EA020409B1 - Антагонисты рецептора cgrp - Google Patents
Антагонисты рецептора cgrp Download PDFInfo
- Publication number
- EA020409B1 EA020409B1 EA201270561A EA201270561A EA020409B1 EA 020409 B1 EA020409 B1 EA 020409B1 EA 201270561 A EA201270561 A EA 201270561A EA 201270561 A EA201270561 A EA 201270561A EA 020409 B1 EA020409 B1 EA 020409B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- pyridin
- tetrahydro
- difluorophenyl
- cyclohepta
- hydrogen
- Prior art date
Links
- 239000002464 receptor antagonist Substances 0.000 title abstract description 5
- 229940044551 receptor antagonist Drugs 0.000 title abstract description 5
- 108010078311 Calcitonin Gene-Related Peptide Receptors Proteins 0.000 title abstract 2
- 102000008323 calcitonin gene-related peptide receptor activity proteins Human genes 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 79
- 238000000034 method Methods 0.000 claims abstract description 29
- 150000003839 salts Chemical class 0.000 claims abstract description 22
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- 206010027599 migraine Diseases 0.000 claims abstract description 15
- 239000000203 mixture Substances 0.000 claims description 139
- 229910052739 hydrogen Inorganic materials 0.000 claims description 95
- 239000001257 hydrogen Substances 0.000 claims description 95
- -1 hydroxy, azido, amino Chemical group 0.000 claims description 69
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 65
- 150000002431 hydrogen Chemical class 0.000 claims description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 21
- LOGAFLFGWNBIIG-UHFFFAOYSA-N pyridin-3-ylcarbamic acid Chemical compound OC(=O)NC1=CC=CN=C1 LOGAFLFGWNBIIG-UHFFFAOYSA-N 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 7
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 5
- 230000001594 aberrant effect Effects 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 229940125904 compound 1 Drugs 0.000 claims 1
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- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
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- 230000008092 positive effect Effects 0.000 description 1
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- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
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- 230000001681 protective effect Effects 0.000 description 1
- QZDWODWEESGPLC-UHFFFAOYSA-N pyridin-3-yl acetate Chemical compound CC(=O)OC1=CC=CN=C1 QZDWODWEESGPLC-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
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- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
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- 229910052710 silicon Inorganic materials 0.000 description 1
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- 239000002356 single layer Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- 150000003509 tertiary alcohols Chemical class 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- VHKIEYIESYMHPT-UHFFFAOYSA-N triethyl(methoxycarbonylsulfamoyl)azanium;hydroxide Chemical class [OH-].CC[N+](CC)(CC)S(=O)(=O)NC(=O)OC VHKIEYIESYMHPT-UHFFFAOYSA-N 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
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- A61P9/00—Drugs for disorders of the cardiovascular system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/20—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Heart & Thoracic Surgery (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
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| US25147709P | 2009-10-14 | 2009-10-14 | |
| PCT/US2010/052433 WO2011046997A1 (en) | 2009-10-14 | 2010-10-13 | Cgrp receptor antagonists |
Publications (2)
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| EA201270561A1 EA201270561A1 (ru) | 2012-12-28 |
| EA020409B1 true EA020409B1 (ru) | 2014-10-30 |
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| EA201270561A EA020409B1 (ru) | 2009-10-14 | 2010-10-13 | Антагонисты рецептора cgrp |
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| US8314117B2 (en) * | 2009-10-14 | 2012-11-20 | Bristol-Myers Squibb Company | CGRP receptor antagonists |
| US8669368B2 (en) * | 2010-10-12 | 2014-03-11 | Bristol-Myers Squibb Company | Process for the preparation of cycloheptapyridine CGRP receptor antagonists |
| US8748429B2 (en) * | 2011-04-12 | 2014-06-10 | Bristol-Myers Squibb Company | CGRP receptor antagonists |
| ES2746031T3 (es) * | 2012-02-27 | 2020-03-04 | Bristol Myers Squibb Co | Sal de N-(5S,6S,9R)-5-amino-6-(2,3-difluorofenil)-6,7,8,9-tetrahidro-5H-ciclohepta[B]piridin-9-IL-4-(2-oxo-2,3-dihidro-1H-imidazo[4,5-B]piridin-1-il)piperidina-1-carboxilato |
| EP2846801B1 (en) * | 2012-05-09 | 2017-04-05 | Merck Sharp & Dohme Corp. | Pyridine cgrp receptor antagonists |
| EP2815749A1 (en) | 2013-06-20 | 2014-12-24 | IP Gesellschaft für Management mbH | Solid form of 4-amino-2-(2,6-dioxopiperidine-3-yl)isoindoline-1,3-dione having specified X-ray diffraction pattern |
| TW201718574A (zh) * | 2015-08-12 | 2017-06-01 | 美國禮來大藥廠 | Ｃｇｒｐ受體拮抗劑 |
| GB201519195D0 (en) | 2015-10-30 | 2015-12-16 | Heptares Therapeutics Ltd | CGRP Receptor Antagonists |
| GB201519196D0 (en) | 2015-10-30 | 2015-12-16 | Heptares Therapeutics Ltd | CGRP Receptor Antagonists |
| GB201519194D0 (en) | 2015-10-30 | 2015-12-16 | Heptares Therapeutics Ltd | CGRP receptor antagonists |
| GB201707938D0 (en) | 2017-05-17 | 2017-06-28 | Univ Sheffield | Compounds |
| SG11202009199YA (en) | 2018-03-25 | 2020-10-29 | Biohaven Pharm Holding Co Ltd | Rimegepant for cgrp related disorders |
| CN114805206B (zh) * | 2021-01-27 | 2025-01-14 | 奥锐特药业(天津)有限公司 | 高光学纯度瑞美吉泮中间体的工业化制备方法 |
| EP4301362A1 (en) | 2021-03-02 | 2024-01-10 | CGRP Diagnostics GmbH | Treatment and/or reduction of occurrence of migraine |
| US20250109188A1 (en) | 2021-08-24 | 2025-04-03 | Cgrp Diagnostics Gmbh | Preventative treatment of migraine |
| CN115850266A (zh) * | 2021-09-26 | 2023-03-28 | 奥锐特药业(天津)有限公司 | 瑞美吉泮新晶型及其制备方法 |
| CN116554164B (zh) * | 2022-01-27 | 2025-10-03 | 奥锐特药业(天津)有限公司 | 一种瑞美吉泮的制备方法 |
| WO2023175632A1 (en) * | 2022-03-17 | 2023-09-21 | Msn Laboratories Private Limited, R&D Center | Solid state forms of (5s,6s,9r)-5-amino-6-(2,3difluorophenyl)-6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1h-imidazo[4,5-b]pyridin-1-yl)-1-piperidinecarboxylate hemisulfate and processes for preparation thereof |
| CN116478211B (zh) * | 2022-04-19 | 2023-10-24 | 石家庄迪斯凯威医药科技有限公司 | 一种新型cgrp受体拮抗剂及其用途 |
| CN115060824B (zh) * | 2022-06-14 | 2024-03-12 | 浙江宏元药业股份有限公司 | 一种瑞米吉泮中间体对映异构体杂质的液相色谱检测方法 |
| WO2024022434A1 (zh) * | 2022-07-29 | 2024-02-01 | 熙源安健医药（上海）有限公司 | 吡啶并环庚烷类衍生物及其制备方法和用途 |
| CN115677694A (zh) * | 2022-11-30 | 2023-02-03 | 南通常佑药业科技有限公司 | 一种瑞美吉泮的合成方法 |
| WO2024180562A1 (en) * | 2023-03-02 | 2024-09-06 | Natco Pharma Limited | A process for the preparation of pure crystalline rimegepant and its salts thereof |
| CN116768938B (zh) * | 2023-05-17 | 2025-11-11 | 南京艾德凯腾生物医药有限责任公司 | 一种铁催化剂及瑞美吉泮中间体的制备方法 |
| CN119661518A (zh) * | 2023-09-21 | 2025-03-21 | 成都康弘药业集团股份有限公司 | 一种治疗cgrp相关障碍的小分子药物 |
| CN117486798B (zh) * | 2023-12-21 | 2025-02-07 | 南京威凯尔生物医药科技有限公司 | 一种瑞美吉泮中间体盐酸盐的晶型及其制备方法 |
| WO2025193980A2 (en) * | 2024-03-13 | 2025-09-18 | CNS Biosciences, Inc. | Method of treating neuropathic pain using an anti-cgrp inhibitor |
| CN119707808B (zh) * | 2024-12-23 | 2025-12-05 | 上海彩迩文生化科技有限公司 | 一种制备cgrp受体拮抗剂中间体的方法 |
| CN119977885A (zh) * | 2025-04-15 | 2025-05-13 | 常州制药厂有限公司 | (5S,6S,9R)-5-氨基-6-(2,3-二氟苯基)-6,7,8,9-四氢-5H-环庚[b]吡啶-9-醇L-酒石酸盐及其制备方法 |
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| WO2006044504A1 (en) * | 2004-10-13 | 2006-04-27 | Merck & Co., Inc. | Cgrp receptor antagonists |
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| WO2009126530A2 (en) * | 2008-04-11 | 2009-10-15 | Bristol-Myers Squibb Company | Cgrp receptor antagonists |
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| JO2355B1 (en) * | 2003-04-15 | 2006-12-12 | ميرك شارب اند دوم كوربوريشن | Hereditary calcitonin polypeptide receptor antagonists |
| US20060084708A1 (en) | 2004-10-14 | 2006-04-20 | Bayer Materialscience Llc | Rigid foams with good insulation properties and a process for the production of such foams |
| EP2007763A2 (en) | 2006-04-10 | 2008-12-31 | Merck & Co., Inc. | Process for the preparation of pyridine heterocycle cgrp antagonist intermediate |
| US8143403B2 (en) | 2008-04-11 | 2012-03-27 | Bristol-Myers Squibb Company | CGRP receptor antagonists |
| US8314117B2 (en) * | 2009-10-14 | 2012-11-20 | Bristol-Myers Squibb Company | CGRP receptor antagonists |
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| EP1726590A1 (en) * | 2004-03-05 | 2006-11-29 | Banyu Pharmaceutical Co., Ltd. | Cycloalkanopyridine derivative |
| WO2006044504A1 (en) * | 2004-10-13 | 2006-04-27 | Merck & Co., Inc. | Cgrp receptor antagonists |
| WO2006047196A2 (en) * | 2004-10-22 | 2006-05-04 | Merck & Co., Inc. | Cgrp receptor antagonists |
| WO2009126530A2 (en) * | 2008-04-11 | 2009-10-15 | Bristol-Myers Squibb Company | Cgrp receptor antagonists |
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