ES2644758T3 - Moduladores de PKM2 y métodos para su uso - Google Patents
Moduladores de PKM2 y métodos para su uso Download PDFInfo
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- ES2644758T3 ES2644758T3 ES13847643.7T ES13847643T ES2644758T3 ES 2644758 T3 ES2644758 T3 ES 2644758T3 ES 13847643 T ES13847643 T ES 13847643T ES 2644758 T3 ES2644758 T3 ES 2644758T3
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
- A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
- C07D231/16—Halogen atoms or nitro radicals
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- C07D—HETEROCYCLIC COMPOUNDS
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- 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
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- 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
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- 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
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- 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
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- 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
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
- C07F9/6503—Five-membered rings
- C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2
Description
o un estereoisómero, sal farmacéuticamente aceptable, tautómero o profármaco del mismo, en donde: R7 y R8 son cada uno independientemente H, alquilo, alcoxi, halo, hidroxilo, hidroxialquilo, amino, aminoalquilo,
5 alquilaminoalquilo, nitrilo, nitro, -O(CH2)mP(=O)(OH)2, éster de aminoácido; y w es 1 o2. Por ejemplo, en algunas realizaciones del compuesto de estructura (I) tiene la siguiente estructura (la):
10 o un estereoisómero, sal farmacéuticamente aceptable, tautómero o profármaco del mismo, en donde: R15 es halo; R16 es H oNH2; y w es 1 o2.
15 En algunas realizaciones de estructura (la), R15 es cloro. En otras realizaciones, R15 es flúor. En algunas otras realizaciones de estructura (la), R16 es H. En otras realizaciones, R16 es NH2. En aún otras realizaciones de estructura (la), w es 1. En otras realizaciones, w es 2. En otras realizaciones específicas de estructura (I), el compuesto tiene la siguiente estructura (Ib'):
o un estereoisómero, sal farmacéuticamente aceptable, tautómero o profármaco del mismo, en dondee: Q es CH2 , O, NR13 , CF2 , o S(O)w;
5 R7 y R8 son cada uno independientemente H, alquilo, alcoxi, halo, hidroxilo, hidroxialquilo, amino, aminoalquilo, alquilaminoalquilo, nitrilo, nitro, -O (CH2)mP(=O)(OH)2, éster de aminoácido; R9, R11 y R13 son cada uno independientemente H o alquilo; R10 es H, hidroxilo, halo, alcoxi o alquilo; w es 0, 1o 2; y 10 tes1,2o3. Por ejemplo, en otras realizaciones específicas de estructura (I), el compuesto tiene la siguiente estructura (Ib):
o un estereoisómero, sal farmacéuticamente aceptable, tautómero o profármaco del mismo,
15 en donde: R7 es halo; R18 es H oNH2; Z es CH2, O, NH, NR19, CHR20 o CF2; R19 es alquilo;
20 R20 es alcoxi, hidroxilo o halo; y xes 0, 1, 2 o3. Por ejemplo, en algunas realizaciones, R17 es cloro. En otras realizaciones, R18 es NH2. En todavía otras realizaciones de estructura (lb), Z es CHOH. En otras realizaciones, Z es CHOCH3. En más
realizaciones, Z es CHF, y en otras realizaciones Z es O.
Tabla 1
Compuestos ilustrativos
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 1
-
imagen20 1H-RMN (CDCl3/400 MHz): 7,10 (m, 1H), 6,80 (m, 1H), 6,59 (d, J= 8,4 Hz, 1H), 6,52 (d, J = 12,0 Hz, 1H), 4,69 (s, 2H), 3,50 (s, 2H), 2,65 (m, 1H), 2,00-1,58 (m, 6H). 372,1 11/100 -
- 2
-
imagen21 1H-RMN (CD3OD/400 MHz): 7,31 (m, 1H), 7,00 (m, 3H), 4,80 (m, 2H), 3,56 (m, 2H), 2,66 (m, 1H), 2,00-1,59 (m, 6H). 410,1 3.788/39 -
- 3
-
imagen22 1H-RMN (CD3OD/400 MHz): 7,08 (m, 1H), 6,54 (m, 2H), 5,70 (m, 1H), 4,63 (m, 2H), 3,64 (m, 1H), 3,56 (m, 1H), 2,64 (m, 1H), 2,01-1,58 (m, 6H). 319,0 43.850/45 -
- 4
-
imagen23 1H-RMN (CD3OD/400 MHz): 7,34 (m, 5H), 6,60 (s, 1H), 5,60 (m, 1H), 4,80 (m, 1H), 3,40 (m, 2H), 2,40 (m, 1H), 2,01-1,58 (m, 6H). 361,9 1.482 /52 -
- 5
-
imagen24 1H-RMN (CD3OD/400 MHz): 7,40 (m, 5H), 6,80 (s, 1H), 5,48 (m, 2H), 3,50 (m, 2H), 2,34 (m, 1H), 2,01-1,58 (m, 6H). 352,0 4651/106 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 6
-
imagen25 1H-RMN (CDCl3/400 MHz; Se observaron rotámeros estables de amidas por RMN): 7,35 (m, 1H), 7,24 (br, 1H), 7,10 (m, 1H), 6,97 (m, 0,5H), 6,84 (m, 1H), 6,60 (m, 0,5H), 6,50 (m, 0,5H), 6,39 (m, 0,5H), 5,05 (s, 2H), 3,60 (s, 1H), 3,34 (s, 1H), 2,74 (m, 1H), 2,50-1,55 (m, 6H). 377,0 213/100 -
- 7
-
imagen26 1H-RMN (CD3OD/400 MHz): 7,31 (m, 1H), 7,04 (m, 3H), 5,04 (m, 1H), 5,04 (m, 1H), 3,70 (m, 1H), 3,50 (m, 1H), 2,56 (m, 1H), 2,00-1,56 (m, 6H). 368,0 3.446/87 -
- 8
-
imagen27 1H-RMN (CD3OD/400 MHz): 7,05 (m, 2H), 6,54 (m, 2H), 4,68 (m, 2H), 3,67 (m, 1H), 3,46 (m, 1H), 2,67 (m, 1H), 2,01-1,62 (m, 6H). 328,9 NA -
- 9
-
imagen28 1H-RMN (CD3OD/400 MHz): 7,30 (m, 1H), 7,10 (m, 2H), 6,50 (m, 1H), 4,77 (m, 2H), 3,53 (m, 2H), 2,66 (m, 1H), 2,00-1,59 (m, 6H). 377,0 15.400/80 -
- 10
-
imagen29 1H-RMN (CD3OD/400 MHz): 7,30 (m, 1H), 7,06 (m, 2H), 6,50 (m, 1H), 4,77 (m, 2H), 3,53 (m, 2H), 2,66 (m, 1H), 2,00-1,59 (m, 6H). 420,9 2.740/127 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 11
-
imagen30 1H-RMN (CD3OD/400 MHz): 7,06 (m, 1H), 6,60 (m, 3H), 4,80 (m, 2H), 4,00 (m, 4H), 3,75 (m, 2H), 3,10 (m, 1H). 382,9 10.400/61 -
- 12
-
imagen31 1H-RMN (CD3OD/400 MHz): 7,38 (m, 1H), 7,29 (m, 1H), 7,12 (m, 1H), 6,90 (m, 1H), 6,67 (m, 1H), 6,40 (m, 1H), 5,07 (m, 2H), 4,57 (m, 2H), 4,37 (m, 2H), 4,08 (m, 1H), 3,86 (m, 2H). 378,9 3.271/101 -
- 13
-
imagen32 1H-RMN (CD3OD/400 MHz): 7,33 (m, 1H), 7,27 (m, 1H), 7,07 (m, 1H), 6,73 (m, 2H), 6,36 (m, 1H), 6,40 (m, 1H), 5 ,17 (m, 2H), 3,42 (m, 2H), 1,02 (s, 9H). 379,0 49.110/33 -
- 14
-
imagen33 1H-RMN (CD3OD/400 MHz): 7,37 (m, 2H), 6,95 (m, 1H), 6,55 (m, 1H), 4,60 (m, 2H), 3,80 (m, 2H), 3,60 (m, 2H), 3,30 (m, 2H), 2,70 (m, 1H), 2,03-1,50 (m, 6H). 379,0 1.700/81 -
- 15
-
imagen34 1H-RMN (CD3OD/400 MHz): 7,01 (m, 1H), 6,82 (m, 1H), 6,60 (m, 1H), 6,54 (m, 1H), 4,88 (m, 2H), 4,67 (m, 4H), 4,44 (m, 2H), 3,78 (m, 1H). 373,9 150/102 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 16
-
imagen35 1H-RMN (CD3OD/400 MHz): 7,32 (m, 5H), 6,80 (m, 1H), 4,78 (m, 2H), 3,77 (m, 1H), 1,29 (m, 4H), 1,20 (m, 3H), 0,89 (m, 3H). 340,0 74.820/22 -
- 17
-
imagen36 1H-RMN (CD3OD/400 MHz): 7,25 (m, 4H), 6,83 (m, 1H), 4,80 (m, 2H), 3,40 (m, 2H), 1,62 (m, 2H), 1,29 (m, 4H), 0,87 (m, 3H). 350,7 138/83 -
- 18
-
imagen37 1H-RMN (CD3OD/400 MHz): 8,19 (m, 1H), 6,80 (m, 1H), 6,55 (m, 1H), 4,70 (m, 2H), 4,30 (m, 4H), 3,87 (m, 1H), 3,34 (m, 2H). 356,9 NA -
- 19
-
imagen38 1H-RMN (CD3OD/400 MHz): 7,34 (m, 5H), 6,80 (m, 1H), 4,77 (m, 2H), 3,47 (m, 2H), 1,62 (m, 2H), 1,23 (m, 4H), 0,89 (m, 3H). 340,0 920/76 -
- 20
-
imagen39 1H-RMN (CD3OD/400 MHz): 7,31 (m, 1H), 7,12 (m, 4H), 4,88 (m, 2H), 4,67 (m, 4H), 4,40 (m, 2H), 3,83 (m, 1H). 358,1 12.000/70 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 21
-
imagen40 1H-RMN (CD3OD/400 MHz): 7,28 (m, 1H), 7,14 (m, 2H), 6,56 (m, 1H), 3,93 (m, 3H), 3,80 (m, 2H), 3,40 (m, 2H), 2,77 (m, 1H), 1,89 (m, 2H), 1,44 (m, 2H). 388,5 >10.000 -
- 22
-
imagen41 1H-RMN (CD3OD/400 MHz): 7,38 (m, 2H), 7,14 (m, 3H), 3,95 (m, 2H), 3,40 (m, 2H), 3,40 (m, 3H), 1,95 (m, 2H), 1,86 (m, 2H), 1,10 (m, 2H). 388,5 1.516/99 -
- 23
-
imagen42 1H-RMN (CD3OD/400 MHz): 7,35 (m, 2H), 7,15 (m, 2H), 7,15 (m, 2H), 6,86 (m, 1H), 4,89 (s, 2H), 3,65 (m, 2H), 3,36 (m, 2H), 3,26 (m, 2H), 1,89 (m, 3H) 360,4 7.540/75 -
- 24
-
imagen43 1H-RMN (CD3OD/400 MHz): 7,11 (m, 2H), 6,55 (m, 2H), 4,76 (m, 2H), 3,67 (m, 4H), 3,31 (m, 2H), 1,16 (m, 3H). 376,4 210/100 -
- 25
-
imagen44 1H-RMN (CD3OD/400 MHz): 7,84 (m, 1H), 7,47 (m, 1H), 7,34 (m, 1H), 7,21 (m, 1H), 7,13 (m, 2H), 7,02 (m, 2H), 4,78 (m, 2H). 355,4 53.000/35 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 26
-
imagen45 1H-RMN (CD3OD/400 MHz): 7,40 (m, 2H), 7,15 (m, 2H), 7,84 (m, 1H), 4,90 (m, 2H), 3,78 (m, 4H), 3,32 (m, 2H), 2,07 (m, 2H), 1,69 (m, 2H), 1,50 (m, 1H). 386,4 377/99 -
- 27
-
imagen46 1H-RMN (DMSO-d6/400 MHz): 7,50 (m, 1H), 7,34 (m, 3H), 7,21 (m, 1H), 4,75 (m, 2H), 4,55 (m, 2H), 3,50 (m, 4H), 3,20 (m, 1H). 374,4 33.000/47 -
- 28
-
imagen47 1H-RMN (DMSO-d6/400 MHz): 7,92 (m, 1H), 7,72 (m, 2H), 7,60 (m, 1H), 7,51 (m, 2H), 5,00 (m, 2H), 4,65 (m, 2H), 4,40 (m, 4H), 3,20 (m, 1H). 365,4 NA -
- 29
-
imagen48 1H-RMN (CD3OD/400 MHz): 7,45 (m, 1H), 7,20 (m, 4H), 5,00 (m, 2H), 3,60 (m, 4H), 3,32 (m, 2H), 1,15 (m, 3H). 376,4 4.640/87 -
- 30
-
imagen49 1H-RMN (CD3OD/400 MHz): 7,38 (m, 2H), 7,13 (m, 3H), 4,85 (m, 2H), 3,76 (m, 2H), 3,47 (s, 2H), 3,43 (m, 2H), 1,49 (m, 3H). 360,4 9.770/72 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 31
-
imagen50 1H-RMN (CD3OD/400 MHz): 7,43 (m, 1H), 7,29 (m, 4H), 4,91 (m, 2H), 3,70 (m, 2H), 3,54 (m, 2H), 3,44 (m, 2H), 3,37 (m, 2H), 3,32 (s, 3H). 376,4 9.590/82 -
- 32
-
imagen51 1H-RMN (CD3OD/400 MHz): 7,03 (m, 4H), 6,50 (m, 1H), 4,63 (m, 2H), 3,57 (m, 2H), 3,10 (m, 2H), 3,02 (m, 2H), 1,30 (m, 4H), 1,15 (m, 3H). 416,4 1.002/107 -
- 33
-
imagen52 1H-RMN (CD3OD/400 MHz): 7,45 (m, 2H), 7,35 (m, 1H), 6,95 (m, 1H), 5,19 (m, 2H), 3,69 (m, 4H), 3,20 (m, 2H), 1,87 (m, 2H), 1,60 (m, 3H). 436,4 4.026/81 -
- 34
-
imagen53 1H-RMN (CD3OD/400 MHz): 7,15 (m, 1H), 7,02 (m, 1H), 6,58 (m, 1H), 6,52 (m, 1H), 4,74 (m, 2H), 3,77 (m, 4H), 3,44 (m, 2H), 2,14 (m, 2H), 1,64 (m, 3H). 402,4 77/109 -
- 35
-
imagen54 1H-RMN (CD3OD/400 MHz): 7,44 (m, 1H), 7,31 (m, 4H), 4,90 (m, 2H), 3,92 (m, 2H), 3,50 (m, 3H), 1,85 (m, 2H), 1,75 (m, 2H). 388,4 5.080/59 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 36
-
imagen55 1H-RMN (CD3OD/400 MHz): 7,44 (m, 1H), 7,32 (m, 3H), 6,80 (m, 1H), 4,91 (m, 2H), 3,68 (m, 2H), 3,47 (m, 2H), 3,11 (m, 2H), 1,45 (m, 7H). 416,4 1.218/88 -
- 37
-
imagen56 1H-RMN (DMSO-d6/400 MHz): 8,27 (m, 1H), 8,13 (m, 4H), 5,62 (m, 2H), 4,16 (m, 2H), 4,32 (m, 2H), 4,25 (m, 1H), 1,82 (d, 6H). 390,3 42.000/37 -
- 38
-
imagen57 1H-RMN (CD3OD/400 MHz): 7,42 (m, 1H), 7,29 (m, 4H), 4,89 (m, 2H), 3,50 (m, 2H), 3,41 (m, 4H), 1,92 (m, 2H), 1,12 (t, 6H). 300,3 33.000/47 -
- 39
-
imagen58 1H-RMN (CD3OD/400 MHz): 7,32 (m, 2H), 7,15 (m, 3H), 4,81 (m, 2H), 3,80 (m, 3H), 3,41 (m, 4H), 1,60 (m, 8H). 400,5 47.000/30 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 40
-
imagen59 1H-RMN (CD3OD/400 MHz): 7,41 (m, 1H), 7,00 (m, 3H), 4,88 (m, 2H), 3,70 (m, 4H), 3,40 (m, 2H), 2,05 (m, 2H), 1,62 (m, 2H), 1,40 (m, 1H). 404,4 1.171/114 -
- 41
-
imagen60 1H-RMN (CD3CN/400 MHz): 7,35 (m, 2H), 7,17 (m, 2H), 6,90 (m, 1H), 4,80 (d, 2H), 3,82 (m, 2H), 3,53 (m, 2H), 3,26 (m, 2H), 1,53(m, 5H), 1,16 (m, 2H). 400,4 1.258/118 -
- 42
-
imagen61 1H-RMN (CD3OD/400 MHz): 7,44 (d, 2H), 7,34 (t, 1H), 7,01 (m, 1H), 5,16 (m, 2H), 3,60 (m, 2H), 3,40 (m, 4H), 1,10 (m, 3H). 410,4 8.760/76 -
- 43
-
imagen62 1H-RMN (CD3OD/400 MHz): 7,46 (m, 1H), 7,20 (m, 3H), 6,88 (m, 1H), 4,85 (m, 2H), 3,80 (m, 2H), 3,60 (m, 1H), 3,48 (m, 2H), 3,25 (m, 1H), 2,01 (m, 2H), 1,70 (m, 2H), 1,45 (m, 1H). 402,4 1.330/110 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 44
-
imagen63 1H-RMN (CD3OD/400 MHz): 7,45 (m, 1H), 7,29 (m, 4H), 4,83 (m, 2H), 3,80 (m, 2H), 3,36 (m, 3H), 1,80 (m, 4H), 1,47 (m, 4H). 416,4 50.000/32 -
- 45
-
imagen64 1H-RMN (Acetona-d6/400 MHz): 7,40 (m, 2H), 7,28 (m, 3H), 4,98 (d, 2H), 3,84 (m, 2H), 3,61 (m, 1H), 3,40 (m, 1H), 3,28 (m, 2H), 2,08 (m, 1H), 1,63 (m, 2H), 1,30 (m, 2H). 386,4 25.150/52 -
- 46
-
imagen65 1H-RMN (CD3CN/400 MHz): 7,28 (m, 2H), 7,16 (m, 3H), 4,80 (d, 2H), 3,80 (m, 2H), 3,60 (m, 3H), 1,95 (m, 1H), 1,80 (m, 4H), 1,41 (m, 1H). 386,4 13.410/70 -
- 47
-
imagen66 1H-RMN (CD3OD/400 MHz): 7,33 (m, 2H), 7,12 (m, 2H), 6,90 (m, 1H), 4,81 (m, 2H), 4,20 (m, 1H), 3,14 (m, 1H), 2,09 (m, 2H), 1,82 (m, 2H), 1,66 (m, 2H), 1,21 (m, 2H). 400,4 435/89 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 48
-
imagen67 1H-RMN (CD3OD/400 MHz): 7,33 (m, 1H), 7,00 (m, 4H), 4,80 (m, 2H), 4,20 (m, 1H), 3,28 (s, 3H), 3,12 (m, 1H), 2,07 (m, 2H), 1,80 (m, 2H), 1,70 (m, 2H), 1,23 (m, 2H). 400,4 8.580/80 -
- 49
-
imagen68 1H-RMN (Acetona-d6/400 MHz): 7,40 (m, 1H), 7,00 (m, 3H), 4,92 (m, 2H), 3,24 (s, 3H), 3,00 (m, 2H), 1,76 (m, 4H), 1,15 (m, 4H). 418,4 914/122 -
- 50
-
imagen69 1H-RMN (Acetona-d6/400 MHz): 7,17 (m, 2H), 7,07 (m, 2H), 4,90 (m, 2H), 4,15 (m, 1H), 3,24 (s, 3H), 3,05 (m, 3H), 1,96 (m, 2H), 1,80 (m, 2H), 1,24 (m, 2H). 418,4 1.667/90 -
- 51
-
imagen70 1H-RMN (Acetona-d6/400 MHz): 7,03 (m, 3H), 6,89 (m, 1H), 4,80 (m, 2H), 4,32 (m, 1H), 3,25 (s, 3H), 3,05 (m, 3H), 1,96 (m, 2H), 1,80 (m, 2H), 1,20 (m, 2H). 418,4 50.380/31 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 52
-
imagen71 1H-RMN (CD3OD/400 MHz): 7,40 (m, 1H), 7,30 (m, 4H), 4,81 (m, 2H), 3,29 (s, 3H), 3,13 (m, 2H), 2,10 (m, 2H), 1,85 (m, 2H), 1,62 (m, 2H), 1,23 (m, 2H). 416,4 879/100 -
- 53
-
imagen72 1H-RMN (CD3OD/400 MHz): 7,40 (m, 1H), 7,30 (m, 4H), 4,79 (m, 2H), 3,79 (m, 2H), 2,00 (m, 2H), 1,85 (m, 2H), 1,63 (m, 2H), 1,22 (m, 2H), 1,10 (d, 6H). 444,4 2.287/63 -
- 54
-
imagen73 1H-RMN (CD3OD/400 MHz): 7,45 (m, 1H), 7,27 (m, 3H), 6,80 (m, 1H), 4,80 (m, 2H), 4,22 (m, 1H), 3,25 (s, 3H), 3,05 (m, 1H), 2,05 (m, 2H), 1,84 (m, 2H), 1,66 (m, 2H), 1,20 (m, 2H). 397,5 365/93 -
- 55
-
imagen74 1H-RMN (CD3OD/400 MHz): 7,30 (m, 2H), 7,08 (m, 3H), 4,78 (m, 2H), 4,20 (m, 1H), 3,50 (m, 2H), 3,20 (m, 1H), 2,05 (m, 2H), 1,80 (m, 2H), 1,70 (m, 2H), 1,20 (m, 2H), 1,12 (t, 3H). 414,4 469/101 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 56
-
imagen75 1H-RMN (Acetona-d6/400 MHz): 8,53 (m, 1H), 7,86 (m, 1H), 7,37 (m, 1H), 6,63 (m, 1H), 5,00 (m, 2H), 4,20 (m, 1H), 3,25 (s, 3H), 3,08 (m, 1H), 1,95 (m, 4H), 1,42 (m, 2H), 1,26 (m, 2H). 417,4 2.580/48 TFA
- 57
-
imagen76 1H-RMN (dmso-d6/400 MHz): 7,06 (m, 1H), 6,54 (m, 2H), 6,30 (m, 1H), 4,54 (m, 2H), 4,10 (m, 1H), 3,20 (s, 3H), 3,00 (m, 1H), 1,95 (m, 2H), 1,70 (m, 2H), 1,50 (m, 4H), 1,15 (m, 2H). 431,4 TBD TFA
- 58
-
imagen77 1H-RMN (CD3OD/400 MHz): 7,10 (m, 1H), 6,89 (m, 1H), 6,71 (m, 1H), 6,38 (m, 1H), 4,75 (m, 2H), 4,31 (m, 1H), 3,20 (s, 3H), 3,10 (m, 1H), 2,10 (m, 2H), 1,90 (m, 2H), 1,65 (m, 2H), 1,28 (m, 2H). 431,4 TBD TFA
- 59
-
imagen78 1H-RMN (CD3CN/400 MHz): 7,35 (m, 2H), 7,16 (m, 2H), 6,80 (m, 1H), 4,77 (m, 2H), 3,85 (m, 4H), 3,52 (m, 2H), 2,30 (m, 2H), 1,62 (m, 5H), 1,17 (m, 4H). 465,5 494/100 -
- 60
-
imagen79 1H-RMN (CDCl3/400 MHz): 7,35 (m, 1H), 7,18 (m, 3H), 6,70 (m, 1H), 4,87 (m, 2H), 3,59 (m, 2H), 2,28 (m, 4H), 2,04 (m, 2H), 1,70 (m, 3H), 1,44 (m, 2H). 412,5 101/105 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 61
-
imagen80 1H-RMN (DMSO-d6/400 MHz): 7,32 (m, 1H), 7,20 (m, 4H), 4,73 (m, 2H), 3,30 (m, 2H), 3,13 (m, 2H), 2,93 (s, 3H), 1,99 (m, 2H). 408,4 NA -
- 62
-
imagen81 1H-RMN (DMSO-d6/400 MHz): 7,46 (m, 1H), 7,35 (m, 3H), 6,85 (m, 1H), 4,91 (m, 2H), 3,60 (m, 2H), 3,10 (m, 2H), 2,72 (m, 1H), 2,41 (m, 2H), 1,85 (m, 2H). 450,4 273/105 -
- 63
-
imagen82 1H-RMN (CD3OD/400 MHz): 7,36 (m, 2H), 7,15 (m, 2H), 6,85 (m, 1H), 4,92 (m, 2H), 3,50 (m, 2H), 3,12 (m, 2H), 3,00 (m, 1H), 2,71 (m, 2H), 2,24 (m, 2H), 1,85 (m, 2H). 434,4 240/87 -
- 64
-
imagen83 1H-RMN (DMSO-d6/400 MHz): 7,52 (m, 2H), 7,35 (m, 1H), 7,38 (m, 1H), 5,03 (m, 2H), 3,50 (m, 2H), 3,12 (m, 2H), 2,92 (m, 3H), 2,16 (m, 2H), 1,65 (m, 2H). 484,3 3.780/71 -
- 65
-
imagen84 1H-RMN (CD3OD/400 MHz): 7,47 (m, 1H), 7,37 (m, 3H), 6,80 (m, 1H), 4,97 (m, 2H), 3,90 (m, 2H), 3,42 (m, 2H), 3,12 (m, 2H), 1,33 (m, 3H). 424,3 NA -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 66
-
imagen85 1H-RMN (CD3OD/400 MHz): 7,41 (m, 1H), 7,00 (m, 3H), 5,01 (m, 2H), 3,58 (m, 2H), 3,10 (m, 2H), 2,65 (m, 1H), 2,35 (m, 2H), 1,77 (m, 4H). 452,4 375/102 -
- 67
-
imagen86 1H-RMN (CD3OD/400 MHz): 7,39 (m, 1H), 7,02 (m, 3H), 6,90 (m, 1H), 4,80 (m, 2H), 3,60 (m, 3H), 3,20 (m, 3H), 2,99 (m, 2H), 2,30 (m, 3H). 434,4 1.626/95 -
- 68
-
imagen87 1H-RMN (Acetona-d6/400 MHz): 7,20 (m, 4H), 4,98 (d, 2H), 3,61 (m, 2H), 3,20 (m, 2H), 3,00 (m, 2H), 2,60 (m, 1H), 2,45 (m, 2H), 1,80 (m, 2H). 452,4 766/103 -
- 69
-
imagen88 1H-RMN (Acetona-d6/400 MHz): 7,00 (m, 4H), 4,90 (d, 2H), 3,61 (m, 2H), 3,20 (m, 2H), 3,00 (m, 2H), 2,60 (m, 1H), 2,45 (m, 2H), 1,80 (m, 2H). 452,4 1.835/74 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 70
-
imagen89 1H-RMN (Acetona-d6/400 MHz): 7,20 (m, 4H), 4,90 (d, 2H), 3,61 (m, 2H), 3,20 (m, 2H), 3,00 (m, 2H), 2,60 (m, 1H), 2,45 (m, 2H), 1,80 (m, 2H). 452,4 884/91 -
- 71
-
imagen90 1H-RMN (Acetone-d6/400 MHz): 7,30 (m, 2H), 7,18 (m, 2H), 7,00 (m, 1H), 4,90 (d, 2H), 3,61 (m, 2H), 3,00 (m, 4H), 2,25 (m, 1H), 2,15 (m, 2H), 1,87 (m, 2H). 434,4 10.200/71 -
- 72
-
imagen91 1H-RMN (Acetona-d6/400 MHz): 7,36 (m, 4H), 7,00 (m, 1H), 4,95 (d, 2H), 3,61 (m, 2H), 3,00 (m, 4H), 2,25 (m, 1H), 2,15 (m, 2H), 1,87 (m, 2H). 450,4 19.660/22 -
- 73
-
imagen92 1H-RMN (Acetona-d6/400 MHz): 7,41 (m, 4H), 6,80 (m, 1H), 4,95 (d, 2H), 3,61 (d, 2H), 2,60 (m, 4H), 1,99 (m, 1H), 1,61 (m, 2H), 1,30 (m, 4H). 432,4 1.343/79 -
- 74
-
imagen93 1H-RMN (Acetona-d6/400 MHz): 7,41 (m, 4H), 6,90 (m, 1H), 4,95 (d, 2H), 3,61 (d, 2H), 3,16 (m, 2H), 2,81 (m, 1H), 2,53 (m, 2H), 2,08 (m, 2H), 1,73 (m, 4H). 448,4 640/95 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 75
-
imagen94 1H-RMN (CD3CN/400 MHz): 7,47 (m, 1H), 7,32 (m, 3H), 6,90 (m, 1H), 4,85 (m, 2H), 3,49 (m, 2H), 2,90 (m, 4H), 2,25 (m, 2H), 2,05 (m, 1H), 1,61 (m, 4H). 464,4 188/102 -
- 76
-
imagen95 1H-RMN (CD3CN/400 MHz): 7,15 (m, 1H), 6,80 (m, 1H), 6,60 (m, 2H), 4,72 (m, 2H), 3,50 (m, 2H), 3,19 (m, 2H), 2,95 (m, 1H), 2,55 (m, 1H), 2,35 (m, 2H), 1,80 (m, 3H). 450,4 54/93 -
- 77
-
imagen96 1H-RMN (CD3CN/400 MHz): 7,40 (m, 1H), 7,15 (m, 2H), 6,95 (m, 1H), 6,75 (m, 2H), 5,65 (s, 1H), 5,38 (s, 1H), 3,48 (m, 2H), 3,40 (m, 1H), 3,05 (m, 1H), 3,00 (m, 1H), 2,45 (m, 2H), 1,75 (m, 4H). 431,4 34.820/43 -
- 78
-
imagen97 1H-RMN (CD3CN/400 MHz): 7,47 (m, 2H), 7,18 (m, 2H), 6,90 (m, 1H), 4,85 (d, 2H), 3,59 (d, 2H), 2,90 (m, 4H), 2,05 (m, 1H), 2,70 (m, 6H). 448,4 485/102 -
- 79
-
imagen98 1H-RMN (Acetona-d6/400 MHz): 7,21 (m, 5H), 4,70 (d, 2H), 3,40 (d, 2H), 2,47 (m, 2H), 1,86 (m, 1H), 1,70 (m, 2H), 1,41 (m, 2H), 1,14 (m, 4H). 416,4 1.193/95 -
- 80
-
imagen99 1H-RMN (Acetonad6/400MHz): 7,35 (m, 1H), 7,18 (m, 2H), 4,70 (d, 2H), 3,60 (d, 2H), 2,60 (m, 2H), 2,50 (m, 2H), 2,00 (m, 2H), 1,61 (m, 2H), 1,27 (m, 3H). 382,4 1.301/46 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 81
-
imagen100 1H-RMN (CD3CN/400 MHz): 7,36 (m, 2H), 7,17 (m, 2H), 6,60 (m, 1H), 4,90 (d, 2H), 3,63 (d, 2H), 3,01 (m, 4H), 2,18 (m, 3H), 1,70 (m, 4H). 414,4 1.366/72 -
- 82
-
imagen101 1H-RMN (Acetona-d6/400 MHz): 7,35 (m, 2H), 7,15 (m, 2H), 6,55 (m, 1H), 4,90 (d, 2H), 3,60 (d, 2H), 2,60 (m, 4H), 2,00 (m, 2H), 1,60 (m, 2H), 1,25 (m, 3H). 426,4 1.372/74 -
- 83
-
imagen102 1H-RMN (CD3CN/400 MHz): 7,36 (m, 2H), 7,18 (m, 2H), 6,60 (m, 1H), 4,90 (d, 2H), 3,60 (d, 2H), 2,98 (m, 4H), 2,19 (m, 2H), 1,71 (m, 5H). 458,4 1.104/98 -
- 84
-
imagen103 1H-RMN (ACN-d3/400 MHz): 7,40 (m, 1H), 7,02 (m, 2H), 6,98 (m, 1H), 4,83 (m, 2H), 3,35 (m, 2H), 2,51 (m, 4H), 2,17 (m, 2H), 1,90 (m, 2H), 1,48 (m, 2H), 1,21 (m, 3H). 434,4 697/73 -
- 85
-
imagen104 1H-RMN (CD3CN/400 MHz): 7,36 (m, 2H), 7,05 (m, 3H), 5,00 (m, 2H), 3,60 (m, 2H), 2,99 (m, 4H), 2,90 (m, 2H), 1,68 (m, 5H), 2,98 (m, 4H). 466,4 64/100 -
- 86
-
imagen105 1H-RMN (Acetona-d6/400 MHz): 7,22 (m, 1H), 7,00 (m, 1H), 6,63 (m, 2H), 4,75 (m, 2H), 3,40 (m, 2H), 2,60 (m, 4H), 2,00 (m, 2H), 1,55 (m, 2H), 1,25 (m, 3H). 432,4 93/98 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 87
-
imagen106 1H-RMN (CD3CN/400 MHz): 7,15 (m, 1H), 6,84 (m, 1H), 6,63 (m, 2H), 4,72 (m, 2H), 3,44 (m, 2H), 2,92 (m, 4H), 2,04 (m, 2H), 1,60 (m, 5H). 464,4 64/100 -
- 88
-
imagen107 1H-RMN (CD3OD/400 MHz): 8,77 (m, 1H), 7,98 (m, 1H), 7,60 (m, 2H), 6,97 (m, 1H), 5,00 (m, 2H), 3,60 (m, 2H), 3,20 (m, 2H), 2,40 (m, 2H), 1,84 (m, 3H). 417,4 3.600/96 -
- 89
-
imagen108 1H-RMN (CD3OD/400 MHz): 8,80 (m, 1H), 7,90 (m, 3H), 6,97 (m, 1H), 5,10 (m, 2H), 3,85 (m, 2H), 3,20 (m, 2H), 2,80 (m, 2H), 2,40 (m, 2H), 1,90 (m, 3H). 417,4 58.000/35 TFA
- 90
-
imagen109 1H-RMN (CD3OD/400 MHz): 8,70 (m, 2H), 8,27 (m, 1H), 7,91 (m, 1H), 4,84 (m, 2H), 3,64 (m, 2H), 3,10 (m, 2H), 2,65 (m, 1H), 2,30 (m, 2H), 1,80 (m, 4H). 417,4 52.000/24 TFA
- 91
-
imagen110 1H-RMN (CD3OD/400 MHz): 7,09 (m, 1H), 6,90 (m, 1H), 6,52 (m, 1H), 6,41 (m, 1H), 4,84 (m, 2H), 3,50 (m, 4H), 2,80 (m, 5H), 1,55 (m, 4H). 463,4 58/78 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 92
-
imagen111 1H-RMN (Acetona-d6/400 MHz): 8,50 (m, 1H), 7,92 (m, 1H), 7,42 (m, 2H), 6,76 (m, 1H), 5,11 (m, 2H), 3,64 (m, 2H), 3,10 (m, 2H), 2,65 (m, 1H), 2,30 (m, 2H), 1,80 (m, 4H). 451,4 1.290/74 TFA
- 93
-
imagen112 1H-RMN (Acetona-d6/400 MHz): 8,94 (m, 1H), 7,90 (m, 1H), 7,05 (m, 1H), 5,10 (m, 2H), 3,75 (m, 2H), 3,20 (m, 2H), 2,90 (m, 1H), 2,70 (m, 1H), 2,40 (m, 2H), 1,80 (m, 3H). 423,6 49.000/26 -
- 94
-
imagen113 1H-RMN (CDCl3/400 MHz): 7,83 (m, 1H), 7,46 (m, 2H), 6,50 (m, 1H), 5,10 (m, 2H), 3,60 (m, 2H), 3,20 (m, 2H), 3,00 (m, 1H), 2,90 (m, 1H), 2,70 (m, 1H), 2,40 (m, 2H), 1,88 (m, 3H). 495,4 2.380/69 -
- 95
-
imagen114 1H-RMN (CD3CN/400 MHz): 7,17 (m, 1H), 6,64 (m, 2H), 6,52 (m, 1H), 4,62 (m, 2H), 3,49 (m, 1H), 3,30 (m, 1H), 3,10 (m, 2H), 2,90 (m, 1H), 2,70 (m, 1H), 2,20 (m, 2H), 1,73 (m, 3H). 465,4 TBD TFA
- 96
-
imagen115 1H-RMN (CD3CN/400 MHz): 7,06 (m, 1H), 6,80 (m, 1H), 6,56 (m, 1H), 6,47 (m, 1H), 4,77 (m, 2H), 3,50 (m, 2H), 3,10 (m, 2H), 2,90 (m, 1H), 2,80 (m, 1H), 2,60 (m, 1H), 2,30 (m, 2H), 1,80 (m, 3H). 465,4 TDB TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 1H-RMN (CD3CN/400 MHz):
- 7,96 (m, 1H), 7,60 (m, 2H), 7,10
- 97
- (m, 1H), 5,34 (m, 2H), 4,10 (m, 479,4 TDB TFA
- 2H), 3,59 (m, 4H), 2,50 (m, 2H),
- 2,17 (m, 5H).
- 1H-RMN (Acetona-d6/400
- MHz): 7,37 (m, 2H), 7,13 (m,
- 98
- 2H), 7,00 (m, 1H), 5,00 (m, 2H), 399,4 2.050/56 TFA
- 3,62 (m, 4H), 3,00 (m, 2H), 1,55
- (m, 7H).
- 1H-RMN (CDCl3/400 MHz):
- 7,35 (m, 2H), 7,16 (m, 2H), 6,66
- 99
- (m, 1H), 4,87 (m, 2H), 3,77 (m, 2H), 3,53 (m, 2H), 2,74 (s, 3H), 477,5 110/100 -
- 2,61 (m, 2H), 1,60 (m, 4H), 1,36
- (m, 3H).
- 1H-RMN (DMSO-d6/400 MHz):
- 9,32 (m, 1H), 7,43 (m, 1H), 7,20
- 100
- (m, 3H), 6,94 (m, 1H), 4,80 (m, 399,5 101.000/29 TFA
- 2H), 3,40 (m, 4H), 2,90 (m, 5H),
- 1,90 (m, 3H), 1,40 (m, 2H).
- 1H-RMN (DMSO-d6/400 MHz):
- 7,92 (m, 1H), 7,72 (m, 2H), 7,60
- 101
- (m, 1H), 7,51 (m, 2H), 5,00 (m, 365,4 1.856/96 TFA
- 2H), 4,65 (m, 2H), 4,40 (m, 4H),
- 3,20 (m, 1H).
- 102
-
imagen116 1H-RMN (CD3OD/400 MHz): 7,45 (m, 1H), 7,32 (m, 4H), 5,05 (m, 2H), 3,80 (m, 2H), 2,95 (m, 4H), 2,55 (m, 5H), 1,62 (m, 5H). 441,5 767/71 TFA
- 1H-RMN (CD3OD/400 MHz):
- 7,34 (m, 2H), 7,14 (m, 2H), 6,80
- 103
- (m, 1H), 4,94 (m, 2H), 3,74 (m, 2H), 3,31 (m, 4H), 3,12 (m, 4H), 414,5 37.000/42 2TF A
- 2,85 (m, 5H).
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 104
-
imagen117 1H-RMN (CD3OD/400 MHz): 7,45 (m, 1H), 7,32 (m, 3H), 6,80 (m, 1H), 5,00 (m, 2H), 3,76 (m, 4H), 3,38 (m, 4H), 2,96 (m, 2H), 2,88 (m, 5H). 430,3 17.000/63 2TF A
- 105
-
imagen118 1H-RMN (CD3OD/400 MHz): 7,46 (d, 2H), 7,36 (t, 1H), 7,05 (m, 1H), 5,22 (m, 2H), 3,50 (m, 2H), 3,35 (m, 2H), 3,11 (m, 2H), 2,81 (m, 2H), 1,95 (m, 2H), 1,45 (m, 4H), 1,30 (m, 6H). 477,4 3268/71 TFA
- 106
-
imagen119 1H-RMN (Acetona-d6/400 MHz): 7,37 (m, 2H), 7,16 (m, 3H), 5,00 (m, 2H), 3,90 (m, 2H), 3,60 (m, 6H), 3,25 (m, 6H), 1,34 (m, 3H). 428,5 6.300/115 2TF A
- 107
-
imagen120 1H-RMN (CD3OD/400 MHz): 7,45 (m, 1H), 7,34 (m, 3H), 6,80 (m, 1H), 5,01 (m, 2H), 3,78 (m, 2H), 3,47 (m, 2H), 3,28 (m, 2H), 3,04 (m, 2H), 2,91 (m, 4H). 465,4 873/65 TFA
- 108
-
imagen121 1H-RMN (CD3OD/400 MHz): 7,40 (m, 2H), 7,20 (m, 3H), 5,00 (m, 2H), 3,65 (m, 2H), 3,50 (m, 2H), 3,40 (m, 2H), 3,25 (m, 2H), 3,00 (m, 4H). 449,4 7.800/92 TFA
- 109
-
imagen122 1H-RMN (CD3OD/400 MHz): 7,40 (m, 1H), 7,10 (m, 3H), 5,05 (m, 2H), 3,65 (m, 2H), 3,45 (m, 2H), 3,25 (m, 2H), 3,00 (m, 6H). 467,4 4.200/94 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 110
-
imagen123 1H-RMN (Acetona-d6/400 MHz): 7,52 (m, 2H), 7,43 (m, 1H), 7,20 (m, 1H), 5,20 (m, 2H), 3,60 (m, 2H), 3,00 (m, 10H). 499,3 1.644/84 TFA
- 111
-
imagen124 1H-RMN (Acetona-d6/400 MHz): 7,28 (m, 4H), 5,08 (m, 2H), 3,91 (m, 2H), 3,60 (m, 2H), 3,16 (m, 8H). 467,4 13.100/64 TFA
- 112
-
imagen125 1H-RMN (Acetona-d6/400 MHz): 7,58 (m, 1H), 7,40 (m, 2H), 6,78 (m, 1H), 5,04 (m, 2H), 3,90 (m, 2H), 3,71 (m, 2H), 3,47 (m, 4H), 3,14 (m, 4H). 446,4 1.066/91 2TF A
- 113
-
imagen126 1H-RMN (CD3OD/400 MHz): δ 7,30 (m, 1H), 7,02 (m, 2H), 6,95 (m, 1H), 4,78 (m, 2H), 3,57 (m, 2H), 2,65 (m, 1H), 2,02 (m, 2H), 1,78 (m, 4H). 418,0 77.000/21 -
- 114
-
imagen127 1H-RMN (CD3OD/400 MHz): δ 7,20 (m, 1H), 6,95 (m, 2H), 6,55 (m, 1H), 5,60 (d, 2H), 4,70 (m, 2H), 3,57 (m, 2H), 2,60 (m, 1H), 2,02-1,80 (m, 6H). 448,0 TBD -
- 115
-
imagen128 1H-RMN (CD3OD/400 MHz): δ 7,30 (m, 1H), 7,05 (m, 2H), 6,55 (m, 1H), 4,95 (d, 2H), 3,60 (m, 2H), 2,80 (m, 1H), 2,05 (m, 1H), 2,00 (m, 5H), 1,80 (m, 5H), 1,00 (t, 3H). 437,1 98/104 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 116
-
imagen129 1H-RMN (CD3OD/400 MHz): 8,50 (s, 1H), 8,38 (d, 1H), 7,43 (m, 1H), 6,55 (m, 1H), 4,88 (m, 2H), 3,60 (m, 2H), 2,66 (m, 1H), 2,10-1,20 (m, 6H). 323,4 38.000/NA TFA
- 117
-
imagen130 1H-RMN (CD3OD/400 MHz): 8,44 (d, 1H), 8,15 (d, 1H), 7,43 (m, 1H), 6,60 (m, 1H), 4,74 (m, 2H), 3,70 (m, 2H), 2,66 (m, 1H), 2,10-1,20 (m, 6H). 339,5 NA/NA TFA
- 118
-
imagen131 1H-RMN (CD3OD/400 MHz): 11,4(s, 1H), 7,57 (s, 1H), 7,43 (d, 1H), 7,21 (t, 1H), 6,60-7,13(m, 1H), 4,90 (m, 2H), 3,75 (m, 2H), 2,87 (s, 6H), 2,71 (m, 1H), 2,10-1,50 (m, 6H). 400,4 7.000/100 TFA
- 119
-
imagen132 1H-RMN (CD3OD/400 MHz): 8,20 (m, 1H), 7,55 (m, 1H), 7,26 (m, 1H), 7,10 (m, 1H), 6,32-6,58(m, 1H), 5,00 (s, 2H), 3,52 (m, 2H), 2,60 (m, 1H), 2,00-1,50 (m, 6H). 344,4 2.933/100 -
- 120
-
imagen133 1H-RMN (CD3OD/400 MHz): 8,20 (m, 1H), 7,56 (m, 1H), 7,28 (m, 1H), 7,11 (m, 1H), 6,43-6,67(m, 1H), 5,05 (s, 2H), 3,54 (m, 2H), 2,61 (m, 1H), 2,00-1,50 (m, 6H). 388,4/390,4 1.335/100 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 121
-
imagen134 1H-RMN (CD3OD/400 MHz): 11,2(s, 1H), 7,52 (nd, 1H), 7,41 (d, 1H), 7,21 (t, 1H), 6,60-7,13(m, 1H), 5,03 (bs, 2H), 3,80 (m, 2H), 2,73 (s, 6H), 2,71 (m, 1H), 2,10-1,50 (m, 6H). 23.000/NA TFA
- 122
-
imagen135 1H-RMN CD3OD/400 MHz): 7,96(m, 1H), 7,78 (m, 1H), 7,00 (m, 1H), 6,67-6,24 (m, 1H), 4,63 (m, 2H), 3,61 (m, 2H), 2,61 (m, 1H), 2,10-1,50 (m, 6H). NA/NA NA/NA -
- 123
-
imagen136 1H-RMN (CD3OD/400 MHz): 8,20 (m, 1H), 7,57 (m, 1H), 7,29 (m, 1H), 7,14 (m, 1H), 6,43-6,67(m, 1H), 5,03 (s, 2H), 3,54 (m, 2H), 2,61 (m, 1H), 2,00-1,50 (m, 6H). 828/100 -
- 124
-
imagen137 1H-RMN (CD3OD/400 MHz): 7,08 (m, 1H), 7,00 -6,60(m, 3H), 4,80 (m, 2H), 3,51 (m, 2H), 2,65 (m, 1H), 2,10-1,50 (m, 6H). 21/100 -
- 125
-
imagen138 1H-RMN (CD3OD/400 MHz): 7,08 (m, 1H), 6,83(m, 1H), 6,71(m, 1H), 6,63-6,36(m, 1H), 4,74 (m, 2H), 3,46 (m, 2H), 2,64 (m, 1H), 2,10-1,50 (m, 6H). 35/100 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 126
-
imagen139 1H-RMN (CD3OD/400 MHz): 9,00-8,40 (m, 1H), 7,75-7,35 (m, 2H), 6,98 (m, 1H), 5,18 (s, 2H), 3,56 (m, 2H), 2,65 (m, 1H), 2,10-1,50 (m, 6H). NA/NA -
- 127
-
imagen140 1H-RMN (CD3OD/400 MHz): 7,44 (m, 1H), 7,32 (m, 4H), 4,86 (m, 2H), 3,58 (m, 2H), 2,65 (m, 1H), 2,10-1,50 (m, 6H). 258/100 -
- 128
-
imagen141 1H-RMN (CD3OD/400 MHz): 8,56 (s, 1H), 8,45 (m, 1H), 7,32 (m, 1H), 7,04(m, 1H), 4,88 (m, 2H), 3,70 (m, 2H), 2,68 (m, 1H), 2,10-1,50 (m, 6H). 9.300/75 -
- 129
-
imagen142 1H-RMN (CD3OD/400 MHz): rotámeros 7,22+7,11 (t, 1H), 6,55(m, 2H), 6,31+6,27(s, 1H), 4,98+4,70 (s, 2H), 3,98+3,58 (m, 2H), 2,59+2,42 (m, 2H), 1,94(m, 1H), 0,99 (m, 2H), 0,73(m, 2H). 10.500/NA -
- 130
-
imagen143 1H-RMN (CD3OD/400 MHz): 7,08 (m, 2H), 6,61(d, 1H), 6,56(dd, 1H), 4,80 (m, 2H), 3,65 (m, 2H), 2,48 (m, 1H). 1000/100 -
- 131
-
imagen144 1H-RMN (CD3OD/400 MHz): 7,14 (m, 2H), 6,60(m, 1H), 6,54(d, 1H), 4,73 (m, 2H), 3,57 (m, 2H), 1,77 (m, 2H), 1,17(s, 3H), 1,13(s, 3H). 23.000/NA -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 132
-
imagen145 1H-RMN (CD3OD/400 MHz): 7,07 (t, 1H), 6,59(d, 1H), 6,52(dd, 1H), 4,67(s, 2H), 4,54 (m, 1H), 2,00-1,50 (m, 8H). 213/100 -
- 133
-
imagen146 1H-RMN (CD3OD/400 MHz): 7.08 (m, 1H), 6.84(m, 1H), 6.63(d, 1H), 6.58(dd, 1H), 4.82 (m, 2H), 3.73 (m, 2H), 3.11 (m, 2H). 1.270/100 TFA
- 134
-
imagen147 1H-RMN (CD3OD/400 MHz): 7.15-6.55(m, 4H), 4.73 (m, 2H), 3.51 (m, 2H), 2.65 (m, 1H), 2.10-1.50 (m, 6H). 1.075/100 -
- 135
-
imagen148 1H-RMN (d6DMSO/400 MHz): 11.2(s, 1H), 7.33 (m, 3H), 7.06 (t, 1H), 6.88 (d, 1H), 6.52(m, 1H), 6.42(s, 1H), 5.05 (s, 1H), 4.84(d, 1H), 3.54 (m, 1H), 1.94 (m, 2H), 1.68 (m, 2H), 1.53 (m, 2H). 68/100 TFA
- 136
-
imagen149 1H-RMN (CD3OD/400 MHz): 7,10-6,55(m, 4H), 4,79 (s, 1H), 3,98(s, 1H), 3,59 (m, 1H), 2,65 (m, 2H), 2,10-1,50 (m, 6H). 380/100 -
- 137
-
imagen150 1H-RMN (CD3OD/400 MHz): 7,30-6,75 (m, 2H), 6,60(d, 1H), 6,53(d, 1H), 4,77 (s, 2H), 3,74 (m, 2H), 3,59 (m, 2H). 6.200/70 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 138
-
imagen151 1H-RMN (CD3OD/400 MHz): 7,30-6,75 (m, 2H), 6,60(d, 1H), 6,53(d, 1H), 4,90 (m, 2H), 3,74 (m, 2H), 1,23 (m, 6H). NA/NA -
- 139
-
imagen152 1H-RMN (CD3OD/400 MHz): 7,11 (m, 1H), 6,86(m, 1H), 6,57(d, 1H), 6,51(d, 1H), 4,70(s, 2H), 4,10 (m, 1H), 1,77(m, 5H), 1,58(m, 4H), 1,44-1,04(m, 4H). 152/100 -
- 140
-
imagen153 1H-RMN (CD3OD/400 MHz): rotámeros 7,24+7,04 (t, 1H), 6,94+6,81(s, 1H), 6,60(d, 1H), 6,53(dd, 1H), 4,76+4,72 (s, 2H), 3,59+3,50 (m, 2H), 1,48(q, 2), 0,67+0,53 (m, 2H), 0,41(m, 2H), 0,01(m, 2H). 32/100 -
- 141
-
imagen154 1H-RMN (CD3OD/400 MHz): 8,20-6,60(m, 4H), 4,81-4,45 (m, 2H), 3,61(m, 1H), 3,22 (m, 1H), 2,65 (m, 1H), 2,10-1,50 (m, 6H). 6.500/100 -
- 142
-
imagen155 1H-RMN (CD3OD/400 MHz): 7,30-6,75 (m, 2H), 6,59(d, 1H), 6,53(dd, 1H), 4,76 (s, 2H), 3,63 (m, 4H), 3,31 (s, 3H). 1.190/100 -
- 143
-
imagen156 1H-RMN (CD3OD/400 MHz): 7,15(nt, 1H), 6,97 (s, 1H), 6,65(d, 1H), 6,59(dd, 1H), 4,91 (s, 2H), 3,80(m, 2H), 3,25 (m, 6H), 1,30 (t, 6H). 108/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 144
-
imagen157 1H-RMN (CD3OD/400 MHz): 9,38(s, 1H), 7,78(d, 1H), 7,67(s, 1H), 7,60(t, 1H), 7,51 (m, 1H), 7,08(s, 1H), 6,32(s, 1H), 5,06(s, 2H). 25.000/NA TFA
- 145
-
imagen158 1H-RMN (CD3OD/400 MHz): 7,50-6,95(m, 4H), 4,81(s, 2H), 4,26(s, 2H), 3,82(m, 2H), 2,72(m, 1H), 2,10-1,50(m, 6H). 25.500/NA TFA
- 146
-
imagen159 1H-RMN (CD3OD/400 MHz): 9,48(m, 1H), 7,63(t, 1H), 7,40-7,00(m, 3H), 6,62(m, 1H), 4,49(m, 2H), 4,26(m, 2H). 385,5 NA/NA TFA
- 147
-
imagen160 1H-RMN (CD3OD/400 MHz): 7,00(m, 1H), 6,27(m, 2H), 4,69(s, 2H), 4,48(s, 2H), 3,56(m, 2H), 2,68(m, 1H), 2,10-1,50(m, 6H). 358,4 NA/NA -
- 148
-
imagen161 1H-RMN (CD3OD/400 MHz): 7,36(m, 2H), 7,19(m, 2H), 6,87(s, 1H), 4,99(m, 2H), 3,86(m, 2H), 3,30 (m, 6H), 1,31 (t, 6H). 387,5 505/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 149
-
imagen162 1H-RMN (CD3OD/400 MHz): 7,46-7,06(m, 4H), 7,00-6,73(m, 1H), 4,90(m, 2H), 3,65(m, 2H), 1,51(q, 2H), 0,62(m, 1H), 0,42(m, 2H), 0,02 (m, 2H). 356,5 1.995/100 -
- 150
-
imagen163 1H-RMN (CD3OD/400 MHz): 7,46-6,70(m, 5H), 4,92(m, 2H), 3,96-3,42(m, 6H), 2,68(m, 1H), 2,02(m, 1H), 1,62(m, 1H). 372,4 16.000/68 -
- 151
-
imagen164 1H-RMN (CD3OD/400 MHz): 7,39-7,09(m, 5H), 4,87(m, 2H), 4,00(m, 1H), 3,80(m, 2H), 3,67(m, 1H), 3,29(m, 1H), 2,30(m, 1H), 2,06(m, 1H). 358,4 NA/NA -
- 152
-
imagen165 1H-RMN (CD3OD/400 MHz): 7,39(m, 2H), 7,25(t, 1H), 7,17(t,1H), 6,92(m, 1H), 5,02(m, 2H), 4,34(m, 1H), 3,96(d, 1H), 3,86(t, 1H), 3,70-3,40(m, 1H), 3,28(m, 1H), 2,32(m, 2H), 1,36(t, 3H). 385,5 13.500/68 TFA
- 153
-
imagen166 1H-RMN (CD3OD/400 MHz): 7,32 (m, 2H), 7,10(m, 2H), 6,98-6,51(m, 1H), 4,81(s, 2H), 4,40-4,00 (m, 1H), 1,79(m, 4H), 1,70-1,04(m, 6H). 370,5 19.000/5,7 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 154
-
imagen167 1H-RMN (CD3OD/400 MHz): 7,54-6,72(m, 5H), 5,04(s, 2H), 3,86(m, 2H), 3,35 (m, 6H), 1,33 (t, 6H). 384,5 1.430/100 TFA
- 155
-
imagen168 1H-RMN (CD3OD/400 MHz): 7,35(m, 2H), 7,19(m, 2H), 6,81(s, 1H), 5,03(s, 2H), 3,81(m, 2H), 3,26 (m, 2H), 3,10(q, 2H), 1,32 (t, 3H). 359,4 2.150/100 TFA
- 156
-
imagen169 1H-RMN (CD3OD/400 MHz): 7,66(m, 1H), 7,53(m, 1H), 7,27(m, 2H), 6,93(s, 1H), 4,56(s, 2H), 3,92(m, 2H), 3,51(m, 4H), 3,27(m, 2H), 1,91(m, 2H), 1,65(m, 2H), 1,05(t, 3H), 0,89 (t, 3H). 415,5 NA/NA TFA
- 157
-
imagen170 1H-RMN (CD3OD/400 MHz): 7,41(m, 2H), 7,23(m, 2H), 6,96(s, 1H), 5,10(s, 2H), 3,78(m, 4H), 3,24 (t, 2H), 1,34 (s, 12H). 415,5 NA/NA TFA
- 158
-
imagen171 1H-RMN (CD3OD/400 MHz): 7,34(m, 2H), 7,19(m, 2H), 6,81(s, 1H), 5,03(s, 2H), 4,20-3,40(m, 6H), 3,15 (m, 2H), 2,10 (m, 4H). 385,4 265/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 159
-
imagen172 1H-RMN (CD3OD/400 MHz): 7,49(m, 1H), 7,39(m, 3H), 6,72(s, 1H), 5,07(s, 2H), 3,89(m, 2H), 3,31 (m, 6H), 1,32 (t, 6H). 403,4 73/100 TFA
- 160
-
imagen173 1H-RMN (CD3OD/400 MHz): 9,24(m, 1H), 7,80(d, 1H), 7,61(t, 1H), 7,47(m, 1H), 7,33-6,72(m, 1H), 5,39(m, 2H), 3,94(m, 2H), 3,41 (m, 6H), 1,33 (t, 6H). 409,5 825/100 TFA
- 161
-
imagen174 1H-RMN (CD3OD/400 MHz): 7,45(d, 1H), 7,33(nd, 1H), 7,17(t, 1H), 7,00(d, 1H), 6,94(s, 1H), 6,37(m, 1H), 5,24(m, 2H), 3,88(m, 2H), 3,20-2,90 (m, 6H), 1,18 (t, 6H). 408,5 76/100 TFA
- 162
-
imagen175 1H-RMN (CD3OD/400 MHz): 7,52-7,22(m, 5H), 5,03(s, 2H), 3,85(m, 4H), 3,45(m, 2H), 3,13 (m, 2H), 2,10 (m, 4H). 401,4 107/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 163
-
imagen176 1H-RMN (CD3OD/400 MHz): 9,34(s, 1H), 7,79(d, 1H), 7,60(t, 1H), 7,44(m, 1H), 7,33-6,72(m, 1H), 5,38(m, 2H), 4,30-3,40(m, 6H), 3,17 (m, 2H), 2,09 (m, 4H). 407,4 1.085/100 TFA
- 164
-
imagen177 1H-RMN (CD3OD/400 MHz): 7,41(d, 1H), 7,31(nd, 1H), 7,14(t, 1H), 6,92(d, 1H), 6,78(s, 1H), 6,39(m, 1H), 5,20(s, 2H), 3,86(m, 2H), 3,70(m, 2H), 3,29(m, 2H), 3,01 (m, 2H), 2,02(m, 4H). 406,4 113/100 TFA
- 165
-
imagen178 1H-RMN (CD3OD/400 MHz): 7,55(m, 1H), 7,37(m, 1H), 7,29(d, 1H), 5,02(s, 2H), 3,83(m, 4H), 3,46(m, 2H), 3,15 (m, 2H), 2,10 (m, 4H). 435,4+437,4 45.000/50 TFA
- 166
-
imagen179 1H-RMN (CD3OD/400 MHz): 7,56(s, 1H), 7,36(m, 2H), 7,29-6,60(m, 1H), 5,04(s, 2H), 3,84(m, 2H), 3,32(m, 6H), 1,32(t, 6H). 437,4+439,4 NA/NA TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 167
-
imagen180 1H-RMN (CD3OD/400 MHz): 7,65-6,45(m, 4H), 4,96(m, 2H), 3,86(m, 2H), 3,30(m, 6H), 1,32(t, 6H). 437,4+439,4 186/100 TFA
- 168
-
imagen181 1H-RMN (CD3OD/400 MHz): 7,55-6,55(m, 4H), 4,92(m, 2H), 3,86(m, 2H), 3,30(m, 6H), 1,32(t, 6H). 437,4+439,4 97/100 TFA
- 169
-
imagen182 1H-RMN (CD3OD/400 MHz): 7.51(m, 2H), 7.41(m, 1H), 7.20(s, 1H), 5.32(s, 2H), 3.67(m, 2H), 3.21(m, 4H), 3.04(m, 2H), 1.24(t, 6H). 437,4+439,4 66/100 TFA
- 170
-
imagen183 1H-RMN (CD3OD/400 MHz): 7.36 (m, 2H), 7.21-6.68(m, 2H), 5.03(s,2H), 3.84(m, 2H), 3.32(m, 6H), 1.32(t, 6H). 421,4 505/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 171
-
imagen184 1H-RMN (CD3OD/400 MHz): 7,50(m, 1H), 7,28-6,50(m, 3H), 4,95(m, 2H), 3,87(m, 2H), 3,30(m, 6H), 1,33(t, 6H). 421,4 88/100 TFA
- 172
-
imagen185 1H-RMN (CD3OD/400 MHz): 7,43(m, 1H), 7,35(d, 1H), 7,20 (t, 1H), 7,16(s, 1H), 5,15(s, 2H), 3,71(m, 2H), 3,22(m, 4H), 3,12(m, 2H), 1,26(t, 6H). 421,4 94/100 TFA
- 173
-
imagen186 1H-RMN (CD3OD/400 MHz): 7.52-6.42(m, 5H), 4.97(s, 2H), 3.88(m, 2H), 3.68(m, 2H), 3.32(m, 2H), 2.97 (m, 2H), 1.96(m, 2H), 1.78(m, 3H), 1.54(m, 1H). 415,4 66/100 TFA
- 174
-
imagen187 1H-RMN (CD3OD/400 MHz): 7,52-6,42(m, 5H), 5,03(s, 2H), 4,20-3,45(m, 12H). 417,4 1.495/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 175
-
imagen188 1H-RMN (CD3OD/400 MHz): 7,45(m, 1H), 7,34(m, 3H), 6,87-6,44(m, 1H), 5,10(s, 2H), 3,82(m, 2H), 3,28 (m, 6H), 1,29 (t, 6H). 403,4+415,4 305/100 TFA
- 176
-
imagen189 1H-RMN (CD3OD/400 MHz): 7,47(m, 1H), 7,35(m, 3H), 6,80-6,32(m, 1H), 5,06(s, 2H), 3,83(m, 2H), 3,29 (m, 6H), 1,30 (t, 6H). 369,4 1.150/100 TFA
- 177
-
imagen190 1H-RMN (CD3OD/400 MHz): 7,41(m, 1H), 7,31 (m, 1H), 7,14(m, 2H), 5,19(s, 2H), 3,71(m, 4H), 3,33(m, 2H), 3,08(m, 2H), 2,08(m, 4H). 419,4 180/100 TFA
- 178
-
imagen191 1H-RMN (CD3OD/400 MHz): 7,48(m, 2H), 7,38(m, 1H), 7,18(s, 1H), 5,31(s, 2H), 3,64(m, 4H), 3,26(m, 2H), 3,25(m, 2H), 2,02(m, 4H). 435,4 126/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 179
-
imagen192 1H-RMN (CD3OD/400 MHz): 7,41(m, 1H), 7,32(m, 1H), 7,15(m,2H), 5,17(s, 2H), 3,73(m, 2H), 3,56(m, 2H), 3,18(m, 2H), 2,93(m, 2H), 1,92(m, 2H), 1,75(m, 3H), 1,48(m, 1H). 433,5 133/100 TFA
- 180
-
imagen193 1H-RMN (CD3OD/400 MHz): 7,48(m, 2H), 7,39(m, 1H), 7,18(s, 1H), 5,30(s, 2H), 3,68(m, 2H), 3,52(m, 2H), 3,10(m, 2H), 2,90(m, 2H), 1,90(m, 2H), 1,74(m, 3H), 1,48(m, 1H). 449,4 154/100 TFA
- 181
-
imagen194 1H-RMN (CD3OD/400 MHz): 7,46(m, 1H), 7,34(m, 2H), 7,27(m, 1H), 6,66(bs, 1H), 5,04(s, 2H), 4,04(m, 1H), 3,68(m, 4H), 3,24(m, 2H), 2,60 (m, 2H), 1,39 (d, 3H). 415,5 430/100 TFA
- 182
-
imagen195 1H-RMN (CD3OD/400 MHz): 7,39(m, 1H), 7,26(m, 1H), 7,17(d, 1H), 6,66(bs, 1H), 5,08(m, 2H), 3,86(m, 2H), 3,30(m, 6H), 1,32(t, 6H). 421,5 109/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 183
-
imagen196 1H-RMN (CD3OD/400 MHz): 7,34-6,66(m, 4H), 4,96(s, 2H), 3,85(m, 2H), 3,29(m, 6H), 1,31(t, 6H). 418,5 185/100 TFA
- 184
-
imagen197 1H-RMN (CD3OD/400 MHz): 7,41(m, 1H), 7,37(m, 1H), 7,24(m, 1H), 7,16(m, 1H), 6,54(bs, 1H), 5,01(s, 2H), 3,89(m, 2H), 3,31 (m, 6H), 2,99(m, 1H), 1,31 (t, 6H), 1,19(d, 6H). 411,5 1.950/85 TFA
- 185
-
imagen198 1H-RMN (CD3OD/400 MHz): 7,45(m, 1H), 7,33(m, 3H), 7,15-6,59(m, 1H), 4,99(s, 2H), 3,59(m, 2H), 3,18 (m, 6H), 2,01(m, 2H), 1,29 (t, 6H). 417,4 1750/53 TFA
- 186
-
imagen199 1H-RMN (CD3OD/400 MHz): 7,45(m, 1H), 7,33(m, 3H), 7,15-6,59(m, 1H), 4,97(s, 2H), 3,61(m, 2H), 3,16 (m, 6H), 2,88(s, 6H), 2,00 (m, 2H). 389,4 375/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 187
-
imagen200 1H-RMN (CD3OD/400 MHz): 7,47(m, 1H), 7,33(m, 3H), 6,61(bs, 1H), 5,04(bs, 2H), 3,87(t, 2H), 3,38 (t, 6H), 2,97(s, 6H). 375,4 295/100 TFA
- 188
-
imagen201 1H-RMN (CD3OD/400 MHz): 7,48(m, 1H), 7,33(m, 3H), 6,53(bs, 1H), 4,99(bs, 2H), 3,90(m, 2H), 3,59(m, 2H), 3,35(m, 2H), 2,52 (t, 2H), 1,88(m, 3H), 0,98(m, 7H). 443,5 46/60 TFA
- 189
-
imagen202 1H-RMN (CD3OD/400 MHz): 7,47(m, 1H), 7,34(m, 3H), 6,62(bs, 1H), 5,03(bs, 2H), 3,88(m, 2H), 3,56(m, 2H), 3,37(m, 2H), 3,25 (m, 2H), 1,93(m, 4H), 1,73(m, 4H). 429,4 24/100 TFA
- 190
-
imagen203 1H-RMN (CD3OD/400 MHz): 7,48(m, 1H), 7,33(m, 3H), 6,52(bs, 1H), 4,98(bs, 2H), 3,88(m, 2H), 3,71(m, 2H), 3,33(m, 2H), 2,97 (m, 2H), 1,93(m, 2H), 1,70(m, 1H), 1,44(m, 2H), 1,00 (d, 3H). 429,4 42/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 191
-
imagen204 1H-RMN (CD3OD/400 MHz): 7,48(m, 1H), 7,33(m, 3H), 6,50(bs, 1H), 4,97(bs, 2H), 3,90(m, 2H), 3,63(m, 2H), 3,33(m, 2H), 2,86 (t, 2H), 2,59 (t, 2H), 1,86 (m, 4H), 1,18(m, 1H), 1,00 (d, 3H). 429,4 29/100 TFA
- 192
-
imagen205 1H-RMN (CD3OD/400 MHz): 7,48(m, 1H), 7,33(m, 3H), 6,50(bs, 1H), 4,99(bs, 2H), 3,90(m, 2H), 3,62(m, 2H), 3,33(m, 2H), 2,05-1,20(m, 10H). 429,4 104/100 TFA
- 193
-
imagen206 1H-RMN (CD3OD/400 MHz): 7,40(m, 4H), 4,94(s, 2H), 3,76(m, 2H), 3,22(m, 6H), 1,26(t, 6H). 387,4 14.000/58 TFA
- 194
-
imagen207 1H-RMN (CD3OD/400 MHz): 7,18(m, 1H), 6,92-6,66(m, 3H), 4,87(bs, 2H), 3,81(m, 2H), 3,50(m, 2H), 3,28(m, 4H), 1,93(m, 4H), 1,73(s, 4H). 445,4 43/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 195
-
imagen208 1H-RMN (CD3OD/400 MHz): 7,10(m, 1H), 6,91(bs, 1H), 6,62(d, 1H), 6,57(d, 1H), 4,88(bs, 2H), 3,80(m, 2H), 3,51(m, 2H), 3,26(m, 4H), 1,91(m, 4H), 1,72(s, 4H). 429,5 95/100 TFA
- 196
-
imagen209 1H-RMN (CD3OD/400 MHz): 7,10(m, 1H), 6,73(m, 3H), 4,88(bs, 2H), 3,86(m, 2H), 3,54(m, 2H), 3,28(m, 4H), 1,92(m, 4H), 1,74(s, 4H). 444,4 99/100 TFA
- 197
-
imagen210 1H-RMN (CD3OD/400 MHz): 7,33(m, 2H), 7,18(m, 2H), 6,78(bs, 1H), 5,00 (bs, 2H), 3,85(m, 2H), 3,55(m, 2H), 3,37(m, 2H), 3,25(m, 2H), 1,91(m, 4H), 1,72(s, 4H). 413,4 63/100 TFA
- 198
-
imagen211 1H-RMN (CD3OD/400 MHz): 7,42(m, 1H), 7,10-6,95(m,32H), 5,09 (bs, 2H), 3,79(m, 2H), 3,51(m, 2H), 3,31(m, 2H), 3,21(m, 2H), 1,90(m, 4H), 1,72(s, 4H). 431,5 130/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 199
-
imagen212 1H-RMN (CD3OD/400 MHz): 7,49(m, 1H), 7,33(m, 3H), 6,50(bs, 1H), 4,97 (bs, 2H), 3,88(m, 2H), 3,70(m, 2H), 3,33(m, 2H), 2,97(m, 2H), 2,00(m, 2H), 1,38(m, 5H), 0,94(t, 3H). 443,5 100/100 TFA
- 200
-
imagen213 1H-RMN (CD3OD/400 MHz): 7,22(m, 1H), 6,74(m, 3H), 4,90 (bs, 2H), 3,88(m, 2H), 3,63(m, 2H), 3,31(m, 2H), 2,87(t, 1H), 2,59(t, 1H), 1,86(m, 4H), 1,18(m, 1H), 1,00(d, 3H). 444,5 130/100 TFA
- 201
-
imagen214 1H-RMN (CD3OD/400 MHz): 7,34(m, 2H), 7,18(m, 2H), 6,81(bs, 1H), 5,02 (bs, 2H), 3,86(m, 2H), 3,63(m, 2H), 3,31(m, 2H), 2,85(t, 1H), 2,58 (t, 1H), 1,85(m, 4H), 1,16(m, 1H), 0,98(d, 3H). 413,5 215/100 TFA
- 202
-
imagen215 1H-RMN (CD3OD/400 MHz): 7,23(m, 1H), 6,77(m, 3H), 4,94 (bs, 2H), 3,86(m, 2H), 3,76(m, 1H), 3,59(m, 1H), 3,39(m, 1H), 3,25(m, 2H), 3,05(t, 1H), 2,06-1,68(m, 5H), 1,57(m, 2H), 1,38(m, 3H). 444,4 395/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 203
-
imagen216 1H-RMN (CD3OD/400 MHz): 7,36(m, 2H), 7,18(m, 2H), 6,85(bs, 1H), 5,02 (bs, 2H), 3,86(m, 2H), 3,77(m, 1H), 3,59(m, 1H), 3,40(m, 1H), 3,26(m, 2H), 2,85(t, 1H), 2,58 (t, 1H), 2,22-1,68(m, 5H), 1,58(m, 2H), 1,36(m, 3H). 413,5 550/100 TFA
- 204
-
imagen217 1H-RMN (CD3OD/400 MHz): 7,48(m, 1H), 7,39(m, 3H), 6,74(bs, 1H), 5,07 (m, 2H), 3,86(m, 2H), 3,75(m, 1H), 3,25(m, 4H), 1,31(m, 9H). 417,4 880/53 TFA
- 205
-
imagen218 1H-RMN (CD3OD/400 MHz): 7,48(m, 1H), 7,32(m, 3H), 6,60(bs, 1H), 5,04(s, 2H), 3,92(m, 2H), 3,80-3,38(m, 6H), 2,38(m, 4H). 451,4 2.050/100 TFA
- 206
-
imagen219 1H-RMN (CD3OD/400 MHz): 7,32(m, 1H), 7,15(m, 2H), 6,92(m, 1H), 6,75(bs, 1H), 5,27(m, 2H), 3,88(t, 2H), 3,73(m, 2H), 3,33(t, 2H), 3,04 (m, 2H), 2,02(m, 4H). 424,4 136/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 207
-
imagen220 1H-RMN (CD3OD/400 MHz): 7,10(d, 1H), 6,84(m, 2H), 6,71(d, 1H), 4,89(s, 2H), 3,80(m, 2H), 3,49(m, 2H), 3,22(m, 4H), 1,90(m, 4H), 1,72(s, 4H). 444,4 170/75 TFA
- 208
-
imagen221 1H-RMN (CD3OD/400 MHz): 9,26(m, 1H), 7,77(m, 1H), 7,58(m, 1H), 7,44(bs, 1H), 7,32-6,78,(m, 1H), 5,45-5,07 (m, 2H), 4,35-3,82(m, 2H), 3,78-3,20(m, 6H), 1,92(s, 4H), 1,73(s, 4H). 435,5 125/100 TFA
- 209
-
imagen222 1H-RMN (CD3OD/400 MHz): 7,47(m, 1H), 7,37(m, 3H), 6,71(s, 1H), 5,05(s, 2H), 3,86(m, 2H), 3,50-3,20 (m, 4H), 3,13(m, 2H), 1,71(m, 2H), 1,30(t, 3H), 0,99 (t, 3H). 417,5 52/100 TFA
- 210
-
imagen223 1H-RMN (CD3OD/400 MHz): 7,83(m, 1H), 7,57(m, 3H), 7,28-6,40,(m, 1H), 5,45-4,90 (m, 2H), 3,90(m, 2H), 3,60(m, 2H), 3,46(m, 2H), 3,28(m,2H), 1,92(m, 4H), 1,74(s, 4H). 474,5 133/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 211
-
imagen224 1H-RMN (CD3OD/400 MHz): 7,89(m, 1H), 7,83(m, 1H), 7,63(m, 1H), 7,15(s, 1H), 5,24(bs, 2H), 3,75(m, 2H), 3,48(m, 2H), 3,27(m, 4H), 1,90(m, 4H), 1,73(s, 4H). 474,5 123/100 TFA
- 212
-
imagen225 1H-RMN (CD3OD/400 MHz): 7,49(m, 1H), 7,39(m, 3H), 6,76,(bs, 1H), 5,04(m, 2H), 3,75(m, 2H), 3,58-3,10 (m, 4H),2,01-1,25(m, 12H). 443,5 5.812/53 TFA
- 213
-
imagen226 1H-RMN (CD3OD/400 MHz): 7,10(t, 1H), 6,86(d, 1H), 6,67(bs, 1H), 6,60(d, 1H), 4,95(s, 2H), 3,86(t, 2H), 3,54(m, 2H), 3,31 (t, 2H), 3,22(m, 2H), 1,92(m, 4H), 1,73(m, 4H). 444,4 60/100 TFA
- 214
-
imagen227 1H-RMN (CD3OD/400 MHz): 7,40-6,70(m, 4H), 5,02(m, 2H), 3,86(m, 2H), 3,57(m, 2H), 3,40(m, 2H), 3,28(m, 2H), 1,92(m, 4H), 1,73(m, 4H). 428,5 153/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 215
-
imagen228 1H-RMN (CD3OD/400 MHz): 7,34(m, 1H), 7,18(m, 2H), 6,69(bs, 1H), 4,95(bs, 2H), 3,86(m, 5H), 3,56(m, 2H), 3,38(m, 2H), 3,28(m, 2H), 1,92(m, 4H), 1,73(bs, 4H). 440,5 1.185/100 TFA
- 216
-
imagen229 1H-RMN (CD3OD/400 MHz): 6,97(t, 1H), 6,89(m, 2H), 6,60(m, 1H), 4,97(s, 2H), 3,84(t, 2H), 3,52(m, 2H), 3,31(t, 2H), 3,22(m, 2H), 1,90(m, 4H), 1,72(m, 4H). 428,5 117/100 TFA
- 217
-
imagen230 1H-RMN (CD3OD/400 MHz): 7,04(t, 1H), 6,97 (d, 1H), 6,88(bs, 1H), 6,78(d, 1H), 4,96(s, 2H), 3,82(t, 2H), 3,62(s, 3H), 3,50(m, 2H), 3,23(m, 4H), 1,90(m, 4H), 1,72(m, 4H). 440,5 230/100 TFA
- 218
-
imagen231 1H-RMN (CD3OD/400 MHz): 7,52(d, 1H), 7,19(s, 1H), 7,09(t, 1H), 6,76 (d, 1H), 5,06(bs, 2H), 4,41-3,29(m, 6H), 3,06(m, 2H), 1,87(m, 4H), 1,72(m, 4H). 444,4 41/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 219
-
imagen232 1H-RMN (CD3OD/400 MHz): 7,47(m, 1H), 7,33(m, 3H), 6,60(bs, 1H), 5,03(bs, 2H), 4,12-3,81(m, 2H), 3,80-3,48(m, 2H), 3,36(m, 2H), 3,06 (m, 1H), 2,13(m, 1H), 1,94(m, 2H), 1,71 (m, 1H). 431,4 1.300/100 TFA
- 220
-
imagen233 1H-RMN (CD3OD/400 MHz): 7,47(m, 1H), 7,33(m, 3H), 6,61 (bs, 1H), 5,02(bs, 2H), 4,21-3,25(m, 7H), 3,19-2,62(m, 2H), 2,35-1,48 (m, 4H). 431,4 465/100 TFA
- 221
-
imagen234 1H-RMN (CD3OD/400 MHz): 7,43(m, 1H), 7,36(m, 2H), 7,13(m, 1H), 5,08(q, 2H), 4,40-4,00(m, 2H), 3,37(m, 3H), 2,04(m, 5H), 1,41 (d, 3H). 430,4 223/60 TFA
- 222
-
imagen235 1H-RMN (CD3OD/400 MHz): 7,50-6,68(m, 4H), 5,12(s, 2H), 4,20(t, 2H), 3,81(t, 2H), 3,43(m, 4H), 2,10(m, 4H). 416,5 56/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 223
-
imagen236 1H-RMN (CD3OD/400 MHz): 7,46-6,61(m, 4H), 5,08(m, 2H), 4,22-3,60(m, 2H), 3,14 (m, 2H), 2,98(m, 2H), 1,75(m, 1H), 1,58(m, 2H), 1,34(t, 1H), 1,22(t, 2H), 0,96 (m, 3H). 432,5 32/100 TFA
- 224
-
imagen237 1H-RMN (CD3OD/400 MHz): rotámeros 7,65-7,10(m, 4H), 5,16+4,41(s, 2H), 3,92+3,31(t, 2H), 3,16-3,01(m, 5H), 2,96(m, 4H), 2,88(t, 1H). 480,4 410/100 TFA
- 225
-
imagen238 1H-RMN (CD3OD/400 MHz): 7,49(m, 1H), 7,37(m, 2H), 7,14(m, 1H), 5,13(s, 2H), 4,22(m, 2H), 4,06(bs, 1H), 3,74(t, 2H), 3,25(m, 7H), 3,28(m, 4H), 2,14(m, 1H), 1,77 (m, 3H). 446,4 102/100 TFA
- 226
-
imagen239 1H-RMN (CD3OD/400 MHz): 7,50-7,12(m, 5H), 4,86 (m, 3H), 3,82 (m, 1H), 2,81 (m, 2H), 2,39 (m, 2H). 356,3 12.000/80 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 227
-
imagen240 1H-RMN (CD3OD/400 MHz): 7,61-7,22(m, 4H), 6,54(bs, 1H), 4,98 (m, 1H), 4,61(m, 1H), 4,45(m, 1H), 4,32(m, 1H), 4,00 (m, 1H), 3,83(m, 1H), 3,52(m, 1H), 3,07(m, 1H), 2,43 (m, 2H), 2,17 (m, 1H). 373,4 215/100 TFA
- 228
-
imagen241 1H-RMN (CD3OD/400 MHz): 7,42(m, 1H), 7,31(m, 3H), 7,15+6,59(bs, 1H), 4,89(m, 2H), 3,52(m, 5H), 2,74(m, 4H), 2,48(m, 1H), 1,60(m, 6H), 1,07 (m, 1H). 493,4 2.000/100 TFA
- 229
-
imagen242 1H-RMN (CD3OD/400 MHz): 7,50-6,90(m, 9H), 6,72-6,40(m, 1H), 4,87(s, 1H), 4,70(bs, 1H), 4,00-3,57(m, 2H), 2,89 (m, 2H). 408,4 NA/NA -
- 230
-
imagen243 1H-RMN (CD3OD/400 MHz): 7,42(m, 1H), 7,30(m, 3H), 6,99(d, 1H), 6,85(d, 1H), 6,78-6,42(m, 3H), 4,86(s, 1H), 4,74(bs, 1H), 3,72(m, 1H), 3,58(m, 1H), 2,78 (m, 2H). 424,4 12.000/100 -
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 231
-
imagen244 1H-RMN (CD3OD/400 MHz): 7,48(m, 1H), 7,33(m, 3H), 6,72(bs, 1H), 5,09 (m, 2H), 4,01(m, 1H), 3,71(m, 3H), 3,47(m, 1H), 3,22 (m, 1H), 3,10(m, 1H), 2,24(m, 1H), 2,07(m, 2H), 1,88 (m, 1H), 1,36 (t, 1H). 415,5 148/65 TFA
- 232
-
imagen245 1H-RMN (CD3OD/400 MHz): 7,56-7,20(m, 4H),, 6,49(bs, 1H), 4,99 (bs, 2H), 4,13(m, 1H), 3,76(m, 1H), 3,52(m, 1H), 3,40(m, 1H), 3,28 (m, 1H), 2,05(m, 3H), 1,73(m, 1H). 387,5 320/85 TFA
- 233
-
imagen246 1H-RMN (CD3OD/400 MHz): 7,53(m, 2H), 7,44(m, 1H), 7,37(m, 1H), 4,88 (m, 1H), 4,40(s, 2H), 4,10(m, 1H), 3,97(m, 1H), 3,77 (m, 1H), 3,57(m, 1H), 2,66(m, 1H), 2,52 (m, 1H). 388,4 930/75 TFA
- 234
-
imagen247 1H-RMN (CD3OD/400 MHz): 7,60-7,32(m, 3H), 7,20-6,66(m, 1H), 5,13+4,39(s, 2H), 5,05+4,94(bs, 1H), 4,56(m, 1H), 4,21+3,87(m, 1H), 3,64(m, 2H), 3,54 (m, 2H), 3,46(m, 2H), 2,26(m, 1H), 2,06 (m, 1H). 432,5 111/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 235
-
imagen248 1H-RMN (CD3OD/400 MHz): 7,60-7,32(m, 3H), 7,20-6,66(m, 1H), 5,12+4,37(s, 2H), 5,05+4,10(bs, 1H), 4,18(m, 1H), 4,20+3,84(m, 1H), 3,56(m, 2H), 3,50 (m, 2H), 3,41(m, 2H), 3,32(d, 3H), 2,06 (m, 2H). 446,5 133/100 TFA
- 236
-
imagen249 1H-RMN (CD3OD/400 MHz): 7,60-6,66(m, 4H), 5,20-4,45(m, 3H), 5,05+4,10(bs, 1H), 4,00-4,12(m, 1H), 3,80+3,52(m, 2H), 3,41(m, 2H), 3,23-2,78(m, 3H), 2,06(m, 2H), 1,82(m, 2H). 448,4 160,73 TFA
- 237
-
imagen250 1H-RMN (CD3OD/400 MHz): 7,60-6,66(m, 4H), 5,12+4,38(s, 2H), 5,00(m, 1H), 4,22(m, 1H), 3,80-2,80(m, 10H), 2,16-1,62 (m, 4H). 460,5 183/100 TFA
- 238
-
imagen251 1H-RMN (CD3OD/400 MHz): 7,60-6,66(m, 4H), 5,14+4,38(s, 2H), 5,07+3,10(bs, 1H), 4,24+3,92(m, 1H), 3,82(m, 4H), 3,51(m, 3H), 3,41(m, 1H), 3,36(m, 1H), 2,15(m, 2H). 446,5 116/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 239
-
imagen252 1H-RMN (CD3OD/400 MHz): 7,60-6,66(m, 4H), 5,13+4,39(s, 2H), 4,99(m, 1H), 4,25(m, 1H), 3,76(m, 1H), 3,56(m, 1H), 3,50-3,00(m, 6H), 2,14(m, 4H). 448,4 115/100 TFA
- 240
-
imagen253 1H-RMN (CD3OD/400 MHz): 7,58-6,35(m, 4H), 5,08(m, 2H), 4,22-3,60(m, 2H), 3,58-2,95(m, 6H), 1,69(m, 2H), 1,28(m, 3H), 0,97 (m, 3H). 416,5 68/100 TFA
- 241
-
imagen254 1H-RMN (CD3OD/400 MHz): 7,60-6,62(m, 4H), 5,55-4,97(m, 2H), 4,34(s, 1H), 4,19+3,80(m, 1H), 3,76-3,05(m, 7H), 2,30 (m, 2H). 434,4 125/100 TFA
- 242
-
imagen255 1H-RMN (CD3OD/400 MHz): 7,60-6,62(m, 4H), 5,55-4,97(m, 2H), 4,34(s, 1H), 4,19+3,80(m, 1H), 3,76-3,05(m, 7H), 2,30 (m, 2H). 434,4 465/100 TFA
- EJ.
- Estructura RMN ES-MS (M++1) PKM2 AC50 (nM)/Resp. máx.* (%) Nota†
- 243
-
imagen256 1H-RMN (CD3OD/400 MHz): 7,60-6,60(m, 4H), 5,16+4,24(s, 2H), 4,95(m, 1H), 4,19+3,85(m, 1H), 3,76-2,70(m, 7H), 2,08 (m, 6H). 462,4 106/100 TFA
- 244
-
imagen257 1H-RMN (CD3OD/400 MHz): 7,05 (m, 1H), 6,51 (m, 3H), 4,70 (m, 2H), 3,47 (m, 2H), 2,64 (s, 1H), 2,00 (s, 2H), 1,80 (m, 4H). 337,9 62/107 -
- 245
-
imagen258 1H-RMN (DMSO-d6/400 MHz): 13,84 (s, 1H), 9,87 (s, 1H), 7,05 (m, 1H), 6,58 (m, 3H), 4,56 (m, 2H), 3,46 (m, 2H), 2,55 (m, 1H), 1,90-1,54 (m, 6H). 382,1 35/100 -
- 246
-
imagen259 1H-RMN (CDCl3/400 MHz): 8,00 (s, 1H), 7,20 (m, 1H), 6,51 (m, 2H), 6,20 (m, 1H), 4,70 (m, 2H), 3,50 (m, 2H), 2,64 (m, 1H),1,99 (m, 2H), 1,85-1,79 (m, 5H), 0,93 (m, 2H), 0,70 (m, 2H) 344,2 92/85 -
- * Resp. máx. (%) representa el % de respuesta máxima en un ensayo bioquímico en comparación con la fructosa 1,6bisfosfato. † Indica la forma salina si es aplicable. TFA = ácido trifluoroacético
Se entiende que cualquier forma de realización de los compuestos de estructura (I), incluidas las estructuras (Ia), (lb) e (Ic), como se ha indicado anteriormente, y cualquiera de los sustituyentes específicos expuestos en la presente memoria (p. ej., R1-R23) en los compuestos de estructuras (I), (la), (lb) y (Ic), como se ha indicado anteriormente, se 5 pueden combinar independientemente con otras realizaciones y/o sustituyentes de compuestos de estructuras (I), (la) , (Lb) y (Ic) para formar realizaciones de las invenciones no expuestas específicamente anteriormente. Además, en el caso de que una lista de sustituyentes se liste para cualquier grupo R determinado en una realización y/o reivindicación determinada, se entiende que cada uno de los sustituyentes puede ser eliminado de la realización y/o reivindicación determinada y que la lista restante de sustituyentes se considerará que están dentro del alcance de la 10 invención. Se entiende que en la presente descripción, las combinaciones de sustituyentes y/o variables de las
- Indicación
- Estirpe celular Sensibilidad a serina Sensibilidad al ejemplo 1
- SW48
- Sensible >30 μM
- SW480
- Insensible 100 nM
- SW620
- Sensible 200 nM
- SW948
- Insensible >30 μM
- GIST
- Gist882 Insensible 800 nM
- Cabeza/Cuello
- Detroit562 Sensible 3 μM
- FaDu
- Sensible >30 μM
- Riñón
- 786-O Sensible >30 μM
- A498
- Insensible >30 μM
- Caki-1
- Insensible 80 nM
- ACHN
- Insensible 100 nM
- Hígado
- HepG2 Insensible >30 μM
- Pulmón
- A549 Sensible 100 nM
- H1299
- Insensible 600 nM
- NCI-H460
- Sensible 5 μM
- NCI-H647
- Sensible >30 μM
- NCI-H23
- Insensible N/A
- NCI-H522
- Insensible >30 μM
- NCI-H1975
- Sensible 90 nM
- NCI-H441
- Sensible N/A
- Melanoma
- Malme3M Insensible >30 μM
- Ovario
- OVCAR-3 Sensible 20 nM
- Skov3
- Sensible 8 μM
- Pancreático
- AsPC1 Sensible >30 μM
- Capan1
- Insensible >30 μM
- Capan2
- Sensible >30 μM
- Panc-1
- Insensible 14 nM
- Hs766T
- Insensible 300 nM
- PSN-1
- Sensible >30 μM
- MiaPaCa2
- Sensible 200 nM
- PL45
- Sensible >30 μM
- Próstata
- 22RV1 Insensible >30 μM
- Du145
- Insensible >30 μM
- LNCaP
- Sensible >30 μM
- PC3
- Sensible 100 nM
- Sarcoma
- HT1080 Sensible 50 nM
El porcentaje de viabilidad (CE50) de las células A549 y PC3 se ensayó frente a determinados compuestos ilustrativos según los procedimientos generales anteriores. Los resultados se presentan en la Tabla 5 y la figura 8.
Tabla 5. Viabilidad de las células A549 y PC3 en presencia de compuestos ilustrativos
Claims (4)
-
imagen1 imagen2 imagen3 imagen4 imagen5 R20 es alcoxi, hidroxilo o halo; y x es 0, 1, 2 o 3; o(Ic)imagen6 o un estereoisómero, sal o tautómero farmacéuticamente aceptable del mismo,10en donde: R21 y R22 son cada uno independientemente H o halo; 15 R23 es H o alquilo; eimagen7 - 15. El compuesto de la reivindicación 1, en donde el compuesto se selecciona del grupo que consiste en:
imagen8 109imagen9 imagen10 imagen11 imagen12 imagen13 114imagen14 imagen15 imagen16 imagen17 imagen18 119imagen19 imagen20 imagen21 imagen22 imagen23 - 16. Una composición farmacéutica que comprende un compuesto de una cualquiera de las reivindicaciones 1-15, oun estereoisómero o sal farmacéuticamente aceptable del mismo, y un vehículo, diluyente o excipiente 5 farmacéuticamente aceptable.
- 17. El compuesto deuna cualquiera delas reivindicaciones 1-15 o la composición dela reivindicación 16 para uso en un método de tratamiento de cáncer en un mamífero que lo necesite, preferiblemente en donde el cáncer es cáncer pulmonar.124
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US20120302609A1 (en) * | 2011-05-25 | 2012-11-29 | Dynamix Pharmaceuticals Ltd. | Pyrazolines for the Modulation of PKM2 |
WO2013005157A1 (en) | 2011-07-05 | 2013-01-10 | Lupin Limited | Sulfone derivatives and their use as pkm2 modulators for the treatment of cancer |
WO2014062838A2 (en) * | 2012-10-16 | 2014-04-24 | Tolero Pharmaceuticals, Inc. | Pkm2 modulators and methods for their use |
JP6362610B2 (ja) | 2012-11-08 | 2018-07-25 | アジオス ファーマシューティカルズ, インコーポレイテッド | 治療用化合物及び組成物並びにpkm2調節剤としてのそれらの使用 |
US9447054B2 (en) | 2014-01-15 | 2016-09-20 | Korea Institute Of Radiological & Medical Sciences | Anticancer supplement agent including benzo[D]oxazol derivative as effective ingredient |
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2013
- 2013-10-16 WO PCT/US2013/065296 patent/WO2014062838A2/en active Application Filing
- 2013-10-16 EP EP13847643.7A patent/EP2909181B1/en active Active
- 2013-10-16 ES ES13847643.7T patent/ES2644758T3/es active Active
- 2013-10-16 US US14/435,976 patent/US9394257B2/en active Active
- 2013-10-16 JP JP2015537799A patent/JP6243918B2/ja active Active
- 2013-10-16 DK DK13847643.7T patent/DK2909181T3/da active
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2016
- 2016-06-15 US US15/183,581 patent/US10207996B2/en active Active
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2017
- 2017-10-20 JP JP2017203963A patent/JP6526767B2/ja active Active
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2018
- 2018-10-01 JP JP2018186629A patent/JP2019023209A/ja not_active Withdrawn
- 2018-12-19 US US16/226,599 patent/US10472328B2/en active Active
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2019
- 2019-09-26 US US16/584,912 patent/US10766865B2/en active Active
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2020
- 2020-03-03 JP JP2020035657A patent/JP2020097631A/ja not_active Withdrawn
- 2020-03-03 JP JP2020035656A patent/JP2020105190A/ja not_active Withdrawn
- 2020-07-15 US US16/930,254 patent/US20210002233A1/en not_active Abandoned
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2021
- 2021-07-21 JP JP2021120679A patent/JP7128331B2/ja active Active
- 2021-08-06 JP JP2021129580A patent/JP2021181467A/ja active Pending
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US20170015631A1 (en) | 2017-01-19 |
US20210002233A1 (en) | 2021-01-07 |
US10472328B2 (en) | 2019-11-12 |
JP2021181467A (ja) | 2021-11-25 |
JP6243918B2 (ja) | 2017-12-06 |
JP2019023209A (ja) | 2019-02-14 |
US20150344436A1 (en) | 2015-12-03 |
US10207996B2 (en) | 2019-02-19 |
JP6526767B2 (ja) | 2019-06-05 |
US20190119219A1 (en) | 2019-04-25 |
EP2909181B1 (en) | 2017-08-09 |
JP2021176878A (ja) | 2021-11-11 |
EP2909181A4 (en) | 2016-03-23 |
US20200109120A1 (en) | 2020-04-09 |
US10766865B2 (en) | 2020-09-08 |
JP7128331B2 (ja) | 2022-08-30 |
WO2014062838A2 (en) | 2014-04-24 |
EP2909181A2 (en) | 2015-08-26 |
WO2014062838A3 (en) | 2014-10-16 |
JP2020097631A (ja) | 2020-06-25 |
JP2015536325A (ja) | 2015-12-21 |
US9394257B2 (en) | 2016-07-19 |
DK2909181T3 (da) | 2017-11-20 |
JP2018009036A (ja) | 2018-01-18 |
JP2020105190A (ja) | 2020-07-09 |
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