Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
  • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
  • C07D307/92—Naphthofurans; Hydrogenated naphthofurans
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
  • A61P35/02—Antineoplastic agents specific for leukemia
• • 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
  • C07D405/02—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
• • 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
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
  • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
  • C07D407/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

• the present invention relates to novel water-soluble prodrugs of 2-acetylnaphtho [2, 3-b] furan-4, 9-dione, pharmaceutically acceptable salts thereof, or hydrates or solvates thereof useful as a medicament .
• the invention also relates to pharmaceutical compositions comprising a novel water-soluble prodrug of
• the invention relates to therapeutic agents or prophylactic agents, wherein the therapeutic agents or prophylactic agents comprise a novel water-soluble prodrug of 2-acetylnaphtho [2, 3-b] furan-4, 9-dione, a pharmaceutically acceptable salt thereof, or a hydrate or solvate thereof, or treating methods for treating cancer using the same.
• Cancer develops when abnormality in gene occurs by an action of radiation, ultra violet rays, carcinogen, virus, and the like. The number of deaths by cancer increases year by year, and cancer is currently the top cause of death in Japan.
• antitumor agents surgical operation, radiotherapy, immunotherapy, and the like are performed.
• Major antitumor agents act on any of metabolism of a nucleic acid precursor, DNA synthesis, RNA synthesis, or protein synthesis.
• such metabolic processes occur in not only cancer cells, but also normal cells . Therefore, many antitumor agents act on not only on cancer cells, but also on normal cells, and consequently a variety of side effects develop.
• molecular targeting agent is a pharmaceutical agent designed to target a molecule specifically expressed in each cancer. Therefore, it is believed that a molecular targeting agent has higher specificity to cancer cells than conventional antitumor agents, and has fewer side effects.
• molecular targeting agents although previous side effects are reduced, there are problems that new side effects are exhibited and alternatives of pharmaceutical agents are limited.
• the aforementioned antitumor agents were clinically used for the purpose of cancer therapy and prolonging the life of a cancer patient, there are still a number of unsolved problems including problems of side effects and the like as described above. Accordingly, it is recognized that the development of a novel antitumor agent is an important object in the future.
• CSC cancer having self-replication competence
• the CSC is closely related to the malignant transformation of cancer.
• major types of cancer in human such as breast cancer, colon cancer, lung cancer, hematological malignancy, and the like
• CSCs are identified.
• a CSC and a conventional cancer cell differentiated from the CSC are significantly different in biological characteristics.
• a CSC is shown to be important in continuous proliferation of malignant tumor, metastasis and recurrence of cancer, and its resistance to an antitumor agent.
• Non Patent Literature 1 One of the characteristics of CSCs is to have replication competence. Reliable methods established as a method of measuring replication competence of a cell include measurement of cancer cell sphere-forming ability in non-adhesion state in the absence of serum (Non Patent Literature 2) . A compound that inhibits not only the proliferation of a non-CSC cancer cell, but also cancer cell sphere-forming ability is possibly very useful as a novel antitumor agent.
• Non Patent Literature 3 discloses that the following quinone derivatives isolated from the extract of a plant of the Tabebuia genus in the Bignoniaceae family have antitumor activity:
• R 1 , R 2 , and R 3 are hydrogen atoms; R 1 and R 3 are hydrogen atoms, and R 2 is a hydroxyl group; R 1 is a hydroxyl group, and R 2 and R 3 are hydrogen atoms; R 1 and R 2 are hydrogen atoms, and R 3 is COCH 3 ; or R 1 and R 2 are hydrogen atoms, and R 3 is COC (CF 3 ) (OCH 3 ) C 6 H 5 ] .
• Patent Literature 1 describes the following compound having antitumor activity and suppressing cancer cell sphere-forming ability:
• R 1 is a hydrogen atom, a halogen atom, a cyano group, a nitro group, a trifluoromethyl group, a trifluoromethoxy group, an optionally substituted alkyl group, or the like
• R 3 is a hydrogen atom, a cyano group, an optionally substituted alkyl group, or the like
• R 7 is a hydrogen atom, a halogen atom, a cyano group, a nitro group, an optionally substituted alkyl group, or the like
• n is 1 to 4, with the proviso that when R 3 is not an amino group, R 7 is not a hydrogen atom and at least one of R 1 and R 7 is a halogen atom, an aryl group, or an optionally substituted aryl group] .
• Patent Literature 2 describes the following compound as a hydrophobic prodrug for oral administration that is administered as a non-crystalline compound:
• each R 1 is independently halogen, -NO 2 , -CN, -OR, -SR, -N + (R) 3 , -N(R) 2 , -C (O)R, C0 2 R, or the like
• each of R a and R b is independently a hydrogen atom, sodium, potassium, an amine cation, a Ci-i 2 aliphatic, or the like
• R c is a hydrogen atom, -N(R) 2 , -OR, -SR, a Ci-i 2 aliphatic, or the like
• R 4 is independently a hydrogen atom, halogen, -N0 2 , -OR, -SR, -N + (R) 3 , -
• Patent Literature 3 describes the following compound exhibiting antitumor activity against various drug-resistant cancer cells:
• each R 1 is independently halogen, -NO 2 , -CN, -OR, -SR, -N + (R) 3 , -N(R) 2 , -C (O)R, C0 2 R, or the like
• each of R a and R b is independently a hydrogen atom, sodium, potassium, an amine cation, a Ci-i 2 aliphatic, or the like
• R c is a hydrogen atom, -N(R) 2 , -OR, -SR, a Ci-i 2 aliphatic, or the like
• R 4 is independently a hydrogen atom, halogen, -N0 2 , -OR, -SR, -N + (R) 3 , -N
• Patent Literature 4 describes the following compound as a hydrophobic prodrug for parenteral administration that is administered as aqueous nanoparticle suspension:
• each R 1 is independently halogen, -NO 2 , -CN, -OR, -SR, -N + (R) 3 , -N(R) 2 , -C (O)R, C0 2 R, or the like
• R 2 is independently a hydrogen atom, halogen, -NO 2 , -OR, -SR, -N + (R) 3 , -N(R) 2 , -C (O)R, C0 2 R, or the like
• each of R 3 and R 5 is independently optionally substituted a Ci- 2 ialiphatic
• R 4 is independently halogen, -N0 2 , -CN, -OR, -SR, -N + (R) 3 , -N(R) 2 , -C (O)R, C0 2 R, or the like
• each R is independently a hydrogen atom, or an optionally substituted group selected from a Ci_i 2 aliphatic
• Non Patent Literature 4 Generally, for most hydrophobic prodrugs to be enzymatically converted to an activated form, since interspecies difference and individual difference in conversion to an activated form are observed, a problem of drug concentration estimation in clinical practice occurs (Non Patent Literature 4) .
• a prodrug for oral administration described in Patent Literature 2 after administration, is affected by a first-pass effect in a small intestine and a liver, which causes interspecies difference
• a prodrug for parenteral administration described in Patent Literature 4 although it is not affected by a first-pass effect in a small intestine and a liver, it is converted to an activated form by an in vivo enzyme, esterase, and accordingly interspecies difference and individual difference may be observed in conversion to an activated form.
• the present invention provides improvements for known hydrophobic prodrugs for oral administration that is administered as a non-crystalline compound, and hydrophobic prodrugs for parenteral administration that is administered as aqueous nanoparticle suspension.
• known prodrugs for oral administration are affected by a first-pass effect in an intestine and a liver after administration, which causes interspecies difference.
• known prodrugs for parenteral administration are intravenously administrable, they are not affected by a first-pass effect in an intestine and a liver.
• problems of interspecies difference and individual difference are concerned. Therefore, the present invention provides improvements for developing a prodrug compound that is hard to be affected by enzymatic conversion and exhibit slight interspecies difference and individual difference.
• the present invention provides an orally and intravenously administrable, water-soluble prodrug of 2-acetylnaphtho [2, 3-b] furan-4, 9-dione that is converted to an activated form in vivo via a route other than an enzymatic conversion, and provides a compound very useful as a novel anticancer agent.
• the present invention relates to a prodrug that has high water-solubility and is converted to an activated form without the need of an enzyme.
• a prodrug of the present invention is orally administrated, since the prodrug is dissolved in the stomach and subsequently converted to an activated form depending on pH in the following digestive tract, it is not affected by an in vivo enzyme, which causes interspecies difference and individual difference.
• it is intravenously administered, it is not affected by a first-pass effect in an small intestine and a liver, which causes interspecies difference and individual difference, and that is converted to an activated form depending from pH in the plasma and without depending on an enzyme. Therefore, none of Non Patent Literatures 1, 2, and 3 and Patent Literatures 1-4 discloses or suggests any compound represented by the following formula (1) .
• the present inventors intensively studied to provides improvements, and consequently found that a compound having a soluble side chain of a certain structure exhibits high water-solubility suitable for oral administration and intravenous administration, and additionally is converted to an active form by chemical conversion.
• the present inventors finally reached the completion of the present invention .
• the present invention is as described below.
• B is an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted 3- to 12-membered cyclic amino group, or a group represented by the following formula (B) :
• X is a single bond, an optionally substituted Ci-ioalkylene, an optionally substituted C3-iocycloalkylene, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocycle, an optionally substituted 3- to 12-membered cyclic aminyl linker group, an optionally substituted C 2 -ioalkenylene, an optionally substituted C2-ioalkynylene, an optionally substituted CVioarylene, or an optionally substituted Cs-ioheteroarylene,
• Y is a single bond, an oxygen atom, -OCO-, -OC0 2 -, -OCONR 4A -, -OSO 2 -, -OS0 2 NR 4A -, -CO-, -C0 2 -, -CONR 4A -, -NR 4A -, -NR 4A CO-, -NR 4A C0 2 -, -NR 4A CONR 4B - , -NR 4A S0 2 -, -NR 4A S0 2 0-, -NR 4A S0 2 NR 4B -, a sulfur atom, -SO-, -S0 2 -, -S0 2 0-, -S0 2 NR 4A -, or an optionally substituted 3- to 12-membered cyclic aminyl linker group,
• R 4A and R 4B are identical or different, and each independently a hydrogen atom, an optionally substituted Ci-ioalkyl group, an optionally substituted C 3 -i 0 cycloalkyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted C 2 -i 0 alkenyl group, an optionally substituted C2-ioalkynyl group, an optionally substituted C6-ioaryl group, or an optionally substituted Cs-ioheteroaryl group,
• Z is a single bond, an optionally substituted Ci-ioalkylene, an optionally substituted C3-iocycloalkylene, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocycle, an optionally substituted 3- to 12-membered cyclic aminyl linker group, an optionally substituted C 2 -i 0 alkenylene, an optionally substituted C 2 -ioalkynylene, an optionally substituted C 6 -ioarylene, or an optionally substituted Cs-ioheteroarylene,
• n 0 , 1 , or 2 ,
• V is -NHR 5 , an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, or an optionally substituted 3- to 12-membered cyclic amino group, wherein the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring, and
• R 5 is a hydrogen atom, an optionally substituted Ci-ioalkyl group, an optionally substituted C3-iocycloalkyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted C 2 -i 0 alkenyl group, an optionally substituted C 2 -ioalkynyl group, an optionally substituted C 6 -ioaryl group, or an optionally substituted C 5 -i 0 heteroaryl group, and wherein
• the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring, and
• R , R , and R J " are identical or different, and each independently a hydrogen atom, an optionally substituted Ci-ioalkyl group, an optionally substituted C 3 -i 0 cycloalkyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted C 2 -ioalkenyl group, an optionally substituted C 2 -ioalkynyl group, an optionally substituted C6-ioaryl group, or an optionally substituted C 5 -i 0 heteroaryl group;
• R 1 is a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, an optionally substituted amino group, an optionally substituted 3- to 12-membered cyclic amino group, an optionally substituted Ci- 6 alkyl group, an optionally substituted C3-iocycloalkyl group, an optionally substituted C 2 - 6 alkenyl group, an optionally substituted C 2 - 6 alkynyl group, an optionally substituted Ci- 6 alkoxy group, an optionally substituted C6-ioaryl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted Ci- 6 alkylcarbonyl group, an optionally substituted C3-iocycloalkylcarbonyl group, an optionally substituted C6-ioarylcarbonyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, a carboxyl group
• ⁇ ⁇ , , and T U are identical or different, and each independently a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, an optionally substituted amino group, an optionally substituted 3- to 12-membered cyclic amino group, an optionally substituted Ci- 6 alkyl group, an optionally substituted C3-iocycloalkyl group, an optionally substituted C6-ioaryl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted Ci- 6 alkoxy group, an optionally substituted C 3 -i 0 cycloalkoxy group, an optionally substituted C 6 -ioaryloxy group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclyloxy group, a carboxyl group, an optionally substituted Ci- 6 alkylcarbonyl group, an optionally substituted C3-iocycloalkylcarbony
• R 8 is an optionally substituted Ci-i 0 alkyl group.
• B is an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted 3- to 12-membered cyclic amino group, or a group represented by the following formula (B) :
• X is a single bond, an optionally substituted Ci-ioalkylene, an optionally substituted C3-iocycloalkylene, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocycle, an optionally substituted 3- to 12-membered cyclic aminyl linker group, an optionally substituted C 2 -i 0 alkenylene, an optionally substituted C 2 -i 0 alkynylene, an optionally substituted C 6 -ioarylene, or an optionally substituted C 5 -i 0 heteroarylene,
• Y is a single bond, an oxygen atom, -0C0-, -0C0 2 -, -0C0NR 4A -, -OSO 2 -, -OS0 2 NR 4A -, -CO-, -C0 2 -, -C0NR 4A -, -NR A - , -NR 4A C0-, -NR 4A C0 2 -, -NR 4A CONR 4B - , -NR 4A S0 2 -, -NR 4A S0 2 0-, -NR 4A S0 2 NR 4B -, a sulfur atom, -SO-, -S0 2 -, -S0 2 0-, -S0 2 NR 4A -, or an optionally substituted 3- to 12-membered cyclic aminyl linker group,
• R 4A and R 4B are identical or different, and each independently a hydrogen atom, an optionally substituted Ci-ioalkyl group, an optionally substituted C3-iocycloalkyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted C 2 -ioalkenyl group, an optionally substituted C 2 -ioalkynyl group, an optionally substituted C 6 -ioaryl group, or an optionally substituted C 5 -i 0 heteroaryl group,
• Z is a single bond, an optionally substituted Ci-i 0 alkylene, an optionally substituted C 3 -i 0 cycloalkylene, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocycle, an optionally substituted 3- to 12-membered cyclic aminyl linker group, an optionally substituted C 2 -ioalkenylene, an optionally substituted C2-ioalkynylene, an optionally substituted C6-ioarylene, or an optionally substituted Cs-ioheteroarylene,
• n 0 , 1 , or 2 ,
• V is -NHR 5 , an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, or an optionally substituted 3- to 12-membered cyclic amino group, wherein the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring, and
• R 5 is a hydrogen atom, an optionally substituted Ci-ioalkyl group, an optionally substituted C 3 -i 0 cycloalkyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted C 2 -i 0 alkenyl group, an optionally substituted C 2 -ioalkynyl group, an optionally substituted C 6 -ioaryl group, or an optionally substituted C 5 -i 0 heteroaryl group, and wherein
• the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring, and
• R , R , and R J " are identical or different, and each independently a hydrogen atom, an optionally substituted Ci-ioalkyl group, an optionally substituted C 3 -i 0 cycloalkyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted C 2 -ioalkenyl group, an optionally substituted C 2 -ioalkynyl group, an optionally substituted C 6 -ioaryl group, or an optionally substituted Cs-ioheteroaryl group;
• R 1 is a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, an optionally substituted amino group, an optionally substituted 3- to 12-membered cyclic amino group, an optionally substituted Ci-6alkyl group, an optionally substituted C3-iocycloalkyl group, an optionally substituted C 2 - 6 alkenyl group, an optionally substituted C 2 - 6 alkynyl group, an optionally substituted Ci- 6 alkoxy group, an optionally substituted C6-ioaryl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted Ci- 6 alkylcarbonyl group, an optionally substituted C3-iocycloalkylcarbonyl group, an optionally substituted C 6 -ioarylcarbonyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, a carboxyl group
• ⁇ ⁇ , , and T U are identical or different, and each independently a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, an optionally substituted amino group, an optionally substituted 3- to 12-membered cyclic amino group, an optionally substituted Ci_ 6 alkyl group, an optionally substituted C 3 -i 0 cycloalkyl group, an optionally substituted C 6 -ioaryl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted Ci- 6 alkoxy group, an optionally substituted C 3 -i 0 cycloalkoxy group, an optionally substituted C 6 -ioaryloxy group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclyloxy group, a carboxyl group, an optionally substituted Ci- 6 alkylcarbonyl group, an optionally substituted C3-iocycloal
• a substituent in the (7), (8), (9), (10), (11), (12), (13), (14), (15), and (16) is a group optionally substituted with one to five identical or different substituents each independently selected from the group consisting of
• R 6 and R 7 are identical or different, and each independently a hydrogen atom, or a Ci-ioalkyl group optionally substituted with one to two groups selected from the group consisting of a halogen atom and a carboxyl group, wherein R 6 and R 7 , when both are optionally substituted Ci-ioalkyl groups, may be taken together with the nitrogen atom to which they are attached to form a 3- to 12-membered cyclic amino group.
• a substituent in the (7), (8), (9), (10), (11), (12), (13), (14), (15), and (16) is a group optionally substituted with one to five identical or different substituents each independently selected from the group consisting of
• R 6 and R 7 are identical or different, and each independently a hydrogen atom, or a Ci-ioalkyl group optionally substituted with one to two groups selected from the group consisting of a halogen atom and a carboxyl group, wherein R 6 and R 7 , when both are optionally substituted Ci-ioalkyl groups, may be taken together with the nitrogen atom to which they are attached to form a 3- to 12-membered cyclic amino group.
• the optionally substituted Ci-ioalkyl group a substituent of the optionally substituted Ci-ioalkyl group, the optionally substituted Ci- 6 alkyl group, the optionally substituted C 3 -i 0 cycloalkyl group, the optionally substituted 3- to 10-membered monocyclic or polycyclic heterocyclic group, the optionally substituted C 2 -ioalkenyl group, the optionally substituted C 2 - 6 alkenyl group, the optionally substituted C 2 -ioalkynyl group, the optionally substituted C 2 - 6 alkynyl group, the optionally substituted C 6 -ioaryl group, the optionally substituted C 5 -i 0 heteroaryl group, the optionally substituted 3- to 10-membered cyclic amino group, the optionally substituted Ci-i 0 alkylene, the optionally substituted C 3 -i 0 cycloalkylene, the optionally substituted 3- to 12-membered monocyclic or poly
• a substituent in the (9) and (10) is a group optionally substituted with one to five identical or different substituents each independently selected from the group consisting of
• R 6 and R 7 are identical or different, and each independently a hydrogen atom, or a Ci-ioalkyl group optionally substituted with one to two groups selected from the group consisting of a halogen atom and a carboxyl group, wherein R 6 and R 7 , when both are optionally substituted Ci-ioalkyl groups, may be taken together with the nitrogen atom to which they are attached to form a 3- to 12-membered cyclic amino group.
• R 6 and R 7 are identical or different, and each independently a hydrogen atom, or a Ci-ioalkyl group optionally substituted with one to two groups selected from the group consisting of a halogen atom and a carboxyl group, wherein R 6 and R 7 , when both are optionally substituted Ci-ioalkyl groups, may be taken together with the nitrogen atom to which they are attached to form a 3- to 12-membered cyclic amino group.
• R 6 and R 7 are identical or different, and each independently a hydrogen atom, or a Ci-6alkyl group optionally substituted with one to two groups selected from the group consisting of a halogen atom and a carboxyl group, wherein R 6 and R 7 , when both are optionally substituted Ci- 6 alkyl groups, may be taken together with the nitrogen atom to which they are attached to form a 3- to 6-membered cyclic amino group.
• R 1 is a hydrogen atom, a halogen atom, a cyano group, a hydroxyl group, an optionally substituted amino group, an optionally substituted 3- to 12-membered cyclic amino group, an optionally substituted Ci- 6 alkyl group, an optionally substituted C 3 -i 0 cycloalkyl group, an optionally substituted C 2 - 6 alkenyl group, an optionally substituted C 2 - 6 alkynyl group, an optionally substituted Ci- 6 alkoxy group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclic group, an optionally substituted Ci- 6 alkylcarbonyl group, an optionally substituted C3-iocycloalkylcarbonyl group, an optionally substituted 3- to 12-membered monocyclic or polycyclic heterocyclylcarbonyl group, a carboxyl group,
• a 3- to 12-membered cyclic amino group (the cyclic amino group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci-6alkoxy group) ;
• Ci-6alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkoxy group, a C3-iocycloalkyl group, and a 3- to 12-membered cyclic amino group) ;
• Ci- 6 alkoxy group (the alkoxy group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, and a C 3 -i 0 cycloalkyl group) ;
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• Ci- 6 alkylcarbonyl group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkoxy group, a C3-iocycloalkyl group, and a 3- to 12-membered cyclic amino group) ;
• aminocarbonyl group (the amino is optionally substituted with one or two groups selected from the group consisting of
• Ci- 6 alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci-6alkoxy group) ,
• a C3-iocycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci-6alkoxy group) , and
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci- 6 alkoxy group) ) ; or
• Ci- 6 alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, and a C3-iocycloalkyl group) ,
• Ci- 6 alkoxy group (the alkoxy group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, and a C 3 -i 0 cycloalkyl group) ,
• Ci- 6 alkylcarbonyl group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, a C3-iocycloalkyl group, and a 3- to 12-membered cyclic amino group) , or
• amino group (the amino group is optionally substituted with one or two groups selected from the group consisting of
• Ci- 6 alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, a C6-ioaryl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group, which is optionally substituted with one to three Ci- 6 alkyl groups),
• Ci- 6 alkylcarbonyl group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group, which is optionally substituted with one to three Ci-6alkyl groups),
• a C3-iocycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci-6alkoxy group) , and
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci- 6 alkoxy group) ) ;
• a Ci- 6 alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C 3 -i 0 cycloalkyl group, a C 6 -ioaryl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a C 3 -i 0 cycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ; (9) a C6-ioaryl group (the aryl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci-6alkoxy group) ;
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a Ci-6alkoxy group (the alkoxy group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C3-iocycloalkyl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a C3-iocycloalkoxy group (the cycloalkoxy group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a C6-ioaryloxy group (the aryl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a 3- to 12-membered monocyclic or polycyclic heterocyclyloxy group (the heterocycle is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a Ci- 6 alkylcarbonyl group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C 3 -i 0 cycloalkyl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a C3-iocycloalkylcarbonyl group the cycloalkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci-6alkoxy group
• a C 6 -ioarylcarbonyl group (the aryl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a 3- to 12-membered monocyclic or polycyclic heterocyclylcarbonyl group (the heterocycle is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci- 6 alkoxy group) ;
• a Ci-6alkoxycarbonyl group (the alkoxy is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C3-iocycloalkyl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a C3-iocycloalkoxycarbonyl group (the cycloalkoxy is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• (22) a C 6 -ioaryloxycarbonyl group (the aryl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• (23) a 3- to 12-membered monocyclic or polycyclic heterocyclyloxycarbonyl group (the heterocycle is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• Ci-6alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkoxy group, and 3- to 12-membered monocyclic or polycyclic heterocyclic group, which is optionally substituted with one to three Ci- 6 alkyl groups),
• a C 3 -i 0 cycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci-6alkoxy group) , and
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci- 6 alkoxy group) ) ;
• Ci-6alkylthio group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C 3 -i 0 cycloalkyl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a C 3 -i 0 cycloalkylthio group (the cycloalkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• aryl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a 3- to 12-membered monocyclic or polycyclic heterocyclylthio group (the heterocycle is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci-6alkoxy group) ;
• a Ci_ 6 alkylsulfinyl group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C 3 -i 0 cycloalkyl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• cycloalkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a C6-ioarylsulfinyl group (the aryl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a 3- to 12-membered monocyclic or polycyclic heterocyclylsulfinyl group (the heterocycle is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• aminosulfinyl group (the amino is optionally substituted with one or two groups selected from the group consisting of
• Ci- 6 alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group, which is optionally substituted with one to three Ci- 6 alkyl groups),
• a C 3 -i 0 cycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci-6alkoxy group) , and
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ) ;
• a Ci-6alkylsulfonyl group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C3-iocycloalkyl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a C3-iocycloalkylsulfonyl group (the cycloalkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a C 6 -ioarylsulfonyl group (the aryl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• (41) a 3- to 12-membered monocyclic or polycyclic heterocyclylsulfonyl group (the heterocycle is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ;
• an aminosulfonyl group (the amino is optionally substituted with one or two groups selected from the group consisting of (a) a Ci-6alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group, which is optionally substituted with one to three Ci- 6 alkyl groups),
• a C 3 -i 0 cycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci- 6 alkoxy group) , and
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci- 6 alkoxy group) ) ; or
• amino group (the amino group is optionally substituted with one or two groups selected from the group consisting of
• Ci- 6 alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, and a Ci- 6 alkoxy group) ,
• Ci- 6 alkylcarbonyl group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, and Ci- 6 alkoxy group) ,
• a C 3 -i 0 cycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) , and
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci-6alkyl group, and a Ci-6alkoxy group) ) ;
• a Ci-6alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C3-iocycloalkyl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a C 3 -i 0 cycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a Ci- 6 alkoxy group (the alkoxy group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C 3 -i 0 cycloalkyl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• a Ci- 6 alkylcarbonyl group (the alkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C 3 -i 0 cycloalkyl group, a C 6 -ioaryl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group) ;
• a C3-iocycloalkylcarbonyl group (the cycloalkyl is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) ;
• aminocarbonyl group (the amino is optionally substituted with one or two groups selected from the group consisting of
• Ci- 6 alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkoxy group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group, which is optionally substituted with one to three Ci- 6 alkyl groups),
• a C 3 -i 0 cycloalkyl group (the cycloalkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci- 6 alkyl group, and a Ci- 6 alkoxy group) , and
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, a Ci_ 6 alkyl group, and a Ci- 6 alkoxy group) ) ; or
• an amino group (the amino group is optionally substituted with one or two groups selected from the group consisting of a Ci-6alkyl group and a Ci- 6 alkylcarbonyl group) ,
• Ci-6alkyl group (the alkyl group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, and a Ci- 6 alkoxy group) ,
• Ci- 6 alkoxy group (the alkoxy group is optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, and a Ci- 6 alkoxy group) ,
• R 8 is a Ci-ioalkyl group optionally substituted with one to three groups selected from the group consisting of a halogen atom, a hydroxyl group, -NR 6 R 7 , a Ci- 6 alkoxy group, a C3-iocycloalkyl group, a C 6 -ioaryl group, and a 3- to 12-membered monocyclic or polycyclic heterocyclic group.
• [Item 28] The compound according to any one of items 1 to 26, or a pharmaceutically acceptable salt thereof, wherein R 8 is a Ci-ioalkyl group optionally substituted with one to three groups selected from the group consisting of a halogen atom, -NR 6 R 7 , a Ci- 6 alkoxy group, and a C 3 -i 0 cycloalkyl group.
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• a 3- to 12-membered cyclic amino group (the cyclic amino group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ), or (3) a group represented by the formula (B) , wherein the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring.
• substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxy
• B is a 3- to 6-membered monocyclic heterocyclic group, a 3- to 6-membered cyclic amino group, or a group represented by the formula (B) ,
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• C3-iocycloalkylene (the cycloalkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• a 3- to 12-membered monocyclic or polycyclic heterocycle (the heterocycle is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ), or
• a 3- to 12-membered cyclic aminyl linker group (the cyclic aminyl linker group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) .
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -C0 2 R 6 ) ,
• C3-iocycloalkylene (the cycloalkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -C0 2 R 6 ) ,
• a 3- to 12-membered monocyclic or polycyclic heterocycle (the heterocycle is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -CO 2 R 6 ) , or
• a 3- to 12-membered cyclic aminyl linker group (the cyclic aminyl linker group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -CO 2 R 6 ) .
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -CO2R 6 ) ; or
• C3-iocycloalkylene (the cycloalkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -C0 2 R 6 ) .
• Y is a single bond, an oxygen atom, -OC0 2 -, -OCONR 4A -, -CONR 4A -, -NR 4A -, -NR 4A CO-, -NR 4A C0 2 -, -NR 4A CONR 4B - , -NR 4A S0 2 -, -NR 4A S0 2 NR 4B -, a sulfur atom, -S0 2 -, -S0 2 NR 4A -, or an optionally substituted 3- to 12-membered cyclic aminyl linker group.
• Y is a single bond, an oxygen atom, -CONR 4A -, -NR 4A CO-, or a sulfur atom.
• Y is a single bond, an oxygen atom, or -NR 4A - .
• Ci-ioalkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• C 3 -i 0 cycloalkylene (the cycloalkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• a 3- to 12-membered monocyclic or polycyclic heterocycle (the heterocycle is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci-6alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , - CO2R 6 , -CONR 6 R 7 , - S O2 R 6 , and -S0 2 NR 6 R 7 ),
• a 3- to 12-membered cyclic aminyl linker group (the cyclic aminyl linker group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci-6alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , - CO2R 6 , -CONR 6 R 7 , - S O2 R 6 , and -S0 2 NR 6 R 7 ),
• C6-ioarylene (the arylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci-6alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , - CO2R 6 , -CONR 6 R 7 , - S O2 R 6 , and -S0 2 NR 6 R 7 ), or
• C5-ioheteroarylene (the heteroarylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) .
• substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -C0 2 R b ) ,
• C3-iocycloalkylene (the cycloalkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -C0 2 R 6 ) ,
• a 3- to 12-membered monocyclic or polycyclic heterocycle (the heterocycle is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and - CO2R 6 ) , or
• a 3- to 12-membered cyclic aminyl linker group (the cyclic aminyl linker group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and - CO2R 6 ) .
• V is (1) -NHR 5 ,
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ), or
• a 3- to 12-membered cyclic amino group (the cyclic amino group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci-6alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) ; and
• 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring.
• a hydrogen atom (2) a Ci-ioalkyl group (the alkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a C 6 -ioaryl group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , -S0 2 NR 6 R 7 , -OC0 2 R 6 , -OCONR 6 R 7 , and -NR 6 C0 2 R 7 );
• a C 3 -i 0 cycloalkyl group (the cycloalkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci-6alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) ;
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci-6alkoxy group, a C 3 -scycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 );
• a C 6 -ioaryl group (the aryl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ); or
• a C 5 -i 0 heteroaryl group (the heteroaryl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -SO2 NR. R ) .
• Ci-ioalkyl group (the alkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , -CO 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• a C3-iocycloalkyl group (the cycloalkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) ,
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• a C 6 -ioaryl group (the aryl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ), or (6) a C5-ioheteroaryl group (the heteroaryl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alk
• Ci-ioalkyl group (the alkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -C0 2 R 6 ) ,
• a C3-iocycloalkyl group (the cycloalkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -C0 2 R 6 ) , or
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, -NR 6 R 7 , and -C0 2 R 6 ) .
• Ci-ioalkyl group (the alkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a C 6 -ioaryl group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , -S0 2 NR 6 R 7 , -OC0 2 R 6 , -OCONR 6 R 7 , and -NR 6 C0 2 R 7 ) .
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C3- 8 cycloalkoxy group, -NR 6 R 7 , -CO 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) ,
• a 3- to 12-membered cyclic amino group (the cyclic amino group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) , or
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• C3-iocycloalkylene (the cycloalkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) ,
• a 3- to 12-membered monocyclic or polycyclic heterocycle (the heterocycle is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ), or (5) a 3- to 12-membered cyclic aminyl linker group (the cyclic aminyl linker group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfon
• Y is a single bond, an oxygen atom, -CONR 4A -, -NR 4A CO-, or a sulfur atom,
• R 4A is a hydrogen atom, or a Ci- 6 alkyl group optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , and -CONR 6 R 7 ,
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 -scycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• C 3 -i 0 cycloalkylene (the cycloalkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) ,
• a 3- to 12-membered monocyclic or polycyclic heterocycle (the heterocycle is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C3- 8 cycloalkoxy group, -NR 6 R 7 , - CO2R 6 , -CONR 6 R 7 , - S O2 R 6 , and -S0 2 NR 6 R 7 ), or
• a 3- to 12-membered cyclic aminyl linker group (the cyclic aminyl linker group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , - CO2R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ),
• n 0 or 1
• ( 2 ) a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , - CO2R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ), or
• a 3- to 12-membered cyclic amino group (the cyclic amino group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ), wherein the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring,
• Ci-ioalkyl group (the alkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ) ,
• a C 3 -iocycloalkyl group (the cycloalkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a Ci- 6 alkoxy group, a C 3 - 8 cycloalkoxy group, -NR 6 R 7 , -C0 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , and -S0 2 NR 6 R 7 ), or
• R 6 and R 7 are identical or different, and each independently a hydrogen atom, or a Ci_ 6 alkyl group optionally substituted with one to two groups selected from the group consisting of a halogen atom and a carboxyl group, wherein R 6 and R 7 , when both are optionally substituted Ci_ 6 alkyl groups, may be taken together with the nitrogen atom to which they are attached to form a 3- to 12-membered cyclic amino group, and
• the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring, and R , R , and R are identical or different, and each independently a hydrogen atom, or a Ci-6alkyl group optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -CO 2 R 6 ;
• R 1 is a hydrogen atom
• R 2A , R 2B , R 2C , and R 2D are all hydrogen atoms.
• a 1 and A 2 are identical or different, and each independently -CO 2 B, -CONR B, or a hydrogen atom, wherein A 1 and A 2 are not both hydrogen atoms,
• a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -C0 2 R 6 ) , or
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -C0 2 R 6 ) ,
• a 3- to 12-membered cyclic aminyl linker group (the cyclic aminyl linker group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -C0 2 R 6 ) ,
• Y is a single bond or an oxygen atom
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -C0 2 R 6 ) ,
• a 3- to 12-membered cyclic aminyl linker group (the cyclic aminyl linker group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -C0 2 R 6 ) ,
• n 0 or 1
• ( 2 ) a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -C0 2 R 6 ) , or
• a 3- to 12-membered cyclic amino group (the cyclic amino group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -CO 2 R 6 ) , wherein the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring,
• Ci-6alkyl group (the alkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -CO2R 6 ) ,
• a C3-iocycloalkyl group (the cycloalkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -CO 2 R 6 ) , or
• ( 4 ) a 3- to 12-membered monocyclic or polycyclic heterocyclic group (the heterocyclic group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a carboxyl group, -NR 6 R 7 , and -C0 2 R 6 ) , and
• R 6 and R 7 are identical or different, and each independently a hydrogen atom, or a Ci_ 6 alkyl group optionally substituted with one to two groups selected from the group consisting of a carboxyl group, wherein R 6 and R 7 , when both are optionally substituted Ci_ 6 alkyl groups, may be taken together with the nitrogen atom to which they are attached to form a 3- to 6-membered cyclic amino group, and wherein
• the 3- to 12-membered monocyclic or polycyclic heterocyclic group and the 3- to 12-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring, and
• R i s a hydrogen atom, or a Ci_ 6 alkyl group optionally substituted with one to two groups selected from the group consisting of a carboxyl group and -CO 2 R 6 ;
• R 1 is a hydrogen atom
• R 2A , R 2B , R 2C , and R 2D are all hydrogen atoms.
• Ci- 6 alkylene (the alkylene is optionally substituted with one to three substituents selected from the group consisting of a carboxyl group and -CO 2 R 6 ) , or
• n 0 or 1 ;
• Ci-6alkyl group (the alkyl group is optionally substituted with one to three substituents selected from the group consisting of a halogen atom, a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a C6-ioaryl group, a Ci- 6 alkoxy group, a C3-scycloalkoxy group, -NR 6 R 7 , -CO 2 R 6 , -CONR 6 R 7 , -S0 2 R 6 , -S0 2 NR 6 R 7 , -OC0 2 R 6 , -OCONR 6 R 7 , and -NR 6 C0 2 R 7 ) , and
• R 6 and R 7 are identical or different, and each independently a hydrogen atom, or a Ci_ 6 alkyl group optionally substituted with one to two carboxyl groups, wherein R 6 and R 7 , when both are optionally substituted Ci_ 6 alkyl groups, may be taken together with the nitrogen atom to which they are attached to form a 3- to 12-membered cyclic amino group, and
• the 3- to 6-membered monocyclic heterocyclic group and the 3- to 6-membered cyclic amino group have at least one or more secondary nitrogen atoms in the ring, and
• R i s a hydrogen atom
• R 1 is a hydrogen atom
• R , R , R , and R ⁇ are all hydrogen atoms; and R 8 is a methyl group.
• X is a single bond, or Ci- 6 alkylene optionally substituted with one to two substituents selected from the group consisting of a carboxyl group and -CO 2 R 6 .
• B is a 3- to 6-membered monocyclic heterocyclic group, or a group represented by the formula (B) , wherein the 3- to 6-membered monocyclic heterocyclic group has at least one or more secondary nitrogen atoms in the ring.
• V is -NHR 5 .
• R 5 is a hydrogen atom, or Ci_ 6 alkyl optionally substituted with one to two substituents selected from the group consisting of a carboxyl group and -CO 2 .
• a 1 and A 2 are -CONHB
• B is a 3- to 6-membered monocyclic heterocyclic group, or a group represented by the formula (B) ,
• X is Ci- 6 alkylene optionally substituted with one to two substituents selected from the group consisting of a carboxyl group and -CO2 6 ,
• n 0 ,
• V is -NHR 5 or a 3- to 6-membered monocyclic heterocyclic group, wherein the 3- to 6-membered monocyclic heterocyclic group has at least one or more secondary nitrogen atoms in the ring,
• R 5 is a hydrogen atom, or a Ci- 6 alkyl group optionally substituted with one to two carboxyl groups, and
• R 6 is a Ci- 6 alkyl group
• the 3- to 6-membered monocyclic heterocyclic group has at least one or more secondary nitrogen atoms in the ring;
• R 1 is a hydrogen atom
• R 2A , R 2B , R 2C , and R 2D are all hydrogen atoms.
• a pharmaceutical composition comprising a compound according to any one of items 1 to 87, or a pharmaceutically acceptable salt thereof.
• a therapeutic agent and/or prophylactic agent for cancer wherein the agent comprises a compound according to any one of items 1 to 87, or a pharmaceutically acceptable salt thereof as an active ingredient, or the agent comprises a pharmaceutical composition according to item 88.
• the cancer is at least one type of cancer selected from the group consisting of acute leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, polycythemia vera, malignant lymphoma, brain tumor, head and neck cancer, esophageal cancer, thyroid cancer, small cell lung cancer, non-small-cell lung cancer, breast cancer, gastric cancer, gallbladder » bile duct cancer, hepatoma, pancreatic cancer, colon cancer, rectal cancer, chorioepithelioma, chorioblastoma, choriocarcinoma, endometrial cancer, cervical cancer, urothelial cancer, renal cell cancer, testicular tumor, Wilms' tumor, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, and soft tissue sarcoma.
• the cancer is at least one type of cancer selected from the group consisting of acute leukemia, chronic lymphoc
• a method for treating and/or preventing a cancer characterized by administering to a patient in need thereof a therapeutically and/or prophylactically effective amount of a compound according to any one of items 1 to 87, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition according to item 88 or a therapeutic agent and/or prophylactic agent according to item 89 or 90.
• the cancer is at least one type of cancer selected from the group consisting of acute leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, polycythemia vera, malignant lymphoma, brain tumor, head and neck cancer, esophageal cancer, thyroid cancer, small cell lung cancer, non-small-cell lung cancer, breast cancer, gastric cancer, gallbladder » bile duct cancer, hepatoma, pancreatic cancer, colon cancer, rectal cancer, chorioepithelioma, chorioblastoma, choriocarcinoma, endometrial cancer, cervical cancer, urothelial cancer, renal cell cancer, testicular tumor, Wilms' tumor, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, and soft tissue sarcoma.
• the cancer is at least one type of cancer selected from the group consisting of acute leukemia, chronic lymphoc
• the cancer is at least one type
• the cancer is at least one type of cancer selected from the group consisting of acute leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, polycythemia vera, malignant lymphoma, brain tumor, head and neck cancer, esophageal cancer, thyroid cancer, small cell lung cancer, non-small-cell lung cancer, breast cancer, gastric cancer, gallbladder » bile duct cancer, hepatoma, pancreatic cancer, colon cancer, rectal cancer, chorioepithelioma, chorioblastoma, choriocarcinoma, endometrial cancer, cervical cancer, urothelial cancer, renal cell cancer, testicular tumor, Wilms' tumor, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, and soft tissue
• a pharmaceutical composition for treating and/or preventing a cancer wherein the pharmaceutical composition comprises :
• composition comprising a first active substance consisting of a compound according to any one of items 1 to 87 or a pharmaceutically acceptable salt thereof; and (b) a composition comprising a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor.
• a pharmaceutical composition for treating and/or preventing a cancer comprising (a) a first active substance consisting of a compound according to any one of items 1 to 87 or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is characterized in that the first active substance is administered in combination with (b) a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor.
• a pharmaceutical composition for treating and/or preventing a cancer comprising (a) a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor, wherein the pharmaceutical composition is characterized in that the second active substance is administered in combination with (b) a first active substance consisting of a compound according to any one of items 1 to 87 or a pharmaceutically acceptable salt thereof.
• chemotherapeutic agent is an alkylating agent, an antimetabolite, a topoisomerase inhibiting drug, a DNA intercalator, an antimitotic agent, an anticancer antibiotic, a plant-derived anticancer agent, an epigenome drug, an immunomodulator, a molecule-targeting therapeutic drug, an angiogenesis inhibitor, or an other chemotherapeutic agent.
• the antimetabolite is a folic acid antagonist, a pyrimidine metabolism-inhibiting drug, a purine metabolism-inhibiting drug, a ribonucleotide reductase inhibiting drug, or a nucleotide analog.
• the pharmaceutical composition according to any one of items 97 to 105, wherein the topoisomerase inhibiting drug is selected from the group consisting of Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Anthracenedione, Mitoxantrone, Mitomycin C, Bleomycin, Dactinomycin, Plicamycin, Irinotecan, Camptothecin, Rubitecan, Belotecan, Etoposide, Teniposide, Topotecan, and Amsacrine.
• the topoisomerase inhibiting drug is selected from the group consisting of Doxorubicin, Daunorubicin, Epirubicin, Idarubicin, Anthracenedione, Mitoxantrone, Mitomycin C, Bleomycin, Dactinomycin, Plicamycin, Irinotecan, Camptothecin, Rubitecan, Belotecan, Etoposide, Teniposide, Topotecan, and Amsa
• the antimitotic agent is selected from the group consisting of Paclitaxel, DHA Paclitaxel, Paclitaxel Polyglutamate, Nab-paclitaxel , Paclitaxel Micelle, 7 -Glucosyloxyacetylpaclitaxel , BMS-275183, Docetaxel, Vinorelbine, Vincri
• the anticancer antibiotic is selected from the group consisting of Actinomycin D, Actinomycin C, Mitomycin C, Chromomycin A3, Bleomycin hydrochloride, Bleomycin sulfate, Peplomycin
• composition according to any one of items 97 to 109, wherein the plant-derived anticancer agent is selected from the group consisting of Etoposide, Etoposide phosphate, Vinblastine sulfate, Vincristine sulfate, Vindesine sulfate, Teniposide, Paclitaxel, Docetaxel, DJ-927, Vinorelbine, Irinotecan, and Topotecan .
• the plant-derived anticancer agent is selected from the group consisting of Etoposide, Etoposide phosphate, Vinblastine sulfate, Vincristine sulfate, Vindesine sulfate, Teniposide, Paclitaxel, Docetaxel, DJ-927, Vinorelbine, Irinotecan, and Topotecan .
• molecule-targeting therapeutic drug is selected from the group consisting of a kinase inhibitor, a proteasome inhibitor, a monoclonal antibody, a mTOR inhibitor, a TNF inhibiting drug, and a T-cell inhibiting drug.
• kinase inhibitor is a tyrosine kinase inhibitor, a serine/threonine kinase inhibitor, a Raf kinase inhibitor, a CDK inhibitor, or a MEK inhibitor.
• kinase inhibitor is selected from the group consisting of Imatinib, Gefitinib, Erlotinib, Afatinib, Dasatinib, Bosutinib, Vandetanib, Sunitinib, Axitinib, Pazopanib, Lenvatinib, Lapatinib, Nintedanib, Nilotinib, Crizotinib, Ceritinib, Alectinib, Ruxolitinib, Tofacitinib, Ibrutinib, Sorafenib, Vemurafenib, Dabrafenib, Palbociclib, Trametinib, Regorafenib, Cediranib, Lestaurtinib, Vandetinib, Vatalanib, Seliciclib, Tivantinib, Canertinib, Pelit
• the monoclonal antibody is selected from the group consisting of an anti-CD22 antibody, an anti-CD20 antibody, an anti-CD25 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD5 antibody, an anti-CD52 antibody, an anti-epidermal growth factor receptor antibody, an anti-endothelial cell growth factor antibody, an anti-TNF- antibody, an anti-IL-1 receptor antibody, an anti-IL-2 receptor antibody, an anti-IL-5 receptor antibody, an anti-IL-6 receptor antibody, an anti-HER2 antibody, an anti-IgE antibody, an anti-IgG antibody, an anti-RS virus antibody, an anti-CCR4 antibody, an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-RANKL antibody, or an anti-c-Met antibody.
• the monoclonal antibody is selected from the group consisting of an anti-CD22 antibody, an anti-CD20 antibody, an anti-CD25 antibody, an anti-CD30 antibody, an anti-CD33 antibody, an anti-CD5
• angiogenesis inhibitor is selected from the group consisting of CM101, IFN- , IL-12, platelet factor-4, Suramin, Semaxanib, Thrombospondin, a VEGFR antagonist, an angiogenesis inhibiting steroid plus heparin, cartilage-derived angiogenesis inhibitory factor, a matrix metalloproteinase inhibitor, Batimastat, Marimastat, Angiostatin, Endostatin, 2-methoxyestradiol, Tecogalan, Thrombospondin, an ⁇ 3 inhibitor, Linomide, and ADH-1.
• the pharmaceutical composition according to any one of items 97 to 123, wherein the "hormonal therapeutic agent" is selected from the group consisting of Fosfestrol, Diethylstilbestrol , Fluoxymesterone, Chlorotrianisene, Medroxyprogesterone acetate, Megestrol acetate, Chlormadinone acetate, Cyproterone acetate, Danazol, Dienogest, Asoprisnil, Allylestrenol , Gestrinone, Nomegestrol, Tadenan, Mepartricin, Raloxifene,
• the hormoneal therapeutic agent is selected from the group consisting of Fosfestrol, Diethylstilbestrol , Fluoxymesterone, Chlorotrianisene, Medroxyprogesterone acetate, Megestrol acetate, Chlormadinone acetate, Cyproterone acetate, Danazol, Dienogest, Asoprisnil, Allylestrenol
• Ormeloxifene Levormeloxifene, Tamoxifen citrate, Toremifene citrate, Idoxifene, a pill formulation, Mepitiostane, Testololactone, Aminoglutethimide,
• the immunotherapeutic agent is selected from the group consisting of Picibanil, Krestin, Schizophyllan, Lentinan, Ubenimex, an interferon, an interleukin, macrophage colony stimulating factor, granulocyte colony stimulating factor, erythropoietin, lymphotoxin, BCG vaccine, Corynebacterium par
• the pharmaceutical composition according to any one of items 97 to 125, wherein the biological agent is selected from the group consisting of Interleukin-2 , Interferon- , Interferon- ⁇ , Interferon- ⁇ , Erythropoietin, Filgrastim, granulocytes, Sargramostim, IL13-PE38QQR, Bacillus Calmette-Guerin, Levamisole, Octreotide, CPG7909, Provenge, GVAX, Myvax, Favld, Lenalidomide, Trastuzumab, Rituximab, Gemtuzumab ozogamicin, Alemtuzumab, Endostatin, Ibritumomab tiuxetan, Tositumomab, Cetuximab, Zanolimumab, Ofatumumab, HGS-ETR1, Pertuzumab, M200, SGN-30, Matuzumab,
• the cell growth factor inhibitor is selected from the group consisting of a epidermal growth factor inhibitor, an insulin - like growth factor inhibitor, a nerve growth factor inhibitor, a brain - derived neurotrophic factor inhibitor, an endothelial cell growth factor inhibitor, a colony stimulating factor inhibitor, a platelet - derived growth factor inhibitor, an Erythropoietin inhibitor, a fibroblast growth factor inhibitor, a hepatocyte growth factor inhibitor, a heregulin inhibitor, and an Angiopoietin inhibitor.
• the cell growth factor inhibitor is selected from the group consisting of a epidermal growth factor inhibitor, an insulin - like growth factor inhibitor, a nerve growth factor inhibitor, a brain - derived neurotrophic factor inhibitor, an endothelial cell growth factor inhibitor, a colony stimulating factor inhibitor, a platelet - derived growth factor inhibitor, an Erythropoietin inhibitor, a fibroblast growth factor inhibitor, a hepatocyte growth factor inhibitor, a heregulin inhibitor,
• the cell growth factor receptor inhibitor is selected from the group consisting of an epidermal growth factor receptor inhibitor, an insulin-like growth factor receptor inhibitor, a nerve growth factor receptor inhibitor, a brain-derived neurotrophic factor receptor inhibitor, an endothelial cell growth factor inhibitor, a colony stimulating factor inhibitor, a platelet-derived growth factor receptor inhibitor, an Erythropoietin receptor inhibitor, a fibroblast growth factor receptor inhibitor, a hepatocyte growth factor receptor inhibitor, a heregulin receptor inhibitor, and an Angiopoietin receptor inhibitor.
• the second active substance is selected from the group consisting of Cisplatin, Oxaliplatin, Temozolomide, Pemetrexed, Fluorouracil , Capecitabine, Gemcitabine, Leucovorin, Bortezomib, Irinotecan, Paclitaxel, Imat
• the cancer is at least one type of cancer selected from the group consisting of acute leukemia, chronic lymphocytic leukemia, chronic myelocytic leukemia, polycythemia vera, malignant lymphoma, brain tumor, head and neck cancer, esophageal cancer, thyroid cancer, small cell lung cancer, non-small-cell lung cancer, breast cancer, gastric cancer, gallbladder » bile duct cancer, hepatoma, pancreatic cancer, colon cancer, rectal cancer, chorioepithelioma, chorioblastoma, choriocarcinoma, endometrial cancer, cervical cancer, urothelial cancer, renal cell cancer, testicular tumor, Wilms' tumor, skin cancer, malignant melanoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, and soft tissue sarcoma.
• the cancer is at least one type of cancer selected from the group consisting of acute leukemia, chronic lymphoc
• a method for treating and/or preventing a cancer in a subject in need thereof comprising:
• a step of administering to the subject a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor .
• a method for treating and/or preventing a cancer in a subject in need thereof comprising a step of administering to the subject (a) a first active substance consisting of a compound according to any one of items 1 to 87 or a pharmaceutically acceptable salt thereof in combination with (b) a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor.
• first active substance and the second active substance are administered in therapeutically and/or prophylactically effective amounts.
• the amount of the first active substance administered and/or the amount of the second active substance administered are less than a therapeutically and/or prophylactically effective amount when administered alone, however, both are administered in therapeutically and/or prophylactically effective amounts when they are combined .
• the cancer is at least one type of
• a combination for treating and/or preventing a cancer comprising:
• a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor.
• a first active substance consisting of a compound according to any one of items 1 to 87 or a pharmaceutically acceptable salt thereof, for treating and/or preventing a cancer, characterized in that the first active substance is administered in combination with (b) a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor .
• a second active substance selected from the group consisting of a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor, for treating and/or preventing a cancer, characterized in that the second active substance is administered in combination with (b) a first active substance consisting of a compound according to any one of items 1 to 87 or a pharmaceutically acceptable salt thereof.
• a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor,
• a first active substance consisting of a compound according to any one of items 1 to 87 or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for treating and/or preventing a cancer, characterized in that the first active substance is administered in combination with (b) a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor .
• a second active substance selected from the group consisting of a chemotherapeutic agent, a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor .
• a second active substance selected from the group consisting of a hormonal therapeutic agent, an immunotherapeutic agent, a biological agent, a cell growth factor inhibitor, and a cell growth factor receptor inhibitor, in the manufacture of a medicament for treating and/or preventing a cancer, characterized in that the second active substance is administered in combination with (b) a first active substance consisting of a compound according to any one of items 1 to 87 or a pharmaceutically acceptable salt thereof.
• the present invention also provides treatment methods, prevention or prophylaxis methods, uses, and the like using a compound of the present invention, or a pharmaceutically acceptable salt thereof, a pharmaceutical composition thereof, a therapeutic agent, or a prophylactic agent, and further details and embodiments of these methods and uses can be understood by those skilled in the art from the description of the present specification.
• 2-acetylnaphtho [2, 3-b] furan-4, 9-dione targets a cancer stem cell in addition to a conventional cancer cell, it is expected as a novel anticancer agent.
• 2-acetylnaphtho [2, 3-b] furan-4, 9-dione has high crystallizability, its absorption in oral administration is an object as well as its use in parenteral administration has been limited.
• the compound represented by formula (1A) or (1) or a pharmaceutically acceptable salt thereof is a water-soluble prodrug of
• the compound of the present invention may be present in the form of a hydrate and/or a solvate, hydrates and/or solvates of the compound represented by formula (1A) or (1) or a pharmaceutically acceptable salt thereof are also encompassed by the present compound.
• the compound represented by formula (1A) or (1) may have one, or optionally one or more, asymmetric carbon atom(s), and may result in geometrical isomerism or axial chirality, it may be present as several types of stereoisomers. In the present invention, these stereoisomers, and mixtures and racemates thereof are also encompassed by the present compound.
• the number of substituents of a group defined by “optionally substituted” or “substituted” is not particularly limited if it is substitutable, and is one or plural.
• the description for each group is also applied when the group is one part of or a substituent on other groups .
• substituents in the present invention include a hydroxyl group, a carboxyl group, a sulfinate group, a sulfonate group, a phosphate group, a guanidine group, a cyano group, a nitro group, a halogen atom, an alkyl group, an alkylthio group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkylcarbonyl group, a cycloalkylsulfinyl group, an alkoxy group, a cycloalkoxy group, an alkoxycarbonyl group, an alkylcarbonyl group, an aryl group, an arylcarbonyl group, a heteroaryl group, a heterocyclic group, an amino group, an aminocarbonyl group, an aminosulfinyl group, an aminosufonyl group, a heterocyclyloxy group, a heterocyclyl
• halogen atom examples include a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom.
• a fluorine atom or a chlorine atom.
• a fluorine atom is a fluorine atom.
• alkyl group means a linear or branched, saturated hydrocarbon group, and for example, a "Ci- 4 alkyl group” or a “C6 alkyl group” means an alkyl group having one to four or six carbon atoms. The same applies to cases of other numbers .
• a “Ci-ioalkyl group” includes, preferably a "Ci-6alkyl group", and further preferably a "Ci- 4 alkyl group”.
• Specific examples of the "Ci-ioalkyl group” include, for example, a methyl group, an ethyl group, a propyl group, a 1-methylethyl group, a butyl group, a 2-methylpropyl group, a 1-methylpropyl group, a 1 , 1-dimethylethyl group, a pentyl group, a 3-methylbutyl group, a 2-methylbutyl group, a 2 , 2-dimethylpropyl group, a 1-ethylpropyl group, a 1 , 1-dimethylpropyl group, a hexyl group, a 4-methylpentyl group, a 3-methylpentyl group, a 2-methylpentyl group, a 1-methylpentyl group, a
• Ci-6alkyl group examples of those having one to six carbon atoms in the specific examples of the "Ci-ioalkyl group”.
• Ci- 4 alkyl group examples of those having one to four carbon atoms in the specific examples of the "Ci-ioalkyl group”.
• Ci- 6 alkylsulfinyl group and the “Ci- 6 alkylsulfonyl group” is defined the same as the above-described "Ci- 6 alkyl group”.
• Specific examples of the "Ci- 6 alkylthio group” include, for example, a methylthio group and the like .
• Specific examples of the "Ci- 6 alkylsulfinyl group” include, for example, a methylsulfinyl group and the like.
• Specific examples of the "Ci- 6 alkylsulfonyl group” include, for example, a methylsulfonyl group and the like.
• a “C2-ioalkenyl group” means a linear or branched, unsaturated hydrocarbon group having two to ten carbon atoms and containing one to five double bonds.
• Examples of the "C 2 -ioalkenyl group” include, preferably, a "C 2 - 6 alkenyl group”.
• C 2 -ioalkenyl group examples include, for example, a vinyl group, a propenyl group, a methylpropenyl group, a butenyl group, a methylbutenyl a group, a pentenyl group, a hexenyl group, a heptenyl group, a octenyl group, a nonenyl group, a decenyl group, and the like .
• a "C 2 -ioalkynyl group” means a linear or branched, unsaturated hydrocarbon group having two to ten carbon atoms and containing one triple bond.
• the "C 2 -ioalkynyl group” includes, preferably, a "C 2 - 6 alkynyl group”.
• C 2 -ioalkynyl group examples include, for example, propynyl, methylpropynyl , butynyl, methylbutynyl , a pentynyl group, a hexynyl group, a heptynyl group, an octynyl group, a nonynyl group, a decynyl group, and the like.
• a "Ci-ioalkylene” means a linear or branched, saturated hydrocarbon having one to ten carbon atoms .
• the "Ci-ioalkylene” includes, preferably, “Ci- 6 alkylene” .
• Specific examples of the “Ci-ioalkylene” include, for example, methylene, ethylene, propylene, 1-methylethylene, butylene, 2-methylpropylene, 1-methylpropylene, 1 , 1-dimethylethylene, pentylene, 3-methylbutylene,
• a "C 2 -ioalkenylene” means a linear or branched, unsaturated hydrocarbon having two to ten carbon atoms and containing one to five double bonds.
• the "C 2 -ioalkenylene” includes, preferably, “C 2 -6 alkenylene” .
• Specific examples of the “C 2 -ioalkenylene” include, for example, vinylene, propenylene, methylpropenylene, butenylene, methylbutenylene, pentenylene, hexenylene, heptenylene, octenylene, nonenylene, decenylene, and the like.
• a "C 2 -ioalkynylene” means a linear or branched, unsaturated hydrocarbon having two to ten carbon atoms and containing one triple bond.
• the "C 2 -ioalkynylene” includes, preferably, “C 2 -6 alkynylene” .
• Specific examples of the “C 2 -ioalkynylene” include, for example, propynylene, methylpropynylene, butynylene, methylbutynylene, pentynylene, hexynylene, heptynylene, octynylene, nonynylene, decynylene, and the like.
• a “C3-iocycloalkyl group” means a cyclic alkyl having three to ten carbon atoms, and includes those cyclic alkyl having a partially bridged structure.
• the "C3-iocycloalkyl group” includes, preferably a "C3 - 7 cycloalkyl group", and more preferably a "C4 - 6 cycloalkyl group”.
• C3-iocycloalkyl group examples include, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, a cyclooctyl group, an adamantyl group, and the like.
• Specific examples of the "C3 - 7 cycloalkyl group” include, for example, a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, and the like.
• C3-iocycloalkyl group encompasses those compounds in which it is fused to an aromatic ring. Specific examples thereof include, for example, groups represented by the following and the like.
• C3-iocycloalkyl group also encompasses a saturated bicyclo ring. Specific examples thereof include, for example, groups represented by the following group and the like.
• C3-iocycloalkylcarbonyl group the "C3-iocycloalkylthio group”
• C3-iocycloalkylsulfinyl group the "C3-iocycloalkylsulfonyl group” is defined the same as the above-described "C3-iocycloalkyl group”.
• C3-iocycloalkylcarbonyl group examples include, preferably, those groups in which the "C3-iocycloalkyl” moiety is the "C3 - 7 cycloalkyl group”.
• Specific examples of the "C3-iocycloalkylcarbonyl group” include, for example, a cyclopropylcarbonyl group and the like.
• C3-iocycloalkylthio group examples include, for example, a cyclopropylthio group and the like.
• Specific examples of the "C3-iocycloalkylsulfinyl group” include, for example, a cyclopropylsulfinyl group and the like.
• Specific examples of the "C3-iocycloalkylsulfonyl group” include, for example, a cyclopropylsulfonyl group and the like.
• a "C3-iocycloalkylene” means a cyclic alkylene having three to ten carbon atoms, and encompasses those cycloalkylene having a partially bridged structure.
• the "C3-iocycloalkylene” includes, preferably, "C4 - 7 cycloalkylene” . Specific examples of the
• C3-iocycloalkylene include, for example, cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene, cycloheptylene, cyclooctylene, adamantylene, and the like.
• Specific examples of the "C4 - 7 cycloalkylene” include, for example, cyclobutylene, cyclopentylene, cyclohexylene, cycloheptylene, and the like.
• C 3 -iocycloalkylene and “C4 - 7 cycloalkylene” encompass those compounds in which it is fused to an aromatic ring. Specific examples thereof include, for example, groups represented by the following and the like.
• C 3 -iocycloalkylene and “C4 - 7 cycloalkylene” encompass a saturated bicyclo ring. Specific examples thereof include, for example, groups represented by the following group and the like.
• Ci-6alkoxy group refers to a “Ci-6alkyloxy group", and the "Ci-6alkyl” moiety is defined the same as the above-described "Ci-6alkyl group”.
• the "Ci-6alkoxy group” includes, preferably, a "Ci- 4 alkoxy group” and the like.
• Ci- 6 alkoxy group examples include, for example, a methoxy group, an ethoxy group, a propoxy group, a 1-methylethoxy group, a butoxy group, a 2-methylpropoxy group, a 1-methylpropoxy group, a 1 , 1-dimethylethoxy group, a pentyloxy group, a 3-methylbutoxy group, a 2-methylbutoxy group, a 2 , 2-dimethylpropoxy group, a 1-ethylpropoxy group, a 1 , 1-dimethylpropoxy group, a hexyloxy group, a 4-methylpentyloxy group, a 3-methylpentyloxy group, a 2-methylpentyloxy group, a 1-methylpentyloxy group, a 3 , 3-dimethylbutoxy group, a 2 , 2-dimethylbutoxy group, a 1 , 1-dimethylbutoxy group, a 1 , 2-dimethylbutoxy group, and the like
• C3-iocycloalkoxy group refers to a "C3-iocycloalkyloxy group", and the "C3-iocycloalkyl” moiety is defined the same as the above-described "C3-iocycloalkyl group”.
• the "C 3 -i 0 cycloalkoxy group” includes, preferably, a "C3 - 7 cycloalkoxy group”.
• C3-iocycloalkyloxy group examples include, for example, a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexyloxy group, a cycloheptyloxy group, a cyclooctyloxy group, an adamantyloxy group, and the like.
• Specific examples of the "C3 - 7 cycloalkoxy group” include, for example, a cyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a cyclohexyloxy group, a cycloheptyloxy group, and the like.
• the "C 3 -i 0 cycloalkoxy" moiety of the "C3-iocycloalkoxycarbonyl group” are defined the same as the above-described "C3-iocycloalkoxy group".
• the "C3-iocycloalkoxycarbonyl group” includes, preferably, a "C3 - 7 cycloalkoxycarbonyl group”. Specific examples of the "C3-iocycloalkoxycarbonyl group” include a cyclopropoxycarbonyl group and the like.
• the "Ci- 6 alkoxy”moiety of the "Ci- 6 alkoxycarbonyl group” is defined the same as the above-described "Ci- 6 alkoxy group”.
• the "Ci-6alkoxycarbonyl group” includes, preferably, a "Ci - 4 alkoxycarbonyl group”. Specific examples of the "Ci-6alkoxycarbonyl group” include, for example, a methoxycarbonyl group, an ethoxycarbonyl group, and the like .

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