Kinase modulators based on pyrrolopyridine derivatives

one. Compound of the formula where lone and L2 independently mean bond, -S (O)n-, -O-, -NH-, substituted or unsubstituted Withone-WITHfivealkylene or substituted or unsubstituted 2-5 membered heteroalkylene, where n is an integer from 0 to 2, BUTone means a 6-membered substituted or unsubstituted aryl or a 6-membered substituted or unsubstituted heteroaryl, BUT2 means substituted aryl or substituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, Rone means halogen, -ORfive, -NR6R7, -C (Z) Reight, -S (O)wR9, -CN, -NO2, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Xone means -C (R2) =, -C (R2) (R3) -, -N =, -N (Rfour) -, -S- or -O-, R2 and R3 independently mean hydrogen, halogen, -ORfive, -NR6R7, -C (Z) Reight, -S (O)wR9, -CN, -NO2, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Rfour means hydrogen, -C (O) Reight, -S (O)2Relevensubstituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Z means N (R23), S or O, where R23 means hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl, w means an integer from 0 to 2, Rfive independently means hydrogen, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R6 and R7 independently mean hydrogen, -C (O) Rten, -S (O)2Relevensubstituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Rten and Releven independently mean hydrogen, -NR12R13substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R12 and R13 independently mean hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Reight independently means hydrogen, -NR14R15, -ORsixteensubstituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R14, R15 and Rsixteen independently mean hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R9 independently means hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and if w is 2, then R9 optionally means -NR17R18, R17 and R18 independently mean hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, with R6 and R7, R12 and R13, R14 and R15 and R17 and R18 independently and optionally, together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted 5-membered heteroaryl. 2. The compound according to claim 1, where aone means 6-membered substituted aryl or 6-membered substituted heteroaryl. 3. The compound according to claim 1, where aone means substituted phenyl, substituted pyridinyl, substituted pyrimidinyl, substituted benzodioxolyl, substituted benzimidazolyl or substituted indolyl. four. The compound according to claim 3, in which aone substituted by a halogen atom. five. The compound according to claim 1, in which aone substituted by phenyl. 6. The compound according to claim 1, in which aone means a group of the formula where x is an integer from 1 to 5, Rnineteen independently halogen, -ORfive, -NR6R7, -C (Z) Reight, -S (O)wR9, -CN, -NO2, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, moreover, two groups Rnineteen optionally together with the carbon atoms to which they are attached form a substituted or unsubstituted ring. 7. The compound according to claim 6, where the group Rnineteenattached in position 1, together with the group Rnineteenattached at position 2 form a substituted or unsubstituted ring. eight. The compound according to claim 6, where the group Rnineteenattached in position 2, together with the group Rnineteenattached at position 3 form a substituted or unsubstituted ring. 9. The compound according to claim 6, where two groups Rnineteen optionally, together with the carbon atoms to which they are attached, form a substituted or unsubstituted ring, wherein said substituted or unsubstituted ring means a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. ten. The compound according to claim 6, where Rnineteen independently means halogen, -NR6R7, -ORfive or substituted or unsubstituted alkyl. eleven. The compound of claim 10, where the group Rfive, R6 and R7 independently mean hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, where R6 and R7 optionally together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted 5-membered heteroaryl. 12. The compound of claim 10, where Rfive, R6 and R7 independently mean hydrogen or substituted or unsubstituted alkyl. 13. The compound of claim 10, where Rfive, R6 and R7 independently mean hydrogen or substituted or unsubstituted Cone-WITH6alkyl. 14. The compound according to claim 6, where x is 1, and the group Rnineteen attached in position 2. 15. The compound according to claim 6, where x is 1, and the group Rnineteen attached in position 1. sixteen. The compound according to claim 6, where x is an integer from 2 to 5, and at least one group Rnineteen attached in position 1. 17. The compound according to claim 6, where x is an integer from 2 to 5 and at least one group Rnineteen attached in position 2. 18. The compound according to claim 1, where a2 means substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl. nineteen. The compound according to claim 1, where a2 means substituted or unsubstituted phenyl, substituted or unsubstituted thiophenyl, substituted or unsubstituted pyridinyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted triazolyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted pyrazinyl or substituted or unsubstituted imidazolyl. 20. The compound according to claim 1, where a2 means a group of the formula where y is an integer from 0 to 4, R20 independently halogen, -ORfive, -NR6R7, -C (Z) Reight, -S (O)wR9, -CN, -NO2, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, moreover, two groups R20 optionally together with the carbon atoms to which they are attached form a substituted or unsubstituted ring, or R20 and Rone optionally together with the carbon atoms to which they are attached form a substituted or unsubstituted ring. 21. The compound according to claim 20, where R20 independently means halogen, -NR6 R7, -ORfive or substituted or unsubstituted alkyl. 22. The compound according to item 21, where the group Rfive, R6 and R7 independently mean hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein R6 and R7 optionally together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted 5-membered heteroaryl. 23. The compound according to item 21, where Rfive, R6 and R7 independently mean hydrogen or substituted or unsubstituted alkyl. 24. The compound according to item 21, where Rfive, R6 and R7 independently mean hydrogen or substituted or unsubstituted Cone-WITH6alkyl. 25. The compound according to claim 20, where y is 1, and the group R20 attached at position 3 '. 26. The compound according to claim 20, where y is 2, and the group R20 attached at position 3 'and position 4'. 27. The compound according to claim 1, where a2 means a group of the formula where y is an integer from 0 to 3, R20 independently halogen, -ORfive, -HR6R7, -C (Z) Reight, -S (O)wR9, -CN, -NO2, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, with R20 and Rone optionally together with the carbon atoms to which they are attached form a substituted or unsubstituted ring. 28. The compound of claim 27, wherein y is 1 and the group R20 attached at position 3 '. 29. The compound according to claim 1, where Lone means connection. thirty. The compound according to claim 1, where L2 means connection. 31. The compound according to claim 1, where Lone The compound according to claim 1, where Lone and L2 mean connection. 32. The compound according to claim 1, where Rone means -C (Z) Reight, Z means O, a Reight means -NR14R15. 33. The compound of claim 27, wherein Rone means -C (Z) Reight, Z means O, and Reight means -NR14R15. 34. Connection p, where Rone means -C (Z) Reight, Z means O, and Reight means -NR14R15. 35. The compound according to claim 1, where Rone means -C (Z) Reight, Z means O, and Reight means -NR14R15 and R14 and R15 independently mean substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or together with the nitrogen atom to which they are attached form a substituted or unsubstituted piperidinyl, substituted or unsubstituted piperazinyl, substituted or unsubstituted pyrrolidinyl, or substituted or unsubstituted morpholino. 36. The compound of claim 35, wherein y is 0. 37. Connection p, where R14 and R15 together with the nitrogen atom to which they are attached form piperazinyl substituted with substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl. 38. The compound according to clause 37, where the specified piperazinyl contains as a substituent a group of the formula - (CH2)t-NR21R22, where t is an integer from 0 to 6, and R21 and R22 independently mean hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, with R21 and R22 optionally together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heteroaryl. 39. The compound of claim 38, wherein R21 and R22 together with the nitrogen atom to which they are attached, form substituted or unsubstituted piperazinyl, substituted or unsubstituted piperidinyl or substituted or unsubstituted morpholino. 40. The compound of claim 38, wherein R21 and R22 independently mean hydrogen, substituted or unsubstituted alkyl, or unsubstituted or substituted aminoalkyl. 41. The compound according to claim 1, where aone substituted by at least one -OR groupfivewhere Rfive independently means hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 42. The compound according to claim 6, where a2 means a group of the formula where y is an integer from 0 to 4, R20 means halogen, -ORfive, -NR6R7, -C (Z) Reight, -S (O)wR9, -CN, -NO2, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, moreover, two groups R20 optionally together with the carbon atoms to which they are attached form a substituted or unsubstituted ring or R20 and Rone optionally together with the carbon atoms to which they are attached form a substituted or unsubstituted ring. 43. Connection p, where the group R20attached at position 3 ', together with the group Rone form a substituted or unsubstituted ring. 44. Connection p, where the group R20attached at position 3 ', together with the group R20attached at position 4 'form a substituted or unsubstituted ring. 45. Connection p, where Rone means -C (Z) Reight, Z means O, and Reight means -NR14R15, and R15 and R20 together with the carbon atom to which the R group is attached20and the nitrogen atom to which the R group is attached15form a substituted or unsubstituted ring. 46. Connection p, where Lone and L2 mean connection. 47. The compound of claim 42, wherein x is 1 and y is 0. 48. The compound of claim 47, wherein the group Rnineteen attached in position 1. 49. The compound of claim 47, wherein the group Rnineteen attached in position 2. 50. The compound of claim 42, wherein x is 2, y is 0, and the group Rnineteen attached in position 1 and 4. 51. The compound of claim 42, wherein x is 2, y is 0, and the group Rnineteen attached at position 1 and 5. 52. The compound according to claim 42, where x is 1, y is 1, the group R20 attached at position 3 ', and the group Rnineteen attached in position 1. 53. The compound according to claim 42, where x is 1, y is 2, the group R20 attached at position 3 'and 4', and the group Rnineteen attached in position 1. 54. The compound according to claim 42, where x is 2, y is 0, and one group Rnineteen attached in position 2. 55. The compound of claim 6, wherein A is a group of the formula where y is an integer from 0 to 3, R20 means halogen, -ORfive, -NR6R7, -C (Z) Reight, -S (O)wR9, -CN, -CF3, -NO2substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 56. The compound of claim 55, wherein y is 1 and the group R20 attached at position 3 '. 57. A method for modulating protein kinase activity, comprising contacting said protein kinase with a compound according to claim 1. 58. A method for modulating the activity of a protein kinase selected from the group consisting of Abelson tyrosine kinase, Ron receptor tyrosine kinase, Met receptor tyrosine kinase Fms, Aurora kinase 3, p21-activated kinase-4 and 3-phosphoinositol-dependent kinase-1, includes contacting said kinase with a compound of the formula where lone and L2 independently mean bond, -S (O)n-, -O-, -NH-, substituted or unsubstituted Withone-WITHfivealkylene or substituted or unsubstituted 2-5 membered heteroalkylene, where n is an integer from 0 to 2, and BUTone and A2 independently mean substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 59. The method of claim 58, wherein Lone and L2 independently mean bond, -S (O)n-, -O-, -NH-, unsubstituted Cone-WITHfivealkylene or unsubstituted 2-5 membered heteroalkylene. 60. The method of claim 58, wherein Lone and L2 mean connection. 61. The method of claim 58, wherein Aone and A2 independently mean substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl. 62. The method of claim 58, wherein Aone and A2 independently mean substituted or unsubstituted aryl or a 6-membered substituted or unsubstituted heteroaryl. 63. The method of claim 58, wherein BUT2 substituted by at least one —C (Z) R groupeightwhere Z means N (R23), S or O, where R23 means hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl, Reight independently means hydrogen, -NR14R15, -ORsixteensubstituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and R14, R15 and Rsixteen independently mean hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 64. The method of claim 63, wherein Z is O and R iseight means -NR14R15. 65. The method of claim 58, wherein said compound is a compound of claim 1. 66. The method of claim 58, wherein said kinase is a Bcr-Abl mutant kinase that is selected from the group consisting of M244V, L248V, G250E, G250A, Q252H, Q252R, Y253F, Y253H, E255K, E255V, D276G, F311L, T1515, T315N, T315N T315A, F317V, F317L, M343T, M351T, E355G, F359A, F359V, V379I, F382L, L387M, H396P, H396R, S417Y, E459K and F486S. 67. The method of claim 66, wherein said kinase is a mutant T315I kinase. 68. Cancer treatment method allergies asthma inflammation obstructive airway disease autoimmune diseases metabolic disorders infections diseases of the central nervous system, brain tumors obesity hematologic diseases degenerative neuralgic diseases, cardiovascular disease or disease associated with angiogenesis, neovascularization or vasculogenesis, in the subject in need of such treatment wherein said method comprises administering to a subject a therapeutically effective amount of a compound according to claim 1. 69. The method of claim 68, wherein said cancer is leukemia or a myeloproliferative disorder. 70. A method of treating cancer in a subject in need of such treatment, comprising administering to the subject a therapeutically effective amount of a compound of formula where lone and L2 independently mean bond, -S (O)n-, -O-, -NH-, substituted or unsubstituted Cone-WITHfivealkylene or substituted or unsubstituted 2-5 membered heteroalkylene, where n is an integer from 0 to 2, and BUTone and A2 independently mean substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 71. The method of claim 70, wherein said cancer is leukemia or a myeloproliferative disorder. 72. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula where lone and L2 independently mean bond, -S (O)n-, -O-, -NH-, substituted or unsubstituted Withone-WITH3alkylene or substituted or unsubstituted 2-5 membered heteroalkylene, where n is an integer from 0 to 2, and BUTone and A2 independently mean substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl. 73. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of the formula where lone and L2 independently mean bond, -S (O)n-, -O-, -NH-, substituted or unsubstituted Withone-WITHfivealkylene or a substituted or unsubstituted 2-5 membered heteroalkylene, and n is an integer from 0 to 2, BUTone means a 6-membered substituted or unsubstituted aryl or a 6-membered substituted or unsubstituted heteroaryl, BUT2 means substituted aryl or substituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl, Rone means halogen, -ORfive, -NR6R7, -C (Z) Reight, -S (O)wR9, -CN, -NO2, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Xone means -C (R2) =, -C (R2) (R3) -, -N =, -N (Rfour) -, -S- or -O-, R2 and R3 independently mean hydrogen, halogen, -ORfive, -NR6R7, -C (Z) Reight, -S (O)wR9, -CN, -NO2, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Rfour means hydrogen, -C (O) Reight, -S (O)2Relevensubstituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Z means N (R23), S or O, where R23 means hydrogen, substituted or unsubstituted alkyl or substituted or unsubstituted heteroalkyl, w means an integer from 0 to 2, Rfive independently means hydrogen, -CF3substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R6 and R7 independently mean hydrogen, -C (O) Rten, -S (O)2Relevensubstituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Rten and Releven independently mean hydrogen, -NR12R13substituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R12 and R13 independently mean hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, Reight independently means hydrogen, -NR14R15, -ORsixteensubstituted, unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R14, R15 and Rsixteen independently mean hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, R9 independently means hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl , substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, and if w is 2, then R9 optionally means -NR17R18, R17 and R18 independently mean hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, with R6 and R7, R12 and R13, R14 and R15, and R17 and R18 independently and optionally, together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted 5-membered heteroaryl.