1 Chemical compound CNCCNc1ccccc1 COCFQAQFBIRRKQ-UHFFFAOYSA-N 0.000 description 1
- PHSPJQZRQAJPPF-UHFFFAOYSA-N CNCCc1cnc[nH]1 Chemical compound CNCCc1cnc[nH]1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
- C07D207/24—Oxygen or sulfur atoms
- C07D207/26—2-Pyrrolidones
- C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
- C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
- A61P5/16—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4 for decreasing, blocking or antagonising the activity of the thyroid hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/32—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/42—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/44—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring
- C07C235/52—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton with carbon atoms of carboxamide groups and singly-bound oxygen atoms bound to carbon atoms of the same non-condensed six-membered aromatic ring having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C307/04—Diamides of sulfuric acids
- C07C307/06—Diamides of sulfuric acids having nitrogen atoms of the sulfamide groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
- C07C311/51—Y being a hydrogen or a carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C323/39—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
- C07C323/40—Y being a hydrogen or a carbon atom
- C07C323/41—Y being a hydrogen or an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/60—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton with the carbon atom of at least one of the carboxyl groups bound to nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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
- C07D207/08—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom 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 hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
- C07D207/09—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
-
- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/24—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by sulfur atoms to which a second hetero atom is attached
-
- 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
- C07D211/08—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/34—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 hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/92—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with a hetero atom directly attached to the ring nitrogen atom
- C07D211/96—Sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/40—Acylated substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D223/00—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom
- C07D223/02—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings 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
- C07D223/12—Nitrogen atoms not forming part of a nitro radical
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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
- C07D231/38—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/06—1,2,3-Thiadiazoles; Hydrogenated 1,2,3-thiadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/04—Thiadiazoles; Hydrogenated thiadiazoles not condensed with other rings
- C07D285/12—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles
- C07D285/125—1,3,4-Thiadiazoles; Hydrogenated 1,3,4-thiadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
- C07D285/135—Nitrogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/125—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/13—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
Definitions
- This invention relates to novel compounds which are thyroid receptor ligands. and are preferably selective for the thyroid hormone receptor ⁇ , to methods of preparing such compounds and to methods for using such compounds such as in the regulation of metabolism.
- Thyroid hormones affect the metabolism of virtually every cell of the body. At normal levels, these hormones maintain body weight, the metabolic rate, body temperature. and mood, and influence serum low density lipoprotein (LDL) levels. Thus, in hypothyroidism there is weight gain, high levels of LDL cholesterol, and depression. In excess with hyperthyroidism. these hormones lead to weight loss, hypermetabolism. lowering of serum LDL levels, cardiac arrhythmias, heart failure, muscle weakness, bone loss in postmenopausal women, and anxiety. Thyroid hormones are currently used primarily as replacement therapy for patients with hypothyroidism. Therapy with L-thyroxine returns metabolic functions to normal and can easily be monitored with routine serum measurements of levels of thyroid-stimulating hormone (TSH).
- TSH thyroid-stimulating hormone
- thyroxine (3.5.3'.5'-tetraiodo-L-thyronine. or T 4 ) and triiodothyronine (3,5.3'-triiodo-L-thyronine. or T ? ).
- T 4 triiodothyronine
- T ? triiodothyronine
- thyroid hormones may be therapeutically useful in non-thyroid disorders if adverse effects can be minimized or eliminated.
- These potentially useful influences include weight reduction, lowering of serum LDL levels, amelioration of depression and stimulation of bone formation.
- Prior attempts to utilize thyroid hormones pharmacologically to treat these disorders have been limited by manifestations of hyperthyroidism. and in particular by cardiovascular toxicity.
- Tissue-selective thyroid hormone agonists may be obtained by selective tissue uptake or extrusion, topical or local delivery, targeting to cells through other ligands attached to the agonist and targeting receptor subtypes.
- Thyroid hormone receptor agonists that interact selectively with the ⁇ -form of the thyroid hormone receptor offers an especially attractive method for avoiding cardio-toxicity.
- TRs Thyroid hormone receptors
- the various receptor forms appear to be products of two different genes ⁇ and ⁇ . Further isoform differences are due to the fact that differential RNA processing results in at least two isoforms from each gene.
- the TR ⁇ i, TR ⁇ i and TR ⁇ 2 isoforms bind thyroid hormone and act as ligand-regulated transcription factors. In adults, the TR ⁇ i isoform is the most prevalent form in most tissues, especially in the liver and muscle.
- the TR ⁇ 2 isoform is prevalent in the pituitary and other parts of the central nervous system, does not bind thyroid hormones, and acts in many contexts as a transcriptional repressor.
- TR i isoform is also widely distributed, although its levels are generally lower than those of the TR ⁇ i isoform. This isoform may be especially important for development. Whereas many mutations in the TR ⁇ gene have been found and lead to the syndrome of generalized resistance to thyroid hormone, mutations leading to impaired TR ⁇ function have not been found.
- tachycardia is very common in the syndrome of generalized resistance to thyroid hormone in which there are defective TR ⁇ -forms, and high circulating levels of T 4 and T 3 ; 2) there was a tachycardia in the only described patient with a double deletion of the
- TR ⁇ gene Takeda et al, J. Clin. Endrocrinol. & Metab. 1992, Vol. 74, p. 49;
- a TR ⁇ -selective agonist could be used to mimic a number of thyroid hormone actions, while having a lesser effect on the heart.
- Such a compound may be used for: (1) replacement therapy in elderly subjects with hypothyroidism who are at risk for cardiovascular complications; (2) replacement therapy in elderly subjects with subclinical hypothyroidism who are at risk for cardiovascular complications; (3) obesity; (4) hypercholesterolemia due to - j -
- n is an integer from 0 to 4;
- Ri is halogen, trifluoromethyl, or alkyl of 1 to 6 carbons or cycloalkyl of 3 to 7 carbons;
- R 2 and Ri are the same or different and are hydrogen, halogen, alkyl of 1 to 4 carbons or cycloalkyl of 3 to 5 carbons, at least one of R and Ri being other than hydrogen; i is a heteroaromatic moiety which may be substituted or unsubstituted and is linked to (CH 2 ) n via a nitrogen atom or a carbon atom; an amine (NR'R"), including those in which the amine is derived from an alpha amino acid of either natural (L) or unnatural (D) stereochemistry; an acylsulphonamide (CONHSO 2 R') or a carboxylic acid amide (CONR'R”) in which the amine portion of the carboxylic amide can be derived from an achiral or a L or D alpha amino acid such as when the general structure -CONR'R" can be represented by
- R", R'" and R"" are the same or different and are independently selected from hydrogen, alkyl, aryl and heteroaryl, substituted or unsubstituted, and R* may be hydrogen, alkyl, aryl and heteroaryl, substituted or unsubstituted.
- a method for preventing, inhibiting or treating a disease associated with metabolism dysfunction or which is dependent upon the expression of a T 3 regulated gene wherein a compound of formula I is administered in a therapeutically effective amount.
- the compound of formula I is preferably an agonist that is preferably selective for the thyroid hormone receptor-beta.
- diseases associated with metabolism dysfunction or are dependent upon the expression of a T 3 regulated gene are set out hereinafter and include obesity, hypercholesterolemia, atherosclerosis, cardiac arrhythmias, depression, osteoporosis, hypothyroidism, goiter, thyroid cancer as well as glaucoma and congestive heart failure.
- thyroid receptor ligand as used herein is intended to cover any moiety which binds to a thyroid receptor.
- the ligand may act as an agonist, an antagonist, a partial agonist or a partial antagonist.
- aliphatic hydrocarbon(s) refers to acyclic straight or branched chain groups which include alkyl, alkenyl or alkynyl groups.
- aromatic hydrocarbon(s) as used herein refers to groups including aryl groups as defined herein.
- heteroaryl or “heteroaromatic moiety” as used herein alone or as a part of another group refers to a 5- or 6-membered aromatic ring which includes 1, 2, 3, or 4 heteroatoms. one of which must be a nitrogen atom; the other heteroatoms when present may be nitrogen, oxygen or sulfur, and such rings may be fused to another aryl or heteroaryl ring, and includes possible N-oxides.
- the heteroaryl group may optionally include 1 to 4 substituents such as aryl, alkyl, alkenyl, alkynyl, cycloalkyl, hydroxy, cyano, nitro, amino and/or carboxyl, and including the following
- lower alkyl as employed herein alone or as part of another group includes both straight and branched chain hydrocarbons, containing 1 to 12 carbons (in the case of alkyl or alk), in the normal chain, preferably 1 to 4 carbons, such as methyl, ethyl, propyl, isopropyl, butyl, t-butyl, or isobutyl, pentyl, hexyl.
- aryl refers to monocyclic and bicyclic aromatic groups containing 6 to 10 carbons in the ring portion (such as phenyl or naphthyl including 1-naphthyl and 2-naphthyl) and may be optionally substituted through available carbon atoms with 1, 2, or 3 groups selected from hydrogen, halo, alkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, trifluoromethyl, trifluoromethoxy, alkynyl, hydroxy, amino, nitro. cyano and carboxylic acids.
- lower alkenyl or “alkenyl” as used herein by itself or as part of another group refers to straight or branched chain radicals of 2 to 12 carbons, preferably 2 to 5 carbons, in the normal chain, which include one to six double bonds in the normal chain, such as vinyl, 2-propenyl, 3-butenyl, 2-butenyl, 4-pentenyl, 3-pentenyl, 2-hexenyl, 3-hexenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 3-octenyl, 3-nonenyl, 4-decenyl, 3-undecenyl. 4-dodecenyl, and the like, which may be substituted as in the case of "alkyl".
- lower alkynyl or “alkynyl” as used herein by itself or as part of another group refers to straight or branched chain radicals of 2 to 12 carbons, preferably 2 to 8 carbons, in the normal chain, which include one triple bond in the normal chain, such as 2-propynyl. 3-butynyl, 2-butynyl, 4-pentynyl. 3-pentynyl, 2-hexynyl, 3-hexynyl, 2-heptynyl, 3-heptynyl.
- cycloalkyl as employed herein alone or as part of another group includes saturated cyclic hydrocarbon groups or partially unsaturated (containing 1 or 2 double bonds) cyclic hydrocarbon groups, containing one ring and a total of 3 to 7 carbons, preferably 3 to 5 carbons, forming the ring, which includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl and cyclohexenyl, , which may be substituted as in the case of "alkyl".
- halogen or "halo” as used herein alone or as part of another group refers to chlorine, bromine, fluorine, and iodine as well as CF 3 , with chlorine or bromine being preferred.
- the compounds of formula I can be present as salts, in particular pharmaceutically acceptable salts. If the compounds of formula I have, for example, at least one basic center, they can form acid addition salts.
- acetic acid such as saturated or unsaturated dicarboxylic acids, for example oxalic, malonic, succinic, maleic, fumaric, phthalic or terephthalic acid, such as hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid, such as amino acids, (for example aspartic or glutamic acid or lysine or arginine), or benzoic acid, or with organic sulfonic acids, such as (C ⁇ -C 4 ) alkyl or arylsulfonic acids which are unsubstituted or substituted, for example by halogen, for example acetic acid, such as saturated or unsaturated dicarboxylic acids, for example oxalic, malonic, succinic, maleic, fumaric, phthalic or terephthalic acid, such as hydroxycarboxylic acids, for example ascorbic, glycolic, lactic, malic, tartaric or citric acid
- Corresponding acid addition salts can also be formed having, if desired, an additionally present basic center.
- the compounds of formula I having at least one acid group can also form salts with bases.
- Suitable salts with bases are. for example, metal salts, such as alkali metal or alkaline earth metal salts, for example sodium, potassium or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, thiomorpholine, piperidine, pyrrolidine, a mono, di or trilower alkylamine, for example ethyl, tertbutyl, diethyl, diisopropyl, triethyl.
- tributyl or dimethyl-propylamine or a mono, di or trihydroxy lower alkylamine, for example mono, di or triethanolamine.
- Corresponding internal salts may furthermore be formed. Salts which are unsuitable for pharmaceutical uses but which can be employed, for example, for the isolation or purification of free compounds I or their pharmaceutically acceptable salts, are also included.
- Preferred salts of the compounds of formula I which include a basic groups include monohydrochloride. hydrogensulfate, methanesulfonate, phosphate or nitrate.
- Preferred salts of the compounds of formula I which include an acid group include sodium, potassium and magnesium salts and pharmaceutically acceptable organic amines.
- R 2 and R are independently halogen such as bromo or chloro; or R 2 and Ri are each methyl or one is methyl and the other is ethyl; or one of R and Ri is halogen such as bromo or chloro, and the other is alkyl such as methyl, or hydrogen; and n is 0. 1 or 2;
- R4 is carboxylic acid derivative of the type: amides, acylsulphonamides or an amide formed from an amino acid residue;
- R 5 is hydrogen.
- the most preferred compounds have the structures:
- Ri isopropyl, methyl, ethyl, tertiary-butyl, cyclopentyl, cyclohexyl;
- R 2 and R may be independently selected from Br, Cl and Me;
- R* may be hydrogen, alkyl, cycloalkyl, aryl and heteroaryl; * denotes either D or L stereochemistry;
- prodrug esters are described in standard references such as Chapter 31, written by Camille G. Wermuth et al., in "The Practice of Medicinal Chemistry", ed. C. G. Wermuth. Academic Press, 1996 (and the references contained therein).
- the compounds of formula I may be prepared by the exemplary processes described in the following reaction schemes. Exemplary reagents and procedures for these reactions appear hereinafter and in the working Examples.
- Scheme 1 also outlines the preparation of the intermediate iodide 5, the sequence similar to what is employed in: "Novel Thyroid Receptor Ligands and Methods. Li. Yi-Lin: Liu, Ye; Hedfors, Asa; Malm, Johan; Mellin, Charlotta; Zhang, Minsheng. PCT Int. Appl., 40 pp. CODEN: PIXXD2. WO 9900353 Al 990107". An anisole-derived iodonium salt 2 and copper bronze in an inert solvent such as dichloromethane are mixed at room temperature.
- the carboxylic acid ester can be hydrolyzed with a mixture of aqueous sodium hydroxide and methanol.
- the methyl ether function can be removed by treatment of the free acid product of the previous procedure with 4-6 molar equivalents of a strong acid such as boron tribromide at 0°C in an inert solvent such as dichloromethane.
- a strong acid such as boron tribromide at 0°C in an inert solvent such as dichloromethane.
- Other combinations of protecting groups for the carboxylic acid present in 1 and phenolic hydroxyl in iodonium salt 2 can be employed, and their usage is known to those skilled in the art (references describing protecting group strategy include, for example, "Protecting Groups in Organic Chemistry", J. F. W. McOmie, Plenum Press, London, New York, 1973, and "Protective Groups in Organic Synthesis", T. W. Greene, Wiley, New York, 1984).
- the intermediate ester product 3 is reduced by treatment with an appropriate reducing agent such as diisobutyl aluminium hydride in an inert solvent such as tetrahydrofuran at 0°C. If R 2 and Ri are alkyl, then lithium aluminum hydride may be employed without the risk of reducing away halogen substituents at those positions. Standard work-up and purification yields the desired alcohol product 4.
- an appropriate reducing agent such as diisobutyl aluminium hydride in an inert solvent such as tetrahydrofuran at 0°C.
- R 2 and Ri are alkyl
- lithium aluminum hydride may be employed without the risk of reducing away halogen substituents at those positions.
- Standard work-up and purification yields the desired alcohol product 4.
- Other reducing agents may be employed and are known to those skilled in the art.
- Tetrazole derivative 8 can for instance be treated with an appropriate base such as sodium hydrogen carbonate in acetone, followed by N-alkylation with methyl iodide to afford derivatives 9 and 10, after standard work-up and purification procedures.
- an appropriate base such as sodium hydrogen carbonate in acetone
- N-alkylation with methyl iodide to afford derivatives 9 and 10
- Other alkylating agents and bases may be employed and are known to those skilled in the art.
- An amide library can also be prepared by solid phase synthesis (Examples 30-55).
- a methyl ester of intermediate 11 is loaded on a resin such as a Merrifield resin by standard procedures, well known to those skilled in the art.
- the resulting resin is then treated with sodium hydroxide in methanol to provide the resin-bond free carboxylic acid form of 11.
- Each resin pin is then filled with a solution of the corresponding aminoacid ester, PyBOP (benzotriazole-1-yl-oxy-tris-pyrrolidino phosphonium hexafluorophosphate). HBT.
- the amino acid product 12 can reduced by treatment with an appropriate reagent such as sodium borohydride in an polar solvent such as ethanol at room temperature. If R 2 and Ri are alkyl, then lithium aluminum hydride may be employed without the risk of reducing the halogen substituents at those positions. Standard work-up and purification yields the desired alcohol product. Other reducing agents may be employed and are known to those skilled in the art.
- Scheme 4 depicts a synthesis of compounds of formula I in which P is an acylsulphonamide. Similar procedures as for the coupling of amino acids above are employed.
- Dimethylformamide is added to the mixture if the sulphonamide does not dissolve completely.
- the desired acylsulphonamides (Example 58-70).
- Example 58-70, n 0
- Example 88-91, n l
- secondary diacetic acids amides are obtained through the treatment of 15 by dimethyhminodiacetate and EDCI in dimethylformamide or dichloromethane, followed by standard work-up procedures and final basic hydrolysis of the ester function (Example 206).
- a library comprising 100 diverse primary and secondary amides was also prepared in an automated fashion, using standard literature methods (Example 92-191).
- Ri, R , R 3 , R4 and n moieties are specifically defined, unless otherwise indicated, it is to be understood that Ri, R 2 , Ri, and R4 may be any of the groups encompassed thereby and n may be 0, 1, 2, 3 or 4.
- the compounds of the invention are agonist that are preferably selective for the thyroid hormone receptor-beta, and as such are useful in the treatment of obesity, hypercholesterolemia and atherosclerosis by lowering of serum LDL levels, alone or in combination with a lipid modulating drug such as an HMG-CoA reductase inhibitor, fibrate, thiazolidinedione, or MTP inhibitor, amelioration of depression alone or in combination with an antidepressant, and stimulation of bone formation to treat osteoporosis in combination with any known bone resorption inhibitor such as alendronate sodium.
- a lipid modulating drug such as an HMG-CoA reductase inhibitor, fibrate, thiazolidinedione, or MTP inhibitor
- the compounds of the invention may be useful as replacement therapy in elderly patients with hypothyroidism or subclinical hypothyroidism who are at risk of cardiovascular complications, in the treatment of the elderly to provide a sense of well-being, and in the treatment of non-toxic goiter; in the management of papillary or follicular thyroid cancer (alone or with T 4 ); in the treatment of skin disorders such as psoriasis, glaucoma, cardiovascular disease such as in the prevention or treatment of atherosclerosis, and congestive heart failure.
- the compounds of the invention may also be used to treat skin disorders or diseases involving dermal atrophy such as glucocorticoid induced dermal atrophy, including restoration of dermal atrophy induced by topical glucocorticoids.
- dermal atrophy induced by topical glucocorticoids such as the simultaneous treatment with topical glucocorticoid or a pharmacological product including both glucocorticoid and a compound of the invention
- the restoration/prevention of dermal atrophy induced by systemic treatment with glucocorticoids restoration/prevention of atrophy in the respiratory system induced by local treatment with glucocorticoids, UV-induced dermal atrophy, or dermal atrophy induced by aging (wrinkles, etc.)
- wound healing keloids, stria, cellulite, roughened skin, actinic skin damage, lichen planus, ichtyosis. acne, psoriasis.
- the compounds of the invention may be used in combination with a retinoid or a vitamin D analog.
- the compounds of the invention can be administered orally or parenterally such as subcutaneously or intravenously, as well as by nasal application, rectally or sublingually to various mammalian species known to be subject to such maladies, e.g., humans, cats, dogs and the like in an effective amount within the dosage range of about 0.1 to about 100 mg/kg, preferably about 0.2 to about 50 mg/kg and more preferably about 0.5 to about 25 mg/kg (or from about 1 to about 2500 mg, preferably from about 5 to about 2000 mg) on a regimen in single or 2 to 4 divided daily doses.
- the active substance can be utilized in a composition such as tablet, capsule, ointment, hydrophilic ointment, cream, lotion, solution or suspension or in other types of carrier of materials such as transdermal devices, iontophoretic devices, rectal suppositories, inhalant devices and the like.
- the composition or carrier will contain about 5 to about 500 mg per unit of dosage of a compound of formula I. They may be compounded in conventional matter with a physiologically acceptable vehicle or carrier, excipient, binder, preservative, stabilizer, flavor, etc., as called for by accepted pharmaceutical practice.
- Example 28 D-N- [3 , 5 -Dibromo-4-(4-hydroxy-3 -isopropylphenoxy)phenylacetyl] aspargine.
- 3,5-Dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetic acid (444 mg) was mixed with 10 ml thionyl chloride and heated at reflux for 3 h. The reaction mixture was co-evaporated with toluene to give the crude 3,5-dibromo-4-(4-hydroxy-3-isopropyl- phenoxy)phenylacetyl chloride. N,O-bis(trimethylsilyl)acetamide (670 mg) was added at 0 ° C, under nitrogen atmosphere, to a mixture of D- Aspargine (225 mg) and 10 ml acetonitrile.
- the resin (100 mg) was treated with a mixture of trifluoroacetic acid, dimethyl sulphite and water (85:15:5). The mixture was stirred at room temperature for two days. The resin was removed by filtration and the organic phase was collected and concentrated under vacuum. The resulting residue was chromatographed on silica gel (methanol/chloroform/ acetic acid 10:90: 1). The pure fractions were pooled and concentrated affording 17.5 mg (51%>) of 3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)benzoic acid as white solid. The loading rate was estimated as 0.04 mmol (17,5 mg) per 100 mg of loaded resin.
- DIVERSOMER ® 8-100 synthesizer was used for syntheses and Savant SpeedVac ® system for concentration.
- a 50 ml stock solution of trifluoroacetic acid/dimethyl sulphite/water(85:15:5; v/v) was prepared.
- the solution (5 ml) was added to each of the eight PINs in 1 ml increments.
- the apparatus was allowed to stand in a fume hood with stirring for 2 days.
- the resercoir rack and the holder block was disassembled.
- Each PIN was washed with 1 ml of the above solution.
- the contents of the 8 reservoir vials were concentrated to dryness.
- Each vial was partitioned between aqueous hydrochloric acid (1 ml, 1 M) and ethyl acetate (2 ml).
- Example 61 3,5-Dibromo-4-(4-hydroxy-3-isopropylphenoxy)benzoyl sulfamide 3,5-Dibromo-4-(4-methoxy-3-isopropylphenoxy)benzoic acid (0.035 mmol) was coupled with sulfamide (0.175 mmol) using the method described in Example 58. Purification on HPLC of the residue gave 13 mg (73 %) of the title compound.
- Example 71 I-Dimethyl-N-[3,5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetyl]glutamate 3,5-Dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetic acid (200 mg) was coupled with Z-dimethyl glutamate hydrochloride (190 mg) using the method described in Example 25(a). The crude mixture was purified by semi-preparative HPLC, to give 150 mg (55%) of the title compound. LC-MS (electrospray): m/z 601 (M+H).
- Example 78 N-[3,5-Dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetyl]glutamine 3,5-Dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetic acid (200 mg) was coupled with I-tert-butyl glutamine hydrochloride (230 mg) using the method described in Example 25(a) and subsequently hydrolyzed using the method described in Example 25(b). The crude mixture was purified by semi-preparative HPLC, to give 40 mg (15%) of the title 5 compound.
- LC-MS elctrospray
- I-Methyl-N-[3.5-dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetyl]- homoserine (100 mg) was hydrolyzed using the method described in Example 25(b). The crude product was purified by HPLC to give 30 mg (30%) of I-N-[3,5-dibromo-4-(4- hydroxy-3-isopropyl-phenoxy)phenylacetyl]homoserine
- N-methylmorpholine (5.7 g, 6.2 mL, 56.35 mmol) was added under N 2 and the reaction mixture was allowed to attain room temperature. After 18 h, CH 2 C1 2 was removed in vacuo and the residue partionated beetween EtOAc (300 mL) and H 2 O (150 mL). The organic phase was successively washed with IN HC1 (2 x 150 mL), saturated aqueous NaHCO 3 (2 x 150 mL), and brine ( 2 x 150 mL). The organic phase was dried (Na 2 SO 4 ), filtered and concentrated in vacuo to give 11.5 g of crude product as an orange solid.
- Example 88 3 5-Dibromo-4-(4-hydroxy-3-isopropylphenoxy)phenylacetyl-5-dimethylamino- 1 -naphthalen esulphonamide
- dimethylaminopyridine 4 mg, 0.018 mmol
- 5-dimethylamino- 1-naphthalenesulphonamide 45 mg, 0.18 mmol
- dichloromethane in dimethyl formamide 0.2 ml
- l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride 28 mg, 0.13 mmol
- diisopropylethyl amine 17 mg, 0.13 mmol
- reaction mixture was vortexed and allowed to stand at room temperature for 6 hours. A solution of ammonium fluoride (0.5 M in methanol; 0.4 ml) was added. After 16 hours, the reaction mixture was evaporated to dryness, re-dissolved in a solvent mixture containing 90% methanol, 10% water and 0.1% trifluoroacetic acid (2 ml) and purified by preparative HPLC (YMC S5 ODS 30 x 250 mm: 50-100%) solvent B in 30 min: solvent A - 90% water, 10% methanol, 0.1% trifluoroacetic acid; solvent B - 10% water, 90% methanol, 0.1% trifluoroacetic acid: flow rate 25 ml per min: detection 220 nm). The yield was 10.1 mg (16%).
- Example 89-91 These compounds were prepared and purified in a similar manner as above.
- Examples 88-91 comprising the coupled sulphonamide, retention times and mass spectra, see Scheme below.
- the ester was prepared by adding the reagents to the reaction in the manner described in Example 207.
- the starting acid 122 mg, 0.356 mmol
- B-alanine methyl ester hydrochloride. and hydroxybenzotriazole (240 mg, 1.76 mmol) were dissolved in triethyl amine (0.6 mL. 2.5 mmol), dichloromethane 1.2 mL, and 0.8 mL of dimethylamide.
- Thel- (3-dimethylaminopropyl)-3-ethylcarbodiimide hydrogen chloride 110 mg, 0.58 mmol
- the ester 75 mg, 50 %) was isolated without further purification.
- Example 210 D-N-[3,5-Dichloro-4-(4-hydroxy-3-isopropylphenoxy)benzoyl]serine 3,5-Dichloro-4-(4-hydroxy-3-isopropylphenoxy)benzoic acid (122 mg) was coupled with D-serin methyl ester hydrochloride using the method described in Example 207(a) and subsequently hydrolyzed using the method described in Example 207(b). The crude mixture was purified as above. Satisfactory 'H-NMR, 13 C-NMR and mass spectra was obtained for the title compound.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Dermatology (AREA)
- Diabetes (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Ophthalmology & Optometry (AREA)
- Neurology (AREA)
- Psychiatry (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Hydrogenated Pyridines (AREA)
- Pyridine Compounds (AREA)
Abstract
Description
Claims
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR9916851-0A BR9916851A (en) | 1998-12-24 | 1999-12-23 | Thyroid receptor ligands and method ii |
IL14379999A IL143799A0 (en) | 1998-12-24 | 1999-12-23 | Phenoxyphenyl derivatives and pharmaceutical compositions containing the same |
KR1020017007766A KR20010108032A (en) | 1998-12-24 | 1999-12-23 | Thyroid receptor ligands |
EP99962486A EP1144370A2 (en) | 1998-12-24 | 1999-12-23 | Thyroid receptor ligands |
JP2000590990A JP4405088B2 (en) | 1998-12-24 | 1999-12-23 | Novel thyroid receptor ligands and method II |
NZ512422A NZ512422A (en) | 1998-12-24 | 1999-12-23 | Novel thyroid receptor ligands and method II |
US09/868,889 US6989402B1 (en) | 1998-12-24 | 1999-12-23 | Thyroid receptor ligands and method II |
CA002356319A CA2356319A1 (en) | 1998-12-24 | 1999-12-23 | Thyroid receptor ligands |
HU0104666A HUP0104666A3 (en) | 1998-12-24 | 1999-12-23 | Thyroid receptor ligands |
AU18855/00A AU758202B2 (en) | 1998-12-24 | 1999-12-23 | Novel thyroid receptor ligands and method II |
NO20012931A NO20012931L (en) | 1998-12-24 | 2001-06-13 | New thyroid receptor ligands and method II |
US11/189,654 US7288571B2 (en) | 1998-12-24 | 2005-07-26 | Thyroid receptor ligands and method II |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9828442.5 | 1998-12-24 | ||
GBGB9828442.5A GB9828442D0 (en) | 1998-12-24 | 1998-12-24 | Novel thyroid receptor ligands and method II |
Related Child Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09868889 A-371-Of-International | 1999-12-23 | ||
US11/189,654 Division US7288571B2 (en) | 1998-12-24 | 2005-07-26 | Thyroid receptor ligands and method II |
Publications (2)
Publication Number | Publication Date |
---|---|
WO2000039077A2 true WO2000039077A2 (en) | 2000-07-06 |
WO2000039077A3 WO2000039077A3 (en) | 2000-09-21 |
Family
ID=10844889
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB1999/002084 WO2000039077A2 (en) | 1998-12-24 | 1999-12-23 | Thyroid receptor ligands |
Country Status (19)
Country | Link |
---|---|
US (2) | US6989402B1 (en) |
EP (1) | EP1144370A2 (en) |
JP (1) | JP4405088B2 (en) |
KR (1) | KR20010108032A (en) |
CN (1) | CN1186332C (en) |
AU (1) | AU758202B2 (en) |
BR (1) | BR9916851A (en) |
CA (1) | CA2356319A1 (en) |
CZ (1) | CZ20012204A3 (en) |
GB (1) | GB9828442D0 (en) |
HU (1) | HUP0104666A3 (en) |
ID (1) | ID29013A (en) |
IL (1) | IL143799A0 (en) |
NO (1) | NO20012931L (en) |
NZ (1) | NZ512422A (en) |
RU (1) | RU2001120701A (en) |
TR (1) | TR200101834T2 (en) |
WO (1) | WO2000039077A2 (en) |
ZA (1) | ZA200104932B (en) |
Cited By (110)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1127882A1 (en) * | 2000-01-25 | 2001-08-29 | Pfizer Products Inc. | Tetrazole compounds as thyroid receptor ligands |
WO2001076589A1 (en) * | 2000-04-06 | 2001-10-18 | Ipsat Therapies Oy | Dermatological use and a dermatological preparation |
WO2001094293A2 (en) * | 2000-06-07 | 2001-12-13 | Bristol-Myers Squibb Company | Benzamide ligands for the thyroid receptor |
WO2002012169A1 (en) * | 2000-08-04 | 2002-02-14 | Bayer Aktiengesellschaft | Amino diphenyl ethers and amido diphenyl ethers |
WO2002044120A1 (en) * | 2000-11-29 | 2002-06-06 | Karo Bio Ab | Compounds active at the glucocorticoid receptor iii |
WO2002051805A1 (en) * | 2000-12-27 | 2002-07-04 | Bayer Aktiengesellschaft | Indole derivatives as ligands of thyroid receptors |
WO2002062780A2 (en) * | 2001-02-08 | 2002-08-15 | Karo Bio Ab | Phenoxy substituted benzocondensed heteroaryl derivatives as thyroid receptor ligands |
WO2002090344A1 (en) * | 2001-05-09 | 2002-11-14 | Bayer Aktiengesellschaft | Amido-diphenyl derivatives |
WO2003018515A2 (en) * | 2001-08-24 | 2003-03-06 | Karo Bio Ab | Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders |
WO2003064369A1 (en) * | 2002-01-30 | 2003-08-07 | Kissei Pharmaceutical Co., Ltd. | Novel thyroid hormone receptor ligand, medicinal compositions containing the same and use thereof |
WO2003084915A1 (en) * | 2002-04-11 | 2003-10-16 | Karo Bio Ab | Novel thyroid receptor ligands |
US6664291B2 (en) | 2000-03-31 | 2003-12-16 | Pfizer, Inc. | Malonamic acids and derivatives thereof as thyroid receptor ligands |
WO2004007430A2 (en) * | 2002-07-10 | 2004-01-22 | Karo Bio Ab | Benzamide or phenylacetamide derivatives useful as thyroid receptor ligands |
US6723744B2 (en) | 2001-09-26 | 2004-04-20 | Pfizer, Inc. | Indole carboxylic acids as thyroid receptor ligands |
US6777442B2 (en) | 2001-03-12 | 2004-08-17 | Bayer Aktiengesellschaft | Diphenyl derivatives |
EP1477475A1 (en) * | 2003-05-16 | 2004-11-17 | Procorde GmbH | Compounds for use as a medicine increasing the contractility of a heart, a heart muscle or cells of a heart muscle |
WO2005009433A1 (en) * | 2003-07-24 | 2005-02-03 | Fernando Goglia | Use of 3,5 diiodothyronine as regulators of lipid metabolism |
WO2005120477A3 (en) * | 2004-06-07 | 2006-03-02 | Merck & Co Inc | N- (2-benzyl) -2-phenylbutanamides as androgen receptor modulators |
JP2006511474A (en) * | 2002-09-19 | 2006-04-06 | イーライ・リリー・アンド・カンパニー | Diaryl ethers as opioid receptor antagonists |
WO2006076509A1 (en) | 2005-01-13 | 2006-07-20 | Bristol-Myers Squibb Company | Heterocyclic modulators of the glucocorticoid receptor, ap-1, and/or nf-kb activity and use thereof |
WO2006138682A1 (en) | 2005-06-17 | 2006-12-28 | Bristol-Myers Squibb Company | Azabicyclic heterocycles as cannabinoid receptor modulators |
WO2007018314A2 (en) * | 2005-08-10 | 2007-02-15 | Takeda Pharmaceutical Company Limited | Therapeutic agent for diabetes |
WO2007053819A2 (en) | 2005-10-31 | 2007-05-10 | Bristol-Myers Squibb Company | Pyrrolidinyl beta-amino amide-based inhibitors of dipeptidyl peptidase iv and methods |
CN1332921C (en) * | 2001-08-24 | 2007-08-22 | 卡罗生物股份公司 | Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders |
WO2007120083A1 (en) * | 2006-04-13 | 2007-10-25 | Astrazeneca Ab | The use of carboxamide derivatives in the manufacture of a medicament for the treatment of inflammatory, allergic and dermatological conditions |
WO2007120729A2 (en) * | 2006-04-12 | 2007-10-25 | Merck & Co., Inc. | Pyridyl amide t-type calcium channel antagonists |
WO2007132475A1 (en) * | 2006-05-15 | 2007-11-22 | Cadila Healthcare Limited | Selective tr-beta 1 agonist |
WO2007139589A1 (en) | 2006-05-26 | 2007-12-06 | Bristol-Myers Squibb Company | Sustained release glp-1 receptor modulators |
US7317012B2 (en) | 2005-06-17 | 2008-01-08 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoind-1 receptor modulators |
EP1908466A1 (en) * | 2005-07-19 | 2008-04-09 | Daiichi Sankyo Company, Limited | Substituted propanamide derivative and pharmaceutical composition containing the same |
WO2008057857A1 (en) | 2006-11-01 | 2008-05-15 | Bristol-Myers Squibb Company | MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-ϰB ACTIVITY AND USE THEREOF |
WO2008057862A2 (en) | 2006-11-01 | 2008-05-15 | Bristol-Myers Squibb Company | MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-ϰB ACTIVITY AND USE THEREOF |
WO2008092771A1 (en) * | 2007-01-31 | 2008-08-07 | Ciba Holding Inc. | Cationic dyes |
US7452892B2 (en) | 2005-06-17 | 2008-11-18 | Bristol-Myers Squibb Company | Triazolopyrimidine cannabinoid receptor 1 antagonists |
US7504413B2 (en) | 2004-05-06 | 2009-03-17 | Cytokinetics, Inc. | N-(4-(imidazo[1,2A]pyridin-YL)phenethyl)benzamide inhibitors of the mitotic kinesin CENP-E for treating certain cellular proliferation diseases |
US7504435B2 (en) | 2001-01-31 | 2009-03-17 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Method for stimulating weight loss and/or for lowering triglycerides in patients |
US7521557B2 (en) | 2005-05-20 | 2009-04-21 | Bristol-Myers Squibb Company | Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods |
WO2009058944A2 (en) | 2007-11-01 | 2009-05-07 | Bristol-Myers Squibb Company | Nonsteroidal compounds useful as modulators of glucocorticoid receptor ap-1 and /or nf- kappa b activity and use thereof |
US7553836B2 (en) | 2006-02-06 | 2009-06-30 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
WO2009080835A1 (en) * | 2007-12-24 | 2009-07-02 | Karo Bio Ab | Thyromimetric compounds in treatment of disease related to sonic hedgehog signalling |
US7572808B2 (en) | 2005-06-17 | 2009-08-11 | Bristol-Myers Squibb Company | Triazolopyridine cannabinoid receptor 1 antagonists |
US7618981B2 (en) | 2004-05-06 | 2009-11-17 | Cytokinetics, Inc. | Imidazopyridinyl-benzamide anti-cancer agents |
US7632837B2 (en) | 2005-06-17 | 2009-12-15 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid-1 receptor modulators |
WO2010049946A2 (en) | 2008-10-27 | 2010-05-06 | Cadila Healthcare Limited | Thyroid receptor ligands |
WO2010086878A2 (en) | 2009-01-09 | 2010-08-05 | Cadila Healthcare Limited | Thyroid receptor modulators |
US7795448B2 (en) | 2004-05-06 | 2010-09-14 | Cytokinetics, Incorporated | Imidazoyl-benzamide anti-cancer agents |
US7795436B2 (en) | 2005-08-24 | 2010-09-14 | Bristol-Myers Squibb Company | Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists |
WO2010111665A1 (en) | 2009-03-27 | 2010-09-30 | Bristol-Myers Squibb Company | Methods for preventing major adverse cardiovascular events with dpp-iv inhibitors |
US7812048B2 (en) | 2007-07-27 | 2010-10-12 | Bristol-Myers Squibb Company | Glucokinase activators and methods of using same |
WO2010122980A1 (en) | 2009-04-20 | 2010-10-28 | 田辺三菱製薬株式会社 | Novel thyroid hormone β receptor agonist |
US7829552B2 (en) | 2003-11-19 | 2010-11-09 | Metabasis Therapeutics, Inc. | Phosphorus-containing thyromimetics |
EP2298776A1 (en) | 2005-10-26 | 2011-03-23 | Bristol-Myers Squibb Company | Thienopyrimidinone derivatives as melanin concentrating hormone receptor-1 antagonists |
US7943656B2 (en) | 2007-04-20 | 2011-05-17 | Bristol-Myers Squibb Company | Crystal forms of saxagliptin and processes for preparing same |
WO2011060256A2 (en) | 2009-11-13 | 2011-05-19 | Bristol-Myers Squibb Company | Bilayer tablet formulations |
WO2011060255A1 (en) | 2009-11-13 | 2011-05-19 | Bristol-Myers Squibb Company | Reduced mass metformin formulations |
WO2011060290A2 (en) | 2009-11-13 | 2011-05-19 | Bristol-Myer Squibb Company | Immediate release tablet formulations |
US7989433B2 (en) | 2008-05-29 | 2011-08-02 | Bristol-Myers Squibb Company | Substituted thieno[3,2-D]pyrimidines as melanin concentrating hormone receptor-1 antagonists |
WO2011103126A1 (en) * | 2010-02-17 | 2011-08-25 | Ampla Pharmaceuticals Inc. | Treatment of metabolic syndrome with piperidine amides |
US8012984B2 (en) | 2007-07-06 | 2011-09-06 | Bristol-Myers Squibb Company | Substituted pyrazinone melanin concentrating hormone receptor-1 antagonists and methods |
WO2011130459A1 (en) | 2010-04-14 | 2011-10-20 | Bristol-Myers Squibb Company | Novel glucokinase activators and methods of using same |
EP2457918A2 (en) | 2006-06-28 | 2012-05-30 | Bristol-Myers Squibb Company | Crystalline solvates and complexes of (1s)-1,5-anhydro-1-c-(3-((phenyl) methyl) phenyl)-d-glucitol derivatives with amino acids as SGLT2 inhibitors for the treatment of diabetes |
EP2474549A1 (en) | 2007-04-17 | 2012-07-11 | Bristol-Myers Squibb Company | Fused heterocyclic 11-beta-hydroxysteroid dehydrogenase type I inhibitors |
EP2527317A1 (en) | 2006-08-24 | 2012-11-28 | Bristol-Myers Squibb Company | Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors |
EP2527337A1 (en) | 2005-04-14 | 2012-11-28 | Bristol-Myers Squibb Company | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
US8399518B2 (en) | 2007-02-27 | 2013-03-19 | University Of Arizona Office Of Technology Transfer | Administration of 3,5-diiodothyropropionic acid for stimulating weight loss, and/or lowering triglyceride levels, and/or treatment of metabolic syndrome |
US8592629B2 (en) | 2010-07-12 | 2013-11-26 | Pfizer Limited | Sulfonamide derivatives as Nav 1.7 inhibitors |
WO2014039412A1 (en) | 2012-09-05 | 2014-03-13 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
US8685977B2 (en) | 2010-07-12 | 2014-04-01 | Pfizer Limited | Chemical compounds |
WO2014008458A3 (en) * | 2012-07-06 | 2014-04-17 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
US8772343B2 (en) | 2010-07-12 | 2014-07-08 | Pfizer Limited | Chemical compounds |
US8772293B2 (en) | 2010-07-09 | 2014-07-08 | Pfizer Limited | Chemical compounds |
US8835498B2 (en) | 2008-11-19 | 2014-09-16 | Pola Chemical Industries Inc. | Anti-wrinkle agents |
WO2015027021A1 (en) | 2013-08-22 | 2015-02-26 | Bristol-Myers Squibb Company | Imide and acylurea derivatives as modulators of the glucocorticoid receptor |
US9085517B2 (en) | 2011-12-15 | 2015-07-21 | Pfizer Limited | Sulfonamide derivatives |
US9096500B2 (en) | 2010-07-12 | 2015-08-04 | Pfizer Limited | Acyl sulfonamide compounds |
US9102621B2 (en) | 2010-07-12 | 2015-08-11 | Pfizer Limited | Acyl sulfonamide compounds |
US9481677B2 (en) | 2011-10-31 | 2016-11-01 | Xenon Pharmaceuticals Inc. | Biaryl ether sulfonamides and their use as therapeutic agents |
US9493429B2 (en) | 2013-03-15 | 2016-11-15 | Genentech, Inc. | Substituted benzoxazoles and methods of use thereof |
US9546164B2 (en) | 2013-11-27 | 2017-01-17 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
US9550775B2 (en) | 2013-03-14 | 2017-01-24 | Genentech, Inc. | Substituted triazolopyridines and methods of use thereof |
US9586900B2 (en) | 2012-09-05 | 2017-03-07 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
US9630929B2 (en) | 2011-10-31 | 2017-04-25 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
US9771376B2 (en) | 2000-05-22 | 2017-09-26 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
US10005724B2 (en) | 2014-07-07 | 2018-06-26 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US10130643B2 (en) | 2005-05-26 | 2018-11-20 | Metabasis Therapeutics, Inc. | Thyromimetics for the treatment of fatty liver diseases |
US10179767B2 (en) | 2015-05-22 | 2019-01-15 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
WO2019054514A1 (en) | 2017-09-14 | 2019-03-21 | 国立研究開発法人理化学研究所 | Method for producing retinal tissues |
WO2019079119A1 (en) * | 2017-10-17 | 2019-04-25 | IFM Tre, Inc. | Sulphonamides and compositions thereof for treating conditions associated with nlrp activity |
US10457654B2 (en) | 2016-10-17 | 2019-10-29 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
EP3497077A4 (en) * | 2016-08-12 | 2020-01-22 | Oregon Health & Science University | Amide compounds, pharmaceutical compositions thereof, and methods of using the same |
WO2020016335A1 (en) | 2018-07-19 | 2020-01-23 | Astrazeneca Ab | Methods of treating hfpef employing dapagliflozin and compositions comprising the same |
US10766858B2 (en) | 2016-03-30 | 2020-09-08 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
WO2020184720A1 (en) | 2019-03-13 | 2020-09-17 | 大日本住友製薬株式会社 | Method for evaluating quality of transplant neural retina, and transplant neural retina sheet |
US10787446B2 (en) | 2015-09-28 | 2020-09-29 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US10899732B2 (en) | 2015-11-25 | 2021-01-26 | Genentech, Inc. | Substituted benzamides useful as sodium channel blockers |
US10947251B2 (en) | 2018-03-30 | 2021-03-16 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US11028075B2 (en) | 2018-02-26 | 2021-06-08 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US11130726B2 (en) | 2015-08-27 | 2021-09-28 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US11202789B2 (en) | 2016-11-21 | 2021-12-21 | Viking Therapeutics, Inc. | Method of treating glycogen storage disease |
WO2022054925A1 (en) | 2020-09-11 | 2022-03-17 | 国立研究開発法人理化学研究所 | Complex containing neural retina-containing cell aggregates and matrix, and method for manufacturing same |
WO2022054924A1 (en) | 2020-09-11 | 2022-03-17 | 大日本住友製薬株式会社 | Medium for tissue for transplantation |
US11447460B2 (en) | 2016-04-18 | 2022-09-20 | Novartis Ag | Compounds and compositions for treating conditions associated with NLRP activity |
WO2023090427A1 (en) | 2021-11-19 | 2023-05-25 | 国立研究開発法人理化学研究所 | Production method for sheet-like retinal tissue |
US11667606B2 (en) | 2019-03-01 | 2023-06-06 | Autobahn Therapeutics, Inc. | Thyromimetics |
US11707472B2 (en) | 2017-06-05 | 2023-07-25 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis |
US11752173B2 (en) | 2017-12-19 | 2023-09-12 | Beijing Jiyuan Biological Technology Co., Ltd. | FGF21 and GLP1 double gene-modified mesenchymal stem cell and use in treating a metabolic disease |
EP4245299A2 (en) | 2007-03-22 | 2023-09-20 | Astrazeneca AB | Pharmaceutical formulations containing dapagliflozin propylene glycol hydrate |
US11787828B2 (en) | 2018-03-22 | 2023-10-17 | Viking Therapeutics, Inc. | Crystalline forms and methods of producing crystalline forms of a compound |
US11827596B2 (en) | 2018-12-12 | 2023-11-28 | Autobahn Therapeutics, Inc. | Thyromimetics |
US12102646B2 (en) | 2018-12-05 | 2024-10-01 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis and inflammation |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7163918B2 (en) * | 2000-08-22 | 2007-01-16 | New River Pharmaceuticals Inc. | Iodothyronine compositions |
KR20070054762A (en) | 2003-11-12 | 2007-05-29 | 페노믹스 코포레이션 | Heterocyclic boronic acid compounds |
US7576121B2 (en) * | 2003-11-12 | 2009-08-18 | Phenomix Corporation | Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
US7767828B2 (en) * | 2003-11-12 | 2010-08-03 | Phenomix Corporation | Methyl and ethyl substituted pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
US7317109B2 (en) * | 2003-11-12 | 2008-01-08 | Phenomix Corporation | Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
US7825139B2 (en) * | 2005-05-25 | 2010-11-02 | Forest Laboratories Holdings Limited (BM) | Compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
TW200738621A (en) * | 2005-11-28 | 2007-10-16 | Astrazeneca Ab | Chemical process |
WO2009038974A1 (en) * | 2007-09-20 | 2009-03-26 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
AU2008317353B2 (en) * | 2007-10-24 | 2014-08-07 | Merck Sharp & Dohme Llc | Heterocycle phenyl amide T-type calcium channel antagonists |
AR081331A1 (en) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | AMINO- PYRIMIDINES COMPOSITIONS OF THE SAME AND METHODS FOR THE USE OF THE SAME |
WO2011133920A1 (en) | 2010-04-23 | 2011-10-27 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
AR081626A1 (en) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | AMINO-PYRIDAZINIC COMPOUNDS, PHARMACEUTICAL COMPOSITIONS THAT CONTAIN THEM AND USE OF THE SAME TO TREAT CARDIAC AND SKELETIC MUSCULAR DISORDERS |
US20150291514A1 (en) * | 2012-01-04 | 2015-10-15 | Pfizer Limted | N-Aminosulfonyl Benzamides |
CN102718718B (en) * | 2012-05-31 | 2014-09-24 | 绍兴文理学院 | Preparation method for 3,5-dibromo-4-(5-benzimidazole oxygen group)phenylacetic acid |
CN103709094B (en) * | 2014-01-07 | 2016-04-06 | 厦门大学 | 4-phenoxy benzamide compounds and its preparation method and application |
CN106588690B (en) * | 2016-12-19 | 2019-06-04 | 广西中医药大学 | The preparation method of Holotrichia trichophora A prime Abrusamide |
JP2020511511A (en) | 2017-03-24 | 2020-04-16 | ジェネンテック, インコーポレイテッド | 4-Piperidin-N- (pyrimidin-4-yl) chroman-7-sulfonamide derivatives as sodium channel inhibitors |
WO2021026179A1 (en) * | 2019-08-06 | 2021-02-11 | Bristol-Myers Squibb Company | AGONISTS OF ROR GAMMAt |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3231541A1 (en) * | 1982-08-25 | 1984-03-01 | Henning Berlin Gmbh Chemie- Und Pharmawerk, 1000 Berlin | Pharmaceutical composition containing 3,3',5-triiodothyronamine and process for its preparation |
US4741897A (en) * | 1986-07-08 | 1988-05-03 | Baxter Travenol | Thyroxine analogs and reagents for thyroid hormone assays |
EP0580550A1 (en) * | 1992-07-21 | 1994-01-26 | Ciba-Geigy Ag | Oxamic acid derivatives as hypocholesteremic agents |
WO1996040048A2 (en) * | 1995-06-07 | 1996-12-19 | Karo Bio Ab | Novel uses for thyroid hormones or thyroid hormone-like compounds |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6335459B1 (en) | 1998-12-23 | 2002-01-01 | Syntex (U.S.A.) Llc | Aryl carboxylic acid and aryl tetrazole derivatives as IP receptor modulators |
US6395784B1 (en) * | 2000-06-07 | 2002-05-28 | Bristol-Myers Squibb Company | Benzamide ligands for the thyroid receptor |
-
1998
- 1998-12-24 GB GBGB9828442.5A patent/GB9828442D0/en not_active Ceased
-
1999
- 1999-12-23 KR KR1020017007766A patent/KR20010108032A/en not_active Application Discontinuation
- 1999-12-23 BR BR9916851-0A patent/BR9916851A/en not_active IP Right Cessation
- 1999-12-23 ID IDW00200101489A patent/ID29013A/en unknown
- 1999-12-23 CA CA002356319A patent/CA2356319A1/en not_active Abandoned
- 1999-12-23 US US09/868,889 patent/US6989402B1/en not_active Expired - Fee Related
- 1999-12-23 CN CNB998150576A patent/CN1186332C/en not_active Expired - Fee Related
- 1999-12-23 RU RU2001120701/04A patent/RU2001120701A/en not_active Application Discontinuation
- 1999-12-23 JP JP2000590990A patent/JP4405088B2/en not_active Expired - Fee Related
- 1999-12-23 EP EP99962486A patent/EP1144370A2/en not_active Withdrawn
- 1999-12-23 AU AU18855/00A patent/AU758202B2/en not_active Ceased
- 1999-12-23 WO PCT/IB1999/002084 patent/WO2000039077A2/en not_active Application Discontinuation
- 1999-12-23 NZ NZ512422A patent/NZ512422A/en unknown
- 1999-12-23 TR TR2001/01834T patent/TR200101834T2/en unknown
- 1999-12-23 IL IL14379999A patent/IL143799A0/en unknown
- 1999-12-23 CZ CZ20012204A patent/CZ20012204A3/en unknown
- 1999-12-23 HU HU0104666A patent/HUP0104666A3/en unknown
-
2001
- 2001-06-13 NO NO20012931A patent/NO20012931L/en not_active Application Discontinuation
- 2001-06-15 ZA ZA200104932A patent/ZA200104932B/en unknown
-
2005
- 2005-07-26 US US11/189,654 patent/US7288571B2/en not_active Expired - Fee Related
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE3231541A1 (en) * | 1982-08-25 | 1984-03-01 | Henning Berlin Gmbh Chemie- Und Pharmawerk, 1000 Berlin | Pharmaceutical composition containing 3,3',5-triiodothyronamine and process for its preparation |
US4741897A (en) * | 1986-07-08 | 1988-05-03 | Baxter Travenol | Thyroxine analogs and reagents for thyroid hormone assays |
EP0580550A1 (en) * | 1992-07-21 | 1994-01-26 | Ciba-Geigy Ag | Oxamic acid derivatives as hypocholesteremic agents |
WO1996040048A2 (en) * | 1995-06-07 | 1996-12-19 | Karo Bio Ab | Novel uses for thyroid hormones or thyroid hormone-like compounds |
Non-Patent Citations (4)
Title |
---|
DATABASE CHEMABS [Online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US STN, CAPLUS accession no. 1971:540431, XP002139408 -& CHEMICAL ABSTRACTS, vol. 75, no. 23, 6 December 1971 (1971-12-06) Columbus, Ohio, US; abstract no. 140431, XP002139407 & K. MASUDA ET AL: TAKEDA KENKYUSHO HO, vol. 29, no. 4, 1970, pages 545-552, * |
M. ADAMCZYK ET AL: BIOCONJUGATE CHEM., vol. 8, no. 2, 1997, pages 133-145, XP000906993 * |
M. ANDRE ET AL: J. CHROMATOGR. A, vol. 725, no. 2, 1996, pages 287-294, XP004039616 * |
M. EBISAWA ET AL: CHEM. PHARM. BULL., vol. 47, no. 9, 1999, pages 1348-1350, XP000906992 * |
Cited By (173)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6441015B2 (en) | 2000-01-25 | 2002-08-27 | Pfizer Inc. | Tetrazole compounds as thyroid receptor ligands |
EP1127882A1 (en) * | 2000-01-25 | 2001-08-29 | Pfizer Products Inc. | Tetrazole compounds as thyroid receptor ligands |
US6924310B2 (en) | 2000-03-31 | 2005-08-02 | Pfizer Inc. | Malonamic acids and derivatives thereof as thyroid receptor ligands |
US6664291B2 (en) | 2000-03-31 | 2003-12-16 | Pfizer, Inc. | Malonamic acids and derivatives thereof as thyroid receptor ligands |
US7202275B2 (en) | 2000-03-31 | 2007-04-10 | Warner Lambert Company Llc | Malonamic acids and derivatives thereof as thyroid receptor ligands |
WO2001076589A1 (en) * | 2000-04-06 | 2001-10-18 | Ipsat Therapies Oy | Dermatological use and a dermatological preparation |
GB2377380B (en) * | 2000-04-06 | 2004-07-14 | Ipsat Therapies Oy | Dermatological use and a dermatological preparation |
GB2377380A (en) * | 2000-04-06 | 2003-01-15 | Ipsat Therapies Oy | Dermatological use and a dermatological preparation |
US9771376B2 (en) | 2000-05-22 | 2017-09-26 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
WO2001094293A2 (en) * | 2000-06-07 | 2001-12-13 | Bristol-Myers Squibb Company | Benzamide ligands for the thyroid receptor |
WO2001094293A3 (en) * | 2000-06-07 | 2002-06-06 | Bristol Myers Squibb Co | Benzamide ligands for the thyroid receptor |
WO2002012169A1 (en) * | 2000-08-04 | 2002-02-14 | Bayer Aktiengesellschaft | Amino diphenyl ethers and amido diphenyl ethers |
WO2002044120A1 (en) * | 2000-11-29 | 2002-06-06 | Karo Bio Ab | Compounds active at the glucocorticoid receptor iii |
WO2002051805A1 (en) * | 2000-12-27 | 2002-07-04 | Bayer Aktiengesellschaft | Indole derivatives as ligands of thyroid receptors |
US6794406B2 (en) | 2000-12-27 | 2004-09-21 | Bayer Aktiengesellschaft | Indole derivatives |
US7504435B2 (en) | 2001-01-31 | 2009-03-17 | The Arizona Board Of Regents On Behalf Of The University Of Arizona | Method for stimulating weight loss and/or for lowering triglycerides in patients |
WO2002062780A3 (en) * | 2001-02-08 | 2002-09-26 | Karobio Ab | Phenoxy substituted benzocondensed heteroaryl derivatives as thyroid receptor ligands |
WO2002062780A2 (en) * | 2001-02-08 | 2002-08-15 | Karo Bio Ab | Phenoxy substituted benzocondensed heteroaryl derivatives as thyroid receptor ligands |
US7144909B2 (en) | 2001-02-08 | 2006-12-05 | Karo Bio Ab | Phenoxy substituted benzocondensed heteroaryl derivatives as thyroid receptor ligands |
US6777442B2 (en) | 2001-03-12 | 2004-08-17 | Bayer Aktiengesellschaft | Diphenyl derivatives |
WO2002090344A1 (en) * | 2001-05-09 | 2002-11-14 | Bayer Aktiengesellschaft | Amido-diphenyl derivatives |
WO2003018515A2 (en) * | 2001-08-24 | 2003-03-06 | Karo Bio Ab | Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders |
WO2003018515A3 (en) * | 2001-08-24 | 2004-10-28 | Karobio Ab | Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders |
CN1332921C (en) * | 2001-08-24 | 2007-08-22 | 卡罗生物股份公司 | Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders |
US7279593B2 (en) | 2001-08-24 | 2007-10-09 | Karo Bio Ab | Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders |
US6723744B2 (en) | 2001-09-26 | 2004-04-20 | Pfizer, Inc. | Indole carboxylic acids as thyroid receptor ligands |
WO2003064369A1 (en) * | 2002-01-30 | 2003-08-07 | Kissei Pharmaceutical Co., Ltd. | Novel thyroid hormone receptor ligand, medicinal compositions containing the same and use thereof |
US7230031B2 (en) | 2002-01-30 | 2007-06-12 | Kissei Pharmaceutical Co., Ltd. | Thyroid hormone receptor ligand, medicinal compositions containing the same and use thereof |
WO2003084915A1 (en) * | 2002-04-11 | 2003-10-16 | Karo Bio Ab | Novel thyroid receptor ligands |
JP2005538076A (en) * | 2002-07-10 | 2005-12-15 | カロ バイオ アクチェブラーグ | Benzamide or phenylacetamide derivatives useful as thyroid receptor ligands |
US7153997B2 (en) | 2002-07-10 | 2006-12-26 | Karo Bio Ab | Benzamide derivatives as thyroid receptor ligands |
WO2004007430A3 (en) * | 2002-07-10 | 2004-02-19 | Karobio Ab | Benzamide or phenylacetamide derivatives useful as thyroid receptor ligands |
WO2004007430A2 (en) * | 2002-07-10 | 2004-01-22 | Karo Bio Ab | Benzamide or phenylacetamide derivatives useful as thyroid receptor ligands |
JP2006511474A (en) * | 2002-09-19 | 2006-04-06 | イーライ・リリー・アンド・カンパニー | Diaryl ethers as opioid receptor antagonists |
WO2004101495A1 (en) * | 2003-05-16 | 2004-11-25 | Procorde Gmbh | Compounds for use as a medicine increasing the contractility of a heart, a heart muscle or cells of a heart muscle |
EP1477475A1 (en) * | 2003-05-16 | 2004-11-17 | Procorde GmbH | Compounds for use as a medicine increasing the contractility of a heart, a heart muscle or cells of a heart muscle |
WO2005009433A1 (en) * | 2003-07-24 | 2005-02-03 | Fernando Goglia | Use of 3,5 diiodothyronine as regulators of lipid metabolism |
US7829552B2 (en) | 2003-11-19 | 2010-11-09 | Metabasis Therapeutics, Inc. | Phosphorus-containing thyromimetics |
US7795448B2 (en) | 2004-05-06 | 2010-09-14 | Cytokinetics, Incorporated | Imidazoyl-benzamide anti-cancer agents |
US7618981B2 (en) | 2004-05-06 | 2009-11-17 | Cytokinetics, Inc. | Imidazopyridinyl-benzamide anti-cancer agents |
US8772507B2 (en) | 2004-05-06 | 2014-07-08 | Cytokinetics, Inc. | Imidazole-benzamide anti-cancer agents |
US7504413B2 (en) | 2004-05-06 | 2009-03-17 | Cytokinetics, Inc. | N-(4-(imidazo[1,2A]pyridin-YL)phenethyl)benzamide inhibitors of the mitotic kinesin CENP-E for treating certain cellular proliferation diseases |
US8207340B2 (en) | 2004-05-06 | 2012-06-26 | Cytokinetics, Incorporated | Imidazopyridinyl benzamide mitotic kinesin inhibitors |
US8163919B2 (en) | 2004-05-06 | 2012-04-24 | Cytokinetics, Incorporated | Imidazopyridinyl benzamide mitotic kinesin inhibitors |
WO2005120477A3 (en) * | 2004-06-07 | 2006-03-02 | Merck & Co Inc | N- (2-benzyl) -2-phenylbutanamides as androgen receptor modulators |
US7629367B2 (en) | 2004-06-07 | 2009-12-08 | Merck & Co., Inc. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
US7763659B2 (en) | 2004-06-07 | 2010-07-27 | Merck Sharp & Dohme Corp. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
US7268153B2 (en) * | 2004-06-07 | 2007-09-11 | Merck & Co., Inc. | N-(2-benzyl)-2-phenylbutanamides as androgen receptor modulators |
WO2006076509A1 (en) | 2005-01-13 | 2006-07-20 | Bristol-Myers Squibb Company | Heterocyclic modulators of the glucocorticoid receptor, ap-1, and/or nf-kb activity and use thereof |
EP2527337A1 (en) | 2005-04-14 | 2012-11-28 | Bristol-Myers Squibb Company | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
US7521557B2 (en) | 2005-05-20 | 2009-04-21 | Bristol-Myers Squibb Company | Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods |
US10130643B2 (en) | 2005-05-26 | 2018-11-20 | Metabasis Therapeutics, Inc. | Thyromimetics for the treatment of fatty liver diseases |
US10925885B2 (en) | 2005-05-26 | 2021-02-23 | Metabasis Therapeutics, Inc. | Thyromimetics for the treatment of fatty liver diseases |
US7317012B2 (en) | 2005-06-17 | 2008-01-08 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoind-1 receptor modulators |
US7629342B2 (en) | 2005-06-17 | 2009-12-08 | Bristol-Myers Squibb Company | Azabicyclic heterocycles as cannabinoid receptor modulators |
US7452892B2 (en) | 2005-06-17 | 2008-11-18 | Bristol-Myers Squibb Company | Triazolopyrimidine cannabinoid receptor 1 antagonists |
US7632837B2 (en) | 2005-06-17 | 2009-12-15 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid-1 receptor modulators |
US7858639B2 (en) | 2005-06-17 | 2010-12-28 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid-1 receptor modulators |
WO2006138682A1 (en) | 2005-06-17 | 2006-12-28 | Bristol-Myers Squibb Company | Azabicyclic heterocycles as cannabinoid receptor modulators |
US7572808B2 (en) | 2005-06-17 | 2009-08-11 | Bristol-Myers Squibb Company | Triazolopyridine cannabinoid receptor 1 antagonists |
US8344029B2 (en) | 2005-07-19 | 2013-01-01 | Daiichi Sankyo Company, Limited | Substituted propanamide derivative and pharmaceutical composition containing the same |
EP1908466A1 (en) * | 2005-07-19 | 2008-04-09 | Daiichi Sankyo Company, Limited | Substituted propanamide derivative and pharmaceutical composition containing the same |
EP1908466A4 (en) * | 2005-07-19 | 2012-05-30 | Daiichi Sankyo Co Ltd | Substituted propanamide derivative and pharmaceutical composition containing the same |
WO2007018314A2 (en) * | 2005-08-10 | 2007-02-15 | Takeda Pharmaceutical Company Limited | Therapeutic agent for diabetes |
WO2007018314A3 (en) * | 2005-08-10 | 2007-07-05 | Takeda Pharmaceutical | Therapeutic agent for diabetes |
US7795436B2 (en) | 2005-08-24 | 2010-09-14 | Bristol-Myers Squibb Company | Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists |
US8618115B2 (en) | 2005-10-26 | 2013-12-31 | Bristol-Myers Squibb Company | Substituted thieno[3,2-d]pyrimidinones as MCHR1 antagonists and methods for using them |
EP2298776A1 (en) | 2005-10-26 | 2011-03-23 | Bristol-Myers Squibb Company | Thienopyrimidinone derivatives as melanin concentrating hormone receptor-1 antagonists |
EP2487154A1 (en) | 2005-10-31 | 2012-08-15 | Bristol-Myers Squibb Company | Pyrrolidinyl beta-amino amide-based inhibitors of dipeptidyl peptidase IV and methods |
WO2007053819A2 (en) | 2005-10-31 | 2007-05-10 | Bristol-Myers Squibb Company | Pyrrolidinyl beta-amino amide-based inhibitors of dipeptidyl peptidase iv and methods |
US7582668B2 (en) | 2005-11-09 | 2009-09-01 | Cytokinetics, Incorporated | Imidazoyl-benzamide anti-cancer agents |
US7956049B2 (en) | 2006-02-06 | 2011-06-07 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
US7553836B2 (en) | 2006-02-06 | 2009-06-30 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
WO2007120729A3 (en) * | 2006-04-12 | 2008-01-03 | Merck & Co Inc | Pyridyl amide t-type calcium channel antagonists |
AU2007238755B2 (en) * | 2006-04-12 | 2012-07-12 | Merck Sharp & Dohme Llc | Pyridyl amide T-type calcium channel antagonists |
US7875636B2 (en) | 2006-04-12 | 2011-01-25 | Merck Sharp & Dohme Corp. | Pyridyl amide T-type calcium channel antagonists |
WO2007120729A2 (en) * | 2006-04-12 | 2007-10-25 | Merck & Co., Inc. | Pyridyl amide t-type calcium channel antagonists |
WO2007120083A1 (en) * | 2006-04-13 | 2007-10-25 | Astrazeneca Ab | The use of carboxamide derivatives in the manufacture of a medicament for the treatment of inflammatory, allergic and dermatological conditions |
WO2007132475A1 (en) * | 2006-05-15 | 2007-11-22 | Cadila Healthcare Limited | Selective tr-beta 1 agonist |
WO2007139589A1 (en) | 2006-05-26 | 2007-12-06 | Bristol-Myers Squibb Company | Sustained release glp-1 receptor modulators |
EP2457918A2 (en) | 2006-06-28 | 2012-05-30 | Bristol-Myers Squibb Company | Crystalline solvates and complexes of (1s)-1,5-anhydro-1-c-(3-((phenyl) methyl) phenyl)-d-glucitol derivatives with amino acids as SGLT2 inhibitors for the treatment of diabetes |
EP3363807A1 (en) | 2006-06-28 | 2018-08-22 | AstraZeneca AB | Pharmaceutical composition comprising crystalline (2s,3r,4s,5s,6r)-2-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-6-hydroxymethyl-2-methoxy-tetrahydro-pyran-3,4,5-triol (s)-propylene glycol solvate |
EP3045466A1 (en) | 2006-06-28 | 2016-07-20 | AstraZeneca AB | (2s,3r,4s,5s,6r)-2-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-6-hydroxymethyl-2-methoxy-tetrahydro-pyran-3,4,5-triol propylene glycol solvate as sgt2 inhibitor for the treatment of diabetes |
EP2527317A1 (en) | 2006-08-24 | 2012-11-28 | Bristol-Myers Squibb Company | Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors |
WO2008057862A2 (en) | 2006-11-01 | 2008-05-15 | Bristol-Myers Squibb Company | MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-ϰB ACTIVITY AND USE THEREOF |
WO2008057857A1 (en) | 2006-11-01 | 2008-05-15 | Bristol-Myers Squibb Company | MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-ϰB ACTIVITY AND USE THEREOF |
US7931696B2 (en) | 2007-01-31 | 2011-04-26 | BASF SE Ludwigshafen | Cationic dyes |
WO2008092771A1 (en) * | 2007-01-31 | 2008-08-07 | Ciba Holding Inc. | Cationic dyes |
US8399518B2 (en) | 2007-02-27 | 2013-03-19 | University Of Arizona Office Of Technology Transfer | Administration of 3,5-diiodothyropropionic acid for stimulating weight loss, and/or lowering triglyceride levels, and/or treatment of metabolic syndrome |
EP4245299A2 (en) | 2007-03-22 | 2023-09-20 | Astrazeneca AB | Pharmaceutical formulations containing dapagliflozin propylene glycol hydrate |
EP2474549A1 (en) | 2007-04-17 | 2012-07-11 | Bristol-Myers Squibb Company | Fused heterocyclic 11-beta-hydroxysteroid dehydrogenase type I inhibitors |
US8236847B2 (en) | 2007-04-20 | 2012-08-07 | Bristol-Myers Squibb Company | Crystal forms of saxagliptin and processes for preparing same |
US7943656B2 (en) | 2007-04-20 | 2011-05-17 | Bristol-Myers Squibb Company | Crystal forms of saxagliptin and processes for preparing same |
US8802715B2 (en) | 2007-04-20 | 2014-08-12 | Astrazeneca Ab | Crystal forms of saxagliptin and processes for preparing same |
EP2481726A2 (en) | 2007-04-20 | 2012-08-01 | Bristol-Myers Squibb Company | Crystal forms of saxagliptin and processes for preparing same |
US8067420B2 (en) | 2007-07-06 | 2011-11-29 | Bristol-Myers Squibb Company | Substituted pyrazinone melanin concentrating hormone receptor-1 antagonists and methods |
US8012984B2 (en) | 2007-07-06 | 2011-09-06 | Bristol-Myers Squibb Company | Substituted pyrazinone melanin concentrating hormone receptor-1 antagonists and methods |
US7812048B2 (en) | 2007-07-27 | 2010-10-12 | Bristol-Myers Squibb Company | Glucokinase activators and methods of using same |
US8273777B2 (en) | 2007-07-27 | 2012-09-25 | Bristol-Meyer Squibb Company | Glucokinase activators and methods of using same |
WO2009058944A2 (en) | 2007-11-01 | 2009-05-07 | Bristol-Myers Squibb Company | Nonsteroidal compounds useful as modulators of glucocorticoid receptor ap-1 and /or nf- kappa b activity and use thereof |
WO2009080835A1 (en) * | 2007-12-24 | 2009-07-02 | Karo Bio Ab | Thyromimetric compounds in treatment of disease related to sonic hedgehog signalling |
US7989433B2 (en) | 2008-05-29 | 2011-08-02 | Bristol-Myers Squibb Company | Substituted thieno[3,2-D]pyrimidines as melanin concentrating hormone receptor-1 antagonists |
WO2010049946A2 (en) | 2008-10-27 | 2010-05-06 | Cadila Healthcare Limited | Thyroid receptor ligands |
US8835498B2 (en) | 2008-11-19 | 2014-09-16 | Pola Chemical Industries Inc. | Anti-wrinkle agents |
WO2010086878A2 (en) | 2009-01-09 | 2010-08-05 | Cadila Healthcare Limited | Thyroid receptor modulators |
WO2010111665A1 (en) | 2009-03-27 | 2010-09-30 | Bristol-Myers Squibb Company | Methods for preventing major adverse cardiovascular events with dpp-iv inhibitors |
EP2423194A4 (en) * | 2009-04-20 | 2012-10-24 | Mitsubishi Tanabe Pharma Corp | NOVEL THYROID HORMONE beta RECEPTOR AGONIST |
AU2010240200B2 (en) * | 2009-04-20 | 2014-03-13 | Mitsubishi Tanabe Pharma Corporation | Novel thyroid hormone beta receptor agonist |
US8791266B2 (en) | 2009-04-20 | 2014-07-29 | Mitsubishi Tanabe Pharma Corporation | Thyroid hormone β receptor agonist |
WO2010122980A1 (en) | 2009-04-20 | 2010-10-28 | 田辺三菱製薬株式会社 | Novel thyroid hormone β receptor agonist |
EP2423194A1 (en) * | 2009-04-20 | 2012-02-29 | Mitsubishi Tanabe Pharma Corporation | NOVEL THYROID HORMONE beta RECEPTOR AGONIST |
WO2011060256A2 (en) | 2009-11-13 | 2011-05-19 | Bristol-Myers Squibb Company | Bilayer tablet formulations |
EP3315124A1 (en) | 2009-11-13 | 2018-05-02 | Astrazeneca AB | Bilayer tablet formulations |
WO2011060255A1 (en) | 2009-11-13 | 2011-05-19 | Bristol-Myers Squibb Company | Reduced mass metformin formulations |
WO2011060290A2 (en) | 2009-11-13 | 2011-05-19 | Bristol-Myer Squibb Company | Immediate release tablet formulations |
WO2011103126A1 (en) * | 2010-02-17 | 2011-08-25 | Ampla Pharmaceuticals Inc. | Treatment of metabolic syndrome with piperidine amides |
WO2011130459A1 (en) | 2010-04-14 | 2011-10-20 | Bristol-Myers Squibb Company | Novel glucokinase activators and methods of using same |
US8772293B2 (en) | 2010-07-09 | 2014-07-08 | Pfizer Limited | Chemical compounds |
US8772343B2 (en) | 2010-07-12 | 2014-07-08 | Pfizer Limited | Chemical compounds |
US9096500B2 (en) | 2010-07-12 | 2015-08-04 | Pfizer Limited | Acyl sulfonamide compounds |
US9102621B2 (en) | 2010-07-12 | 2015-08-11 | Pfizer Limited | Acyl sulfonamide compounds |
US8685977B2 (en) | 2010-07-12 | 2014-04-01 | Pfizer Limited | Chemical compounds |
US8592629B2 (en) | 2010-07-12 | 2013-11-26 | Pfizer Limited | Sulfonamide derivatives as Nav 1.7 inhibitors |
US9481677B2 (en) | 2011-10-31 | 2016-11-01 | Xenon Pharmaceuticals Inc. | Biaryl ether sulfonamides and their use as therapeutic agents |
US9630929B2 (en) | 2011-10-31 | 2017-04-25 | Xenon Pharmaceuticals Inc. | Benzenesulfonamide compounds and their use as therapeutic agents |
US9085517B2 (en) | 2011-12-15 | 2015-07-21 | Pfizer Limited | Sulfonamide derivatives |
US10071957B2 (en) | 2012-07-06 | 2018-09-11 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
WO2014008458A3 (en) * | 2012-07-06 | 2014-04-17 | Genentech, Inc. | N-substituted benzamides and methods of use thereof |
CN104797555A (en) * | 2012-07-06 | 2015-07-22 | 基因泰克公司 | N-substituted benzamides and methods of use thereof |
US9586900B2 (en) | 2012-09-05 | 2017-03-07 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
US9499482B2 (en) | 2012-09-05 | 2016-11-22 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
WO2014039412A1 (en) | 2012-09-05 | 2014-03-13 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
US9550775B2 (en) | 2013-03-14 | 2017-01-24 | Genentech, Inc. | Substituted triazolopyridines and methods of use thereof |
US9493429B2 (en) | 2013-03-15 | 2016-11-15 | Genentech, Inc. | Substituted benzoxazoles and methods of use thereof |
WO2015027021A1 (en) | 2013-08-22 | 2015-02-26 | Bristol-Myers Squibb Company | Imide and acylurea derivatives as modulators of the glucocorticoid receptor |
US9546164B2 (en) | 2013-11-27 | 2017-01-17 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
US9694002B2 (en) | 2013-11-27 | 2017-07-04 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
US10526285B2 (en) | 2014-07-07 | 2020-01-07 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US11149002B2 (en) | 2014-07-07 | 2021-10-19 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US10125098B2 (en) | 2014-07-07 | 2018-11-13 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US10005724B2 (en) | 2014-07-07 | 2018-06-26 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US10179767B2 (en) | 2015-05-22 | 2019-01-15 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
US11130726B2 (en) | 2015-08-27 | 2021-09-28 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US10787446B2 (en) | 2015-09-28 | 2020-09-29 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US10899732B2 (en) | 2015-11-25 | 2021-01-26 | Genentech, Inc. | Substituted benzamides useful as sodium channel blockers |
US11203572B2 (en) | 2016-03-30 | 2021-12-21 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
US10766858B2 (en) | 2016-03-30 | 2020-09-08 | Genentech, Inc. | Substituted benzamides and methods of use thereof |
EP3445749B1 (en) * | 2016-04-18 | 2022-12-21 | Novartis AG | Compounds and compositions for treating conditions associated with nlrp activity |
US11447460B2 (en) | 2016-04-18 | 2022-09-20 | Novartis Ag | Compounds and compositions for treating conditions associated with NLRP activity |
US11325886B2 (en) | 2016-08-12 | 2022-05-10 | Oregon Health & Science University | Amide compounds, pharmaceutical compositions thereof, and methods of using the same |
IL264765B1 (en) * | 2016-08-12 | 2023-11-01 | Univ Oregon Health & Science | Amide compounds, pharmaceutical compositions thereof, and methods of using the same |
EP3497077A4 (en) * | 2016-08-12 | 2020-01-22 | Oregon Health & Science University | Amide compounds, pharmaceutical compositions thereof, and methods of using the same |
AU2017310535B2 (en) * | 2016-08-12 | 2021-11-11 | Oregon Health & Science University | Amide compounds, pharmaceutical compositions thereof, and methods of using the same |
RU2759913C2 (en) * | 2016-08-12 | 2021-11-18 | Орегон Хэлт Энд Сайенс Юниверсити | Amide compounds, pharmaceutical compositions containing them and their application methods |
IL264765B2 (en) * | 2016-08-12 | 2024-03-01 | Univ Oregon Health & Science | Amide compounds, pharmaceutical compositions thereof, and methods of using the same |
US10457654B2 (en) | 2016-10-17 | 2019-10-29 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US11202789B2 (en) | 2016-11-21 | 2021-12-21 | Viking Therapeutics, Inc. | Method of treating glycogen storage disease |
US11707472B2 (en) | 2017-06-05 | 2023-07-25 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis |
WO2019054514A1 (en) | 2017-09-14 | 2019-03-21 | 国立研究開発法人理化学研究所 | Method for producing retinal tissues |
US11718631B2 (en) | 2017-10-17 | 2023-08-08 | Novartis Ag | Sulphonamides and compositions thereof for treating conditions associated with NLRP activity |
WO2019079119A1 (en) * | 2017-10-17 | 2019-04-25 | IFM Tre, Inc. | Sulphonamides and compositions thereof for treating conditions associated with nlrp activity |
US11752173B2 (en) | 2017-12-19 | 2023-09-12 | Beijing Jiyuan Biological Technology Co., Ltd. | FGF21 and GLP1 double gene-modified mesenchymal stem cell and use in treating a metabolic disease |
US11028075B2 (en) | 2018-02-26 | 2021-06-08 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
US11787828B2 (en) | 2018-03-22 | 2023-10-17 | Viking Therapeutics, Inc. | Crystalline forms and methods of producing crystalline forms of a compound |
US10947251B2 (en) | 2018-03-30 | 2021-03-16 | Genentech, Inc. | Therapeutic compounds and methods of use thereof |
WO2020016335A1 (en) | 2018-07-19 | 2020-01-23 | Astrazeneca Ab | Methods of treating hfpef employing dapagliflozin and compositions comprising the same |
US12102646B2 (en) | 2018-12-05 | 2024-10-01 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis and inflammation |
US11827596B2 (en) | 2018-12-12 | 2023-11-28 | Autobahn Therapeutics, Inc. | Thyromimetics |
US11667606B2 (en) | 2019-03-01 | 2023-06-06 | Autobahn Therapeutics, Inc. | Thyromimetics |
WO2020184720A1 (en) | 2019-03-13 | 2020-09-17 | 大日本住友製薬株式会社 | Method for evaluating quality of transplant neural retina, and transplant neural retina sheet |
WO2022054924A1 (en) | 2020-09-11 | 2022-03-17 | 大日本住友製薬株式会社 | Medium for tissue for transplantation |
WO2022054925A1 (en) | 2020-09-11 | 2022-03-17 | 国立研究開発法人理化学研究所 | Complex containing neural retina-containing cell aggregates and matrix, and method for manufacturing same |
WO2023090427A1 (en) | 2021-11-19 | 2023-05-25 | 国立研究開発法人理化学研究所 | Production method for sheet-like retinal tissue |
Also Published As
Publication number | Publication date |
---|---|
ID29013A (en) | 2001-07-26 |
CA2356319A1 (en) | 2000-07-06 |
ZA200104932B (en) | 2003-01-15 |
WO2000039077A3 (en) | 2000-09-21 |
IL143799A0 (en) | 2002-04-21 |
KR20010108032A (en) | 2001-12-07 |
US6989402B1 (en) | 2006-01-24 |
HUP0104666A2 (en) | 2002-03-28 |
AU1885500A (en) | 2000-07-31 |
JP4405088B2 (en) | 2010-01-27 |
RU2001120701A (en) | 2003-12-10 |
CN1337953A (en) | 2002-02-27 |
NZ512422A (en) | 2004-02-27 |
CN1186332C (en) | 2005-01-26 |
US7288571B2 (en) | 2007-10-30 |
NO20012931D0 (en) | 2001-06-13 |
HUP0104666A3 (en) | 2003-05-28 |
JP2002533432A (en) | 2002-10-08 |
US20050282872A1 (en) | 2005-12-22 |
EP1144370A2 (en) | 2001-10-17 |
TR200101834T2 (en) | 2001-12-21 |
CZ20012204A3 (en) | 2001-11-14 |
AU758202B2 (en) | 2003-03-20 |
GB9828442D0 (en) | 1999-02-17 |
NO20012931L (en) | 2001-08-21 |
BR9916851A (en) | 2001-10-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4405088B2 (en) | Novel thyroid receptor ligands and method II | |
AU735525B2 (en) | Novel thyroid receptor ligands and method | |
US7109164B2 (en) | Aniline-derived ligands for the thyroid receptor | |
CN1056141C (en) | Piperazine derivatives | |
SK283201B6 (en) | Nitric oxide synthase inhibitors | |
CA2493660A1 (en) | Process for preparing quinolin antibiotic intermediates | |
EP0457163A1 (en) | Use of oxyl-aminoacid derivatives as drug for inhibiting the prolyl-hydroxylase | |
IE48072B1 (en) | Derivatives of dehydrocyclicimino acids | |
JPS58177934A (en) | Benzoquinone derivative | |
JPH0755927B2 (en) | Cholecystokinin (CCK) antagonist | |
WO1994015908A1 (en) | Propionamide derivative and medicinal use thereof | |
JPH0564948B2 (en) | ||
AU624978B2 (en) | N,n'-bis(alkoxyalkyl)-pyridine-2,4-dicarboxylic acid diamides, preparation and their use | |
EP0333000B1 (en) | Peptides with inhibitory activity of enzymatic systems, process for their preparation and pharmaceutical compositions containing them | |
EP0636621B1 (en) | Beta-mercapto-propanamide derivatives useful in the treatment of cardiovascular diseases | |
MXPA01006482A (en) | Novel thyroid receptor ligands and method ii | |
US6063964A (en) | 5-hydroxymethyl-2-aminotetralins as cardiovascular agents | |
US6066672A (en) | Amino compounds and angiotensin IV receptor agonists | |
JPH0523259B2 (en) | ||
DE69614508T2 (en) | THIOL DERIVATIVES WITH ACTIVITY INHIBITING METALLOPEPTIDASE | |
US20020161030A1 (en) | Sulpur derivatives containing a retroamide bond as inhibitors of endothelin-converting enzymes | |
JP2003533506A5 (en) | N-substituted peptidyl nitriles as cysteine cathepsin inhibitors | |
US20220289668A1 (en) | N-formylhydroxylamines as neprilysin (nep) inhibitors, in particular as mixed aminopeptidase n (apn) and neprilysin (nep) inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
WWE | Wipo information: entry into national phase |
Ref document number: 99815057.6 Country of ref document: CN |
|
AK | Designated states |
Kind code of ref document: A2 Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM 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 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: A2 Designated state(s): GH GM KE LS MW 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 BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
AK | Designated states |
Kind code of ref document: A3 Designated state(s): AE AL AM AT AU AZ BA BB BG BR BY CA CH CN CR CU CZ DE DK DM 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 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: A3 Designated state(s): GH GM KE LS MW 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 BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG |
|
WWE | Wipo information: entry into national phase |
Ref document number: 18855/00 Country of ref document: AU |
|
WWE | Wipo information: entry into national phase |
Ref document number: 200104932 Country of ref document: ZA Ref document number: 512422 Country of ref document: NZ |
|
WWE | Wipo information: entry into national phase |
Ref document number: 143799 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: PV2001-2204 Country of ref document: CZ |
|
ENP | Entry into the national phase |
Ref document number: 2356319 Country of ref document: CA Ref document number: 2356319 Country of ref document: CA Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1020017007766 Country of ref document: KR |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2001/01834 Country of ref document: TR |
|
WWE | Wipo information: entry into national phase |
Ref document number: PA/a/2001/006482 Country of ref document: MX |
|
ENP | Entry into the national phase |
Ref document number: 2000 590990 Country of ref document: JP Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 1999962486 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: IN/PCT/2001/754/KOL Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 09868889 Country of ref document: US |
|
WWP | Wipo information: published in national office |
Ref document number: 1999962486 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: PV2001-2204 Country of ref document: CZ |
|
WWP | Wipo information: published in national office |
Ref document number: 1020017007766 Country of ref document: KR |
|
WWG | Wipo information: grant in national office |
Ref document number: 18855/00 Country of ref document: AU |
|
WWR | Wipo information: refused in national office |
Ref document number: 1020017007766 Country of ref document: KR |