EA015324B1 - Способы и соединения для получения аналогов сс-1065 - Google Patents
Способы и соединения для получения аналогов сс-1065 Download PDFInfo
- Publication number
- EA015324B1 EA015324B1 EA200801176A EA200801176A EA015324B1 EA 015324 B1 EA015324 B1 EA 015324B1 EA 200801176 A EA200801176 A EA 200801176A EA 200801176 A EA200801176 A EA 200801176A EA 015324 B1 EA015324 B1 EA 015324B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- alkyl
- group
- tert
- substituted
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 134
- 238000000034 method Methods 0.000 title claims abstract description 37
- -1 CBI CC-1065 analog Chemical class 0.000 claims abstract description 104
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 52
- 125000003118 aryl group Chemical group 0.000 claims abstract description 41
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 32
- 125000006239 protecting group Chemical group 0.000 claims abstract description 27
- 150000001412 amines Chemical class 0.000 claims abstract description 15
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 7
- 238000000926 separation method Methods 0.000 claims abstract description 7
- 125000003277 amino group Chemical group 0.000 claims abstract description 6
- 230000029936 alkylation Effects 0.000 claims abstract description 4
- 238000005804 alkylation reaction Methods 0.000 claims abstract description 4
- 230000007062 hydrolysis Effects 0.000 claims abstract 2
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract 2
- 125000000217 alkyl group Chemical group 0.000 claims description 59
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 56
- 230000015572 biosynthetic process Effects 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002367 halogens Chemical class 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 7
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000005544 phthalimido group Chemical group 0.000 claims description 4
- 230000002152 alkylating effect Effects 0.000 claims description 3
- 230000026045 iodination Effects 0.000 claims description 3
- 238000006192 iodination reaction Methods 0.000 claims description 3
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 3
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 3
- ROORDVPLFPIABK-UHFFFAOYSA-N diphenyl carbonate Chemical group C=1C=CC=CC=1OC(=O)OC1=CC=CC=C1 ROORDVPLFPIABK-UHFFFAOYSA-N 0.000 claims 2
- 238000003821 enantio-separation Methods 0.000 claims 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 2
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- YEDXNNZSFJWVOF-UHFFFAOYSA-N methyl(phenylmethoxymethylidene)oxidanium Chemical compound C\[O+]=[C-]\OCc1ccccc1 YEDXNNZSFJWVOF-UHFFFAOYSA-N 0.000 claims 1
- UOWVMDUEMSNCAV-WYENRQIDSA-N rachelmycin Chemical compound C1([C@]23C[C@@H]2CN1C(=O)C=1NC=2C(OC)=C(O)C4=C(C=2C=1)CCN4C(=O)C1=CC=2C=4CCN(C=4C(O)=C(C=2N1)OC)C(N)=O)=CC(=O)C1=C3C(C)=CN1 UOWVMDUEMSNCAV-WYENRQIDSA-N 0.000 abstract description 13
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000000543 intermediate Substances 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 239000011541 reaction mixture Substances 0.000 description 35
- 239000000243 solution Substances 0.000 description 33
- 150000001413 amino acids Chemical class 0.000 description 31
- 235000001014 amino acid Nutrition 0.000 description 30
- 125000001072 heteroaryl group Chemical group 0.000 description 27
- 238000003786 synthesis reaction Methods 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 125000004404 heteroalkyl group Chemical group 0.000 description 23
- 125000001424 substituent group Chemical group 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 21
- 239000003814 drug Substances 0.000 description 21
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 19
- 229940079593 drug Drugs 0.000 description 17
- KTLUMOZOWZSJFC-UHFFFAOYSA-N 3-azatetracyclo[7.5.0.02,6.012,14]tetradeca-1,3,5,7,9,11,13-heptaene Chemical class C1=C2C=CN=C2C2=C3C=C3C=CC2=C1 KTLUMOZOWZSJFC-UHFFFAOYSA-N 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- 150000003254 radicals Chemical class 0.000 description 16
- 239000007858 starting material Substances 0.000 description 15
- 239000003921 oil Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000012634 fragment Substances 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000000427 antigen Substances 0.000 description 10
- 102000036639 antigens Human genes 0.000 description 10
- 108091007433 antigens Proteins 0.000 description 10
- 239000000562 conjugate Substances 0.000 description 10
- 125000005647 linker group Chemical group 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 125000000547 substituted alkyl group Chemical group 0.000 description 9
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- 239000012267 brine Substances 0.000 description 8
- 230000021615 conjugation Effects 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
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- 125000003107 substituted aryl group Chemical group 0.000 description 7
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/58—[b]- or [c]-condensed
- C07D209/60—Naphtho [b] pyrroles; Hydrogenated naphtho [b] pyrroles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US73080405P | 2005-10-26 | 2005-10-26 | |
| PCT/US2006/060050 WO2007051081A1 (en) | 2005-10-26 | 2006-10-18 | Methods and compounds for preparing cc-1065 analogs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA200801176A1 EA200801176A1 (ru) | 2009-02-27 |
| EA015324B1 true EA015324B1 (ru) | 2011-06-30 |
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|---|---|---|---|
| EA200801176A EA015324B1 (ru) | 2005-10-26 | 2006-10-18 | Способы и соединения для получения аналогов сс-1065 |
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| MX2009007987A (es) | 2007-01-25 | 2010-03-01 | Dana Farber Cancer Inst Inc | Uso de anticuerpos anti-egfr en el tratamiento de enfermedad mediada por egfr mutante. |
| US9023356B2 (en) | 2007-03-15 | 2015-05-05 | Ludwig Institute For Cancer Research Ltd | Treatment method using EGFR antibodies and SRC inhibitors and related formulations |
| US9901567B2 (en) | 2007-08-01 | 2018-02-27 | Syntarga B.V. | Substituted CC-1065 analogs and their conjugates |
| JP5532486B2 (ja) | 2007-08-14 | 2014-06-25 | ルードヴィッヒ インスティテュート フォー キャンサー リサーチ | Ｅｇｆ受容体を標的とするモノクローナル抗体１７５ならびにその誘導体および用途 |
| EP2185188B1 (en) | 2007-08-22 | 2014-08-06 | Medarex, L.L.C. | Site-specific attachment of drugs or other agents to engineered antibodies with c-terminal extensions |
| CA2700860C (en) * | 2007-10-01 | 2016-07-19 | Jonathan A. Terrett | Human antibodies that bind mesothelin, and uses thereof |
| AR072999A1 (es) | 2008-08-11 | 2010-10-06 | Medarex Inc | Anticuerpos humanos que se unen al gen 3 de activacion linfocitaria (lag-3) y los usos de estos |
| MX2011004625A (es) | 2008-11-03 | 2011-07-20 | Syntarga Bv | Analogos cc-1065 novedosos y sus conjugados. |
| WO2010096394A2 (en) | 2009-02-17 | 2010-08-26 | Redwood Biosciences, Inc. | Aldehyde-tagged protein-based drug carriers and methods of use |
| PL2403878T3 (pl) | 2009-03-05 | 2017-12-29 | E. R. Squibb & Sons, L.L.C. | W pełni ludzkie przeciwciała specyficzne dla CADM1 |
| US8394922B2 (en) | 2009-08-03 | 2013-03-12 | Medarex, Inc. | Antiproliferative compounds, conjugates thereof, methods therefor, and uses thereof |
| PL2560645T3 (pl) | 2010-04-21 | 2017-01-31 | Syntarga B.V. | Koniugaty analogów CC-1065 i łączników dwufunkcyjnych |
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| PE20141791A1 (es) | 2012-02-13 | 2014-11-19 | Bristol Myers Squibb Co | Compuestos de enediino, conjugados de los mismos y sus usos y metodos |
| UY34887A (es) | 2012-07-02 | 2013-12-31 | Bristol Myers Squibb Company Una Corporacion Del Estado De Delaware | Optimización de anticuerpos que se fijan al gen de activación de linfocitos 3 (lag-3) y sus usos |
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| SG10201911860VA (en) | 2014-01-10 | 2020-02-27 | Synthon Biopharmaceuticals Bv | Duocarmycin adcs showing improved in vivo antitumor activity |
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| MX368234B (es) | 2014-01-10 | 2019-09-25 | Synthon Biopharmaceuticals Bv | Conjugados de anticuerpo-fármaco (adcs) que contienen duocarmicina para usarse en el tratamiento de cáncer endometrial. |
| EP3647322B1 (en) | 2014-03-20 | 2021-10-20 | Bristol-Myers Squibb Company | Stabilized fibronectin based scaffold molecules |
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| US10077287B2 (en) | 2014-11-10 | 2018-09-18 | Bristol-Myers Squibb Company | Tubulysin analogs and methods of making and use |
| KR102569813B1 (ko) | 2014-11-21 | 2023-08-24 | 브리스톨-마이어스 스큅 컴퍼니 | Cd73에 대항한 항체 및 그의 용도 |
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| CN107207379B (zh) | 2014-11-25 | 2021-08-10 | 百时美施贵宝公司 | 用于生物制品的18f-放射性标记的方法和组合物 |
| ES2822990T3 (es) | 2014-11-25 | 2021-05-05 | Bristol Myers Squibb Co | Novedosos polipéptidos de unión a PD-L1 para obtención de imágenes |
| WO2016097865A1 (en) | 2014-12-19 | 2016-06-23 | Regenesance B.V. | Antibodies that bind human c6 and uses thereof |
| MX2017009144A (es) | 2015-01-14 | 2017-11-22 | Bristol Myers Squibb Co | Dimeros de benzodiazepina unidos con puentes de heteroarileno, conjugados de estos, y sus metodos de preparacion y uso. |
| ES2809125T3 (es) | 2015-09-23 | 2021-03-03 | Bristol Myers Squibb Co | Moléculas de armazón a base de fibronectina de unión a glipicano-3 |
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| WO2007051081A1 (en) | 2007-05-03 |
| JP2009513676A (ja) | 2009-04-02 |
| JP5116686B2 (ja) | 2013-01-09 |
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| CN101365679B (zh) | 2012-11-14 |
| EP1940789B1 (en) | 2011-11-23 |
| PT1940789E (pt) | 2012-02-01 |
| PL1940789T3 (pl) | 2012-04-30 |
| BRPI0619331A2 (pt) | 2011-09-27 |
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| US20080281102A1 (en) | 2008-11-13 |
| SI1940789T1 (sl) | 2012-03-30 |
| CY1112533T1 (el) | 2015-12-09 |
| ATE534629T1 (de) | 2011-12-15 |
| US7847105B2 (en) | 2010-12-07 |
| KR20080068084A (ko) | 2008-07-22 |
| IL190971A0 (en) | 2008-12-29 |
| AU2006305842A1 (en) | 2007-05-03 |
| EP1940789A1 (en) | 2008-07-09 |
| ZA200804521B (en) | 2009-04-29 |
| WO2007051081A8 (en) | 2010-12-16 |
| EA200801176A1 (ru) | 2009-02-27 |
| DK1940789T3 (da) | 2012-03-19 |
| WO2007051081B1 (en) | 2007-07-19 |
| NO20082243L (no) | 2008-07-21 |
| RS52100B (en) | 2012-06-30 |
| CN101365679A (zh) | 2009-02-11 |
| CA2627046A1 (en) | 2007-05-03 |
| HRP20120058T1 (hr) | 2012-02-29 |
| CA2627046C (en) | 2015-09-15 |
| IL190971A (en) | 2013-02-28 |
| ES2375843T3 (es) | 2012-03-06 |
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