Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
  • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
  • C07D471/04—Ortho-condensed systems
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P19/00—Drugs for skeletal disorders
  • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
  • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
  • C07D498/04—Ortho-condensed systems
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
  • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
  • C07D513/04—Ortho-condensed systems

Definitions

• the present invention relates to a novel heterocyclic compound having an EP4 receptor antagonistic action, and may be useful an agent for the prophylaxis or treatment of EP4 receptor associated diseases (e.g., rheumatoid arthritis,
• aortic aneurysm thoracoabdominal aortic aneurysm etc.
• endometriosis ankylosing spondylitis
• inflammatory breast cancer etc.
• Prostaglandin- E2 is one of the most broadly distributed prostanoids throughout animal species and widely produced within the body by the actions of cyclooxygenases (COX) on arachidonic acid. PGE2 is involved in a number of 0 physiological and pathophysiological responses such as fever, pain, inflammation (non-patent document 1) and elicits its biological functions through four- receptor subtypes EP1-4, all G-protein-coupled receptor.
• EP4 receptor activation stimulates dendritic cells and promotes IL-23 production synergistically with CD40 and Toll-like receptor signaling.
• PGE2 then . enhances the expansion 0 of Thl7 cells with IL-23.
• EP4 receptor activation promotes the differentiation of Thl from naive T cells synergistically with IL-12.
• PGE2 synergistically induces IL-6 and IL- ⁇ expression with LPS via EP4 receptors in macrophages.
• Thl, Thl7 and macrophage cells play key roles in the development of
• Non-steroidal anti-inflammatory drugs and COX-2 inhibitors are clinically proven to relieve inflammation and pain by inhibiting the synthesis of arachidonic acid pathway metabolites including PGE2.
• NSAIDs non-steroidal anti-inflammatory drugs
• COX-2 inhibitors are clinically proven to relieve inflammation and pain by inhibiting the synthesis of arachidonic acid pathway metabolites including PGE2.
• their use is associated with adverse effects due to pleiotropic function of
• aortic aneurysm e.g. abdominal aortic aneurysm, thoracic aortic aneurysm, thoracoabdominal aortic aneurysm etc.
• aortic aneurysm e.g. abdominal aortic aneurysm, thoracic aortic aneurysm, thoracoabdominal aortic aneurysm etc.
• Endometriosis is a chronic, estrogen- dependent inflammatory disease and defined as the presence of functional endometrial tissue at ectopic sites. It is a common disease that 10-20% of women of reproductive age are affected. The most common symptom is a dysmenorrhea. Chronic pelvic pain, dyspareunia, dyschezia (pain on defecation), loin pain, lower abdominal pain or back pain, pain on micturition, pain on exercise are also part of the symptoms of EM (non-patent
• AAA Abdominal aortic aneurysm
• non-patent documents 18-20 characterized by localized connective tissue degeneration and smooth muscle cell apoptosis, leading to aortic dilatation and rupture. After rupture occurs, the probability of mortality is greater than 60% (non-patent document 21) . No pharmacotherapy has been found to be
• COX-2 is widely expressed in macrophages and smooth muscle cells, along with locally synthetized PGE2 (non-patent document 22) .
• EP4 expression is increased in the aneurysm areas of human AAA tissues, both in human aortic aneurysm smooth muscle cell as well as in
• EP4 receptor antagonist or global gene deletion of the EP4 receptor significantly decreased MMP-2 activation and IL-6 production in human AAA tissues and the rate of AAA formation in preclinical mouse models (non-patent document 23 and 25) .
• Ankylosing spondylitis is the prototypic
• spondyloarthropathy one of a group of conditions which also includes psoriatic arthritis, reactive arthritis and arthritis complicating inflammatory bowel disease.
• spondylitis is highly heritable (non-patent documents 26 and 27) and familial (non-patent document 28) . Men are affected 2- 3 times more frequently than women. The disease is known to be strongly associated with HLA-B27. Since association between EP4 receptor ⁇ gene (PTGER4) and ankylosing spondylitis has been also demonstrated (non-patent document 29) , EP4 receptor is likely to be involved in disease pathogenesis. There is no cure for ankylosing spondylitis as yet, but the patient's back pain and stiffness usually show good symptomatic response to NSAIDs.
• PTGER4 receptor ⁇ gene PTGER4 receptor ⁇ gene
• EP4 antagonists are known to possess analgesic activity at least in animal models (non-patent documents 30 and 31), a safe and chronically-treatable EP4 antagonist may be an alternative symptom-relieving pharmacotherapy for ankylosing spondylitis.
• Examples of the compound having a structure similar to the compound described in the present specification include the following compounds.
• Patent document 1 describes a compound represented by the formula :
• each symbol is as defined in the specification, which is useful as an agent for the prophylaxis or treatment of metabolic disease, cerebrovascular disease and the like.
• each symbol is as defined in the specification, as a corticotropin releasing factor (CRF) , which is useful as an agent for the prophylaxis or treatment of anxiety,
• Patent document 5 describes a .compound represented by the formula:
• Patent Document 3 WO 97/44038 Al
• Non-Patent Document 1 Pharmacol. Rev., 2011. 63(3): p. 471 15 538
• Non-Patent Document 2 Trends Pharmacol. Sci., 2012. 33(6) 304-11
• Non-Patent Document 5 Immunity, 2010. 33(2): p. 150-2
• Non-Patent Document 8 Br. J. Pharmacol., 2010. 160(2): p.
• Non-Patent Document 9 BMJ, 2001. 323(7304): p. 93-5
• Non-Patent Document 10 J. Pharm. Pharm. Sci., 2013. 16(5) 821-47
• Non-Patent Document 12 Mol .. Endocrinol . , 2009. 23(8): p. 1291-305
• Non-Patent Document 13 Fertil Steril, 2010. 93(8): p. 2498 35 506
• Non-Patent Document 14 Mol. Cell Endocrinol., 2011. 332(1- 2) : p. 306-13
• Non-Patent Document 15 Biol. Reprod, 2013. 88(3): p. 77
• Non-Patent Document 17 N. Engl. J. Med., 1993. 328 (16 : p. 1167-72
• Non-Patent Document 18 J. Clin. Invest,, 1998. 102(11): p. 1900-10
• Non-Patent Document 20 J. Immunol., 2004. 172 (4): " p. 2607-12
• Non-Patent Document 21 World J. Surg., 2008. 32(6): p. 976- 86
• Non-Patent Document 22 Circulation, 1999. 100(1): p. 48-54
• Non-Patent Document 23 PLoS One, 2012. 7(5): p. e36724
• Non-Patent Document 24 J. Vase. Surg., 2003. 38(2): p. 354-9
• Non-Patent Document 25 Am. J. Pathol., 2012. 181(1): p. 313- 21
• Non-Patent Document 26 Scand. J. Rheumatol . , 2008. 37: p. 120-126
• the present invention provides the following.
• G 2 is a carbon atom or a nitrogen atom
• Ring A is an optionally further substituted 6-membered
• G 3 is an oxygen atom, an optionally substituted methylene, NR 1 , a sulfur atom, S (0) or S(0) 2 ,
• Ci_4 alkylene group optionally substituted by an oxo group
• a method of inhibiting EP4 receptor in a mammal which comprises administering an effective amount of the compound or salt of the above-mentioned [1] to the mammal.
• examples of the "C 3 _i 0 cycloalkenyl group” include cyclopropenyl , cyclobutenyl , cyclopentenyl, cyclohexenyl, cycloheptenyl and cyclooctenyl.
• examples of the "optionally halogenated Ci-6 alkoxy group” include a Ci-6 alkoxy group
• alkylthio group include methylthio, ethylthio, propylthio, isopropylthio, butylthio, sec-butylthio, tert-butylthio, pentylthio and hexylthio.
• examples of the "optionally halogenated Ci-6 alkyl-carbonyl group” include a Ci- 6 alkyl- carbonyl group optionally having 1 to 7, preferably 1 to 5, halogen ' atoms. Specific examples thereof include acetyl, chloroacetyl, trifluoroacetyl, trichloroacetyl, propanoyl, butanoyl, pentanoyl and hexanoyl .
• examples of the "Ci- 6 alkoxy-carbonyl group” include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl , butoxycarbonyl,
• examples of the "C 6 -i 4 aryl- carbonyl group” include benzoyl, 1-naphthoyl and 2-naphthoyl.
• examples of the “C 7 -i 6 aralkyl-carbonyl group” include phenylacetyl and
• examples of the "5- to 14- membered aromatic heterocyclylcarbonyl group” include
• examples of the "3- to 14- membered non-aromatic heterocyclylcarbonyl group” include morpholinylcarbonyl, piperidinylcarbonyl and
• alkylsulfonyl group include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl , sec- butylsulfonyl and tert-butylsulfonyl .
• examples of the "optionally halogenated Ci-e alkylsulfonyl group” include a Ci-6 alkylsulfonyl group optionally having 1 to 7, preferably 1 to 5, halogen atoms. Specific examples thereof include
• examples of the "C6-14 arylsulfonyl group” include phenylsulfonyl , 1-naphthylsulfonyl and 2-naphthylsulfonyl .
• substituted include a halogen atom, a cyano group, a nitro group, an optionally substituted . hydrocarbon group, an
• optionally substituted heterocyclic group an acyl group, an optionally substituted amino group, an optionally substituted carbamoyl group, an optionally substituted thiocarbamoyl group, an optionally substituted sulfamoyl group, an optionally
• hydrocarbon group (including “hydrocarbon group” of
• “optionally substituted hydrocarbon group” include a Ci_ 6 alkyl group, a C 2 - 6 alkenyl group, a C 2 -6 alkynyl group, a C3-10
• cycloalkyl group a C3-10 cycloalkenyl group, a Ce-14 aryl group and a C7-16 aralkyl group.
• examples of the "optionally substituted hydrocarbon group” include a hydrocarbon group optionally having substituent (s) selected from the following substituent group A.
• a Ce-14 aryloxy group e.g., phenoxy, -naphthoxy
• Ci-6 alkyl-carbonyloxy group e.g., acetoxy
• a C6-14 aryl-carbonyloxy group e.g., benzoyloxy, 1- naphthoyloxy, 2-naphthoyloxy
• a C6-14 aryl-carbonyloxy group e.g., benzoyloxy, 1- naphthoyloxy, 2-naphthoyloxy
• Ci-6 alkoxy-carbonyloxy group e.g., methoxycarbonyloxy, ethoxycarbonyloxy, propoxycarbonyloxy, butoxycarbonyloxy
• a mono- or di-Ci_ 6 alkyl-carbamoyloxy group e.g.,
• a Ce-14 aryl-carbamoyloxy group e.g., phenylcarbamoyloxy, naphthylcarbamoyloxy
• a 5- to 14-membered aromatic heterocyclylcarbonyloxy group e.g., nicotinoyloxy
• a 3- to 14-membered non-aromatic heterocyclylcarbonyloxy group e.g., morpholinylcarbonyloxy, piperidinylcarbonyloxy
• Ci_ 6 alkylsulfonyloxy group e.g., methylsulfonyloxy, trifluoromethylsulfonyloxy
• a C6-14 aryloxy-carbonyl group e.g., phenyloxycarbonyl, 1- naphthyloxycarbonyl, 2-naphthyloxycarbonyl ) ,
• a C 7 -i6 aralkyloxy-carbonyl group e.g., benzyloxycarbonyl , phenethyloxycarbonyl
• a C 6 -i4 aryl-carbamoyl group e.g., phenylcarbamoyl
• a 5- to 14-membered aromatic heterocyclylcarbamoyl group e.g., pyridylcarbamoyl, thienylcarbamoyl
• a 5- to 14-membered aromatic heterocyclylsulfonyl group e.g., pyridylsulfonyl, thienylsulfonyl ) , .
• a C6-14 arylsulfinyl group e.g., phenylsulfinyl , 1- naphthylsulfinyl, 2-naphthylsulfinyl ) ,
• a 5- to 14-membered aromatic heterocyclylsulfinyl group e.g., pyridylsulfinyl, thienylsulfinyl
• a mono- or di-Ci_6 alkylamino group e.g., methylamino, ethylamino, propylamino, isopropylamino, butylamino,
• a mono- or di-C 6 -i4 arylamino group e.g., phenylamino
• Ci-6 alkyl-carbonylamino group e.g., acetylamino, propanoylamino, butanoylamino
• a (Ci-6 alkyl) (Ci- 6 alkyl-carbo yl) amino group e.g., N- acetyl-N-methylamino
• a C 6 -i4 aryl-carbonylamino group e.g., phenylcarbonylamino, naphthylcarbonylamino
• Ci-6 alkoxy-carbonylamino group e.g.,
• Ci-6 alkylsulfonylamino group e.g., methylsulfonylamino, e.thylsulfonylamino
• a Ci-6 alkylsulfonylamino group e.g., methylsulfonylamino, e.thylsulfonylamino
• a C6-1 arylsulfonylamino group optionally substituted by a Ci-6 alkyl group e.g., phenylsulfonylamino
• the number of the above-mentioned substituents in the "optionally substituted hydrocarbon group” is, for example, 1 to 5, preferably 1 to 3.. When the number of the substituents is two or more, the respective substituents may be the same or different .
• heterocyclic group (including “heterocyclic group” of
• optionally substituted heterocyclic group include (i) an aromatic heterocyclic group, (ii) a non-aromatic heterocyclic group and (iii) a 7- to 10-membered bridged heterocyclic group, each containing, as a ring-constituting atom besides carbon atom, 1 to 4 hetero atoms selected from a nitrogen atom, a sulfur atom and an oxygen atom.
• examples of the "aromatic heterocyclic group” include a 5- to 14-membered (preferably 5- to 10-membered) aromatic heterocyclic group containing, as a ring-constituting atom besides carbon atom, 1 to 4 hetero atoms selected from a nitrogen atom, a sulfur atom and an oxygen atom.
• aromatic heterocyclic group examples include 5- or 6-membered monocyclic aromatic heterocyclic groups such as thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl , oxazolyl, isoxazolyl, pyridyl,
• pyrazinyl pyrimidinyl, pyridazinyl, 1, 2, -oxadiazolyl, 1,3,4- oxadiazolyl, 1, 2, 4-thiadiazolyl, 1, 3, -thiadiazolyl, triazolyl, tetrazolyl, triazinyl and the like;
• benzothiophenyl benzofuranyl, benzimidazolyl, benzoxazolyl, benzisoxazolyl, benzothiazolyl, benzisothiazolyl ,
• furopyridinyl pyrrolopyridinyl , pyrazolopyridinyl ,
• quinoxalinyl quinazolinyl, cinnolinyl, carbazolyl, ⁇ - carbolinyl, phenanthridinyl, acridinyl, phenazinyl,
• non-aromatic heterocyclic group examples include 3- to 8-membered monocyclic non-aromatic heterocyclic groups such as aziridinyl, oxiranyl, thiiranyl, azetidinyl, oxetanyl, thietanyl, tetrahydrothienyl ,
• examples of the "acyl group” include a formyl group, a carboxy group, a carbamoyl group, a thiocarbamoyl group, a sulfino group, a sulfo group, a sulfamoyl group and a phosphono group, each optionally having "1 or 2 substituents selected from a Ci-6 alkyl group, a C2-6 alkenyl group, a C3-10 cycloalkyl group, a C3-10 cycloalkenyl group, a C 6 -i4 aryl group, a C7-16 aralkyl group, a 5- to 14- membered aromatic heterocyclic group and a .3- to 14-membered non-aromatic heterocyclic group, each of which optionally has 1 to 3 substituents selected from a halogen atom, an
• heterocyclylthiocarbamoyl group e.g., pyridylthiocarbamoyl
• a sulfino group e.g., a sulfino group
• a Ci_ 6 alkylsulfinyl group e.g.,
• examples of the "optionally substituted carbamoyl group” include a carbamoyl group
• 35 14-membered aromatic heterocyclylcarbamoyl group (e.g., pyridylcarbamoyl) .
• heterocyclylcarbonyloxy group e.g., nicotinoyloxy
• a 3- to 14-membered non-aromatic heterocyclylcarbonyloxy group e.g., piperidinylcarbonyloxy
• a Ci_ 6 alkoxy-carbonyloxy group e.g., tert-butoxycarbonyloxy
• examples of the "C 3 -io cycloalkene” include cyclopropene, cyclobutene, cyclopentene, cyclohexene, cycloheptene and cyclooctene.
• heterocycle examples include an aromatic heterocycle and a non- aromatic heterocycle, each containing, as a ring-constituting atom besides carbon atom, 1 to 4 hetero atoms selected from a nitrogen atom, a sulfur atom and an oxygen atom.
• aromatic heterocycies such as benzothiophene, benzofuran, benzimidazole, benzoxazole, benzisoxazole,
• benzothiazole benzisothiazole, benzotriazole, imidazopyridine, thienopyridine, furopyridine, pyrrolopyridine,
• imidazopyrazine imidazopyrimidine
• thienopyrimidine imidazopyrimidine
• furopyrimidine furopyrimidine, pyrrolopyrimidine , pyrazolopyrimidine,
• quinazoline quinazoline, cinnoline, carbazole, ⁇ -carboline, phenanthridine, acridine, phenazine, phenothiazine, phenoxazine and the like.
• tricyclic non-aromatic heterocycles such as dihydrobenzofuran, dihydrobenzimidazole, dihydrobenzoxazole, dihydrobenzothiazole, dihydrobenzisothiazole, dihydronaphtho [2 , 3-b] thiophene,
• examples of the "nitrogen- containing heterocycle” include a “heterocycle” containing at least one nitrogen atom as a ring-constituting, atom.
• G 1 is a carbon atom or a nitrogen atom.
• G 1 is preferably a carbon atom.
• G 2 is a carbon atom or a nitrogen atom.
• G 2 is preferably a carbon atom.
• Ring A is an optionally further substituted 5-membered nitrogen-containing heterocycle.
• the "6-membered nitrogen-containing heterocycle" of the "optionally further substituted 6-membered nitrogen-containing heterocycle" for Ring A is preferably pyridine or pyrimidine, more preferably pyridine.
• the "6-membered nitrogen-containing heterocycle" of the "optionally further substituted 6-membered nitrogen-containing heterocycle" for Ring A optionally has 1 or 2 substituents at substitutable position(s), in addition to -N (R 4 ) -C (R 1 ) (R 2 ) -Ring B ' .
• substituents include substituents selected from the aforementioned substituent group A. When the number of the substituents is plural, the respective substituents may be the same or different.
• Ring A is preferably an optionally further substituted pyridine .
• Ring A is preferably an optionally further substituted pyridine or an optionally further
• Ring A is more preferably pyridine or pyrimidine, each of which is optionally further substituted by 1 to 2 substituents selected from the group consisting of
• a halogen atom e.g., a chlorine atom
• Ci-6 alkyl group e.g., methyl
• a C3-10 cycloalkyl group e.g., cyclopropyl
• Ring A is still more preferably
• a halogen atom e.g., a chlorine atom
• Ci-6 alkyl group e.g. , ' methyl
• Ring A is particularly preferably pyridine.
• G 3 is an oxygen atom, an optionally substituted methylene, NR 1 , a sulfur atom, S (0) or S(0) 2 .
• R 1 is a hydrogen atom or a substituent.
• the "methylene” of the “optionally substituted methylene” for G 3 optionally has 1 or 2 substituents at substitutable position(s).
• substituents include substituents selected from the aforementioned substituent group A. When the number of the substituents is plural, the respective
• G 3 is preferably an oxygen atom or NR 1 wherein R 1 is as defined above.
• G 3 is more preferably an oxygen atom or NR 1 wherein R 1 is a Ci-6 alkyl group (e.g., methyl).
• G 3 is preferably an oxygen atom, an optionally substituted methylene, NR 1 wherein R 1 is as defined above, or a sulfur atom.
• G 3 is more preferably an oxygen atom, NR 1 wherein R 1 is a Ci- 6 alkyl group (e.g., methyl), methylene or a sulfur atom.
• G 3 is particularly an oxygen atom.
• X is an optionally substituted ethylene.
• the "ethylene” of the "optionally substituted ethylene” for X optionally has 1 to 4 substituents at ⁇ substitutable position (s).
• substituents include substituents selected from the aforementioned substituent group A. When the number of the substituents is plural, the respective
• X is preferably ethylene.
• X is preferably ethylene - optionally substituted by an oxo group.
• X is particularly preferably ethylene.
• R 2 and R 3 are each independently a hydrogen atom or an optionally substituted Ci-6 alkyl group, or R 2 and R 3 are joined together to form a cycloalkane or a heterocycle, each of which is optionally substituted.
• Ci-6 alkyl group of the "optionally substituted Ci_ 6 alkyl group” optionally has 1 to 5 substituents (preferably 1 to 3) at substitutable position (s). Examples of the
• substituents include substituents selected from the
• Examples of the "cycloalkane” of the “cycloalkane or heterocycle, each of which is optionally substituted” formed by R 1 and R 2 include a C 3 -i 0 cycloalkane (preferably a C3-6
• the "cycloalkane or heterocycle" of the “cycloalkane or heterocycle, each of which is optionally substituted” formed by R 2 and R 3 has 1 to 5 substituents (preferably 1 to 3) at substitutable position (s).
• substituents include substituents selected from the aforementioned substituent group A. When the number of the substituents is plural, the respective substituents may be the same or different.
• R 2 and R 3 are each a hydrogen atom or an optionally substituted Ci- 6 alkyl group (e.g., methyl), or R 2 and R 3 are joined together to form an optionally substituted cycloalkane (preferably a C3-10 cycloalkane, more preferably a C3-6 cycloalkane (e.g., cyclopropane)).
• an optionally substituted cycloalkane preferably a C3-10 cycloalkane, more preferably a C3-6 cycloalkane (e.g., cyclopropane)).
• R 2 and R 3 are each a hydrogen atom or a C1-6 alkyl group (e.g., methyl), or R 2 and R 3 are joined
• cycloalkane e.g., cyclopropane
• R 2 is a Ci-6 alkyl group (e.g., methyl), and R 3 is a hydrogen atom, or R 2 and R 3 are joined together to form a C3-10 cycloalkane (preferably a C3-6
• cycloalkane e.g., cyclopropane
• R 2 is a hydrogen atom or a Ci- 6 alkyl group (e.g., methyl), and R 3 is a hydrogen atom, or R 2 and R 3 are joined together to form a C3-10 cycloalkane (preferably a C 3 -. 6 cycloalkane (e.g., cyclopropane)).
• a C3-10 cycloalkane preferably a C 3 -. 6 cycloalkane (e.g., cyclopropane)
• R 2 is a Ci_ 6 alkyl group (e.g., methyl), and R 3 is a hydrogen atom, or R 2 and R 3 are joined together to form a C 3 -6 cycloalkane (e.g., cyclopropane).
• R 4 is a hydrogen atom or a substituent.
• R 4 is preferably a hydrogen atom.
• Ring B is an optionally further substituted ring.
• substituted ring" for Ring B include a hydrocarbon ring and a heterocycle (preferably a C6-1 aromatic hydrocarbon ring
• the "ring" of the “optionally further substituted ring” for Ring B optionally has 1 to 5 (preferably 1 to 3)
• substituents at substitutable position (s), in addition to - CfR 1 ) (R 2 ) -N (R 4 ) -Ring A examples include an optionally further substituted pyridine substituents selected from the aforementioned substituent group A. When the number of the substituents is plural, the respective substituents may be the same or different.
• Ring B is preferably an optionally further substituted C6-14 aromatic hydrocarbon ring (preferably benzene) .
• Ring B is more preferably a C 6 -i4 aromatic hydrocarbon ring (preferably benzene) optionally further substituted by 1 to 3 (preferably one) substituents selected from the group consisting of
• Ci-6 alkoxy-carbonyl group e.g., methoxycarbonyl
• a mono- or di-C 7 _i S aralkyloxy-carbamoyl group e.g., benzyloxycarbamoyl
• Ring B is still more preferably benzene optionally further substituted by 1 to 3 (preferably one) substituents selected from the group consisting of
• Ci-6 alkoxy-carbonyl group e.g., methoxycarbonyl
• Ring B is preferably an optionally further substituted C 6 -i 4 aromatic hydrocarbon ring (preferably a C6-io aromatic hydrocarbon ring, more preferably benzene) , an optionally further substituted C3-10 cycloalkane (preferably a C3-6 cycloalkane, more preferably cyclohexane) or an optionally further substituted 5- to 10-membered aromatic heterocycle
• Ring B is more preferably
• aromatic hydrocarbon ring more preferably benzene
• aromatic hydrocarbon ring more preferably benzene
• 1 to 3 preferably one
• Ci-6 alkoxy-carbonyl group e.g., methoxycarbonyl
• a mono- or di-C 7 _i6 aralkyloxy-carbamoyl group e.g., benzyloxycarbamoyl
• Ci-6 alkoxy group e.g., methoxy
• a 5- to 10-membered aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine
• 1 to 3 preferably one
• Ci-6 alkyl groups e.g., methyl
• Ring B is still more preferably
• Ci-6 alkoxy-carbonyl group e.g., methoxycarbonyl
• Ci-6 alkoxy group e.g., methoxy
• Ci- 6 alkyl groups e.g., methyl
• Ring B is particularly preferably benzene further substituted by one carboxy group.
• Ring C is an optionally further substituted ring.
• Ring C examples include a hydrocarbon ring and a heterocycle (preferably a C 6 -i4 aromatic hydrocarbon ring
• a C6-10 aromatic hydrocarbon ring preferably benzene, naphthalene
• a C3-10 cycloalkane preferably a C3-6 cycloalkane, more preferably cyclohexane
• a 5- to 14- membered preferably 5- to 10-membered
• aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine, furan, isoxazole
• a C 6 -io aromatic hydrocarbon ring preferably benzene
• naphthalene a C 3 - 6 cycloalkane (preferably cyclohexane) or a
• 5- or 6-membered monocyclic aromatic heterocycle preferably pyridine, furan, isoxazole
• the "ring” of the “optionally further substituted ring” for Ring C optionally has 1 to 5 (preferably 1 to 3)
• substituents at substitutable position(s), in addition to -W- examples include substituents selected from the aforementioned substituent group A. When the number of the substituents is plural, the respective substituents may be the same or different.
• Ring C is preferably a C6-14 aromatic hydrocarbon ring (preferably benzene, naphthalene) or a 5- to 14-membered
• Ring C is more preferably a Ce-i4 aromatic hydrocarbon ring (preferably benzene, naphthalene) or a 5- to 14-membered (preferably 5- to 10-membered) aromatic heterocycle
• hydrocarbon ring preferably benzene, naphthalene
• 5- or 6-membered monocyclic aromatic heterocycle preferably
• a halogen atom e.g., a fluorine atom, a -chlorine atom
• Ci_ 6 alkyl group e.g., methyl, trifluoromethyl
• Ci- 6 alkoxy group e.g., methoxy
• Ring C is still more preferably benzene, naphthalene, pyridine or furan, each of which is optionally further
• a halogen atom e.g., a fluorine atom, a chlorine atom
• Ci_ 6 alkyl group e.g., methyl, trifluoromethyl
• Ci-6 alkoxy group e.g., methoxy
• Ring C is preferably a Ce-u
• aromatic hydrocarbon ring preferably a C 6 -io aromatic
• hydrocarbon ring more preferably benzene, naphthalene
• a C 3 - 10 cycloalkane preferably a C3-6 cycloalkane, more preferably cyclohexane
• a 5- to 14-membered (preferably 5- to 10- membered) aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine, furan, isoxazole
• a C 6 -io aromatic hydrocarbon ring preferably benzene, naphthalene
• Ring C is more preferably a C 6 -i4
• aromatic hydrocarbon ring preferably a C 6 _io aromatic
• hydrocarbon ring more preferably benzene, naphthalene
• a C3-10 cycloalkane preferably a C 3 - 6 cycloalkane, more preferably cyclohexane
• a 5- to 14-membered (preferably 5- to 10- membered) aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine, furan, isoxazole
• a C 6 -io aromatic hydrocarbon ring preferably benzene, naphthalene
• a halogen, atom e.g., a fluorine atom, a chlorine atom
• an optionally halogenated Ci- 6 alkyl group e.g., methyl, trifluoromethyl
• a Ce-1 aryl group e.g., phenyl
• Ring C is further more preferably benzene, naphthalene, cyclohexane, pyridine, furan or
• isoxazole each of which is optionally further substituted by 1 to 3 (preferably 1 or 2) substituents selected from the group consisting of
• a halogen atom e.g., a fluorine atom, a chlorine atom
• Ci- 6 alkyl group e.g., methyl, trifluoromethyl
• Ci- 6 alkoxy group e.g., methoxy
• Ring C is still more preferably benzene further substituted, by 1 or 2 substituents selected ⁇ from the group consisting of
• halogen atom e.g., a fluorine atom, a chlorine atom
• ⁇ halogen atom e.g., a fluorine atom, a chlorine atom
• Ci-6 alkoxy group e.g., methoxy
• Ring C is particularly preferably benzene further substituted by 1 or 2 halogen atoms (e.g., a fluorine atom, a chlorine atom) .
• W is a bond, or a spacer in which the number of atoms in the main chain is 1 to 4.
• Examples of the "spacer in which the number of atoms in the main chain is 1 to 4" for include spacers wherein the main. chain consists of 1 to 4 atoms selected from a carbon atom, a nitrogen atom, a sulfur atom (optionally oxidized) and an oxygen atom, each of which optionally has substituent ( s ) selected from the aforementioned substituent group A at substitutable position (s).
• Ci-4 alkylene group e.g., -CH 2 -, -(CH 2 ) 2 - / -CH 2 -CH (CH 3 ) -, -CH (CH 3 ) -CH 2 -, -(CH 2 ) 3 -, -(CH 2 ) 4 - etc.
• substituent group A preferably a halogen atom (e.g., a fluorine atom, a chlorine atom), an oxo group and a hydroxy group
• halogen atom e.g., a fluorine atom, a chlorine atom
• Z 1 and Z 2 are each independently 0, C(0), NR 6 (R 6 is a hydrogen atom or a substituent), S, S (0) or
• a C 3 -6 cycloalkylene e.g., cyclopropylene, cyclobutylene, cyclopentylene, cyclohexylene etc.
• a divalent non-aromatic heterocyclic group e.g., 1,2- aziridinediyl, 1, 3-azetidinediyl, 1, 3-pyrrolidinediyl, 1,3- piperidinediyl, 1, 4-piperidinediyl, 1, -morpholinediyl etc.
• Y is a divalent non-aromatic heterocyclic group (e.g., 1,2- aziridinediyl, 1 , 3-azetidinediyl, 1 , 3-pyrrolidinediyl , 1,3- piperidinediyl etc.);
• W is preferably a spacer in which the number of atoms in the main chain is 1 to 4.
• W is more preferably
• Ci-4 alkylene group e.g., -CH 2 ⁇
• a Ci-4 alkylene group e.g., -CH 2 ⁇
• W is still more preferably -CH 2 - or -CH 2 CH 2 0- (wherein the left bond is bonded to the nitrogen atom, and the right bond is bonded to Ring C) .
• W is more preferably
• Ci-4 alkylene group e.g., -CH 2 -, -(CH 2 ) 2 -
• oxo group optionally substituted by an oxo group
• is still more preferably -CH 2 -, - (CH 2 ) 2 -, -CH 2 CH 2 0- (wherein the left bond is bonded to the nitrogen atom, and the right bond is bonded to Ring C) or - C( 0)-.
• compound (I) include the following compounds .
• G 1 is a carbon atom or a nitrogen atom
• G 2 is a carbon atom or a nitrogen atom
• Ring A is an optionally further substituted pyridine
• G 3 is an oxygen atom or NR 1 wherein R 1 is as defined above, X is an optionally substituted ethylene,
• R 2 and R 3 are each a hydrogen atom or an optionally substituted Ci-6 alkyl group (e.g., methyl), or R 2 and R 3 are joined together to form an optionally substituted cycloalkane (preferably a C3-10 cycloalkane, more preferably a C3-6
• cycloalkane e.g., cyclopropane
• R 4 is a hydrogen atom
• Ring B is an optionally further C 6 -i4 aromatic hydrocarbon ring (preferably benzene) ,
• Ring C is a C 6 -i4 aromatic hydrocarbon ring (preferably benzene, naphthalene) or a 5- to 14-membered (preferably 5- to 10-membered) aromatic heterocycle (preferably pyridine, furan) (preferably a C 6 -i4 aromatic hydrocarbon ring (preferably benzene, naphthalene) or a 5- or 6-membered monocyclic
• aromatic heterocycle preferably pyridine, furan
• W is a spacer in which the number of atoms in the main chain is 1 to 4.
• G 1 is a carbon atom
• G 2 is a carbon atom
• Ring A is pyridine optionally further substituted by 1 to
• halogen atoms e.g., a chlorine atom
• G 3 is an oxygen atom or NR 1 wherein R 1 is a Ci-6 alkyl group (e.g. , ' methyl) ,
• X is ethylene
• R 2 and R 3 are each a hydrogen atom or a Ci_ 6 alkyl group (e.g., methyl), or R 2 and R 3 are joined together to form a C3-10 cycloalkane (preferably a C3-6 cycloalkane (e.g., cyclopropane)), R 4 is a hydrogen atom,
• Ring B is a Ce-14 aromatic hydrocarbon ring (preferably benzene) optionally further substituted by .1 to 3 (preferably one) substituents selected from the group consisting of
• Ci-6 alkoxy-carbonyl group e . g . , . methoxycarbonyl
• Ring C is a C6-14 aromatic hydrocarbon ring (preferably benzene, naphthalene) or a 5- to 14-membered (preferably 5- to 10-membered) aromatic heterocycle (preferably pyridine, furan) (preferably a Ce-u aromatic hydrocarbon ring (preferably
• aromatic heterocycle preferably pyridine, furan
• 1 to 3 preferably 1 or 2 substituents selected from the group consisting of
• a halogen atom e.g., a fluorine atom, a chlorine atom
• Ci-6 alkyl group e.g., methyl, trifluoromethyl
• Ci-6 alkoxy group e.g., methoxy
• G 1 is a carbon atom
• G 2 is a carbon atom
• Ring A is pyridine optionally further substituted by 1 to
• halogen atoms e.g., a chlorine atom
• G 3 is an oxygen atom or NR 1 wherein R 1 is a Ci- 6 alkyl group (e.g., methyl),
• X is ethylene
• R 2 is a Ci-6 alkyl group (e.g., methyl), and R 3 is a hydrogen atom, or R 2 and R 3 are joined together to form a C3-10 cycloalkane (preferably a C3-6 cycloalkane (e.g., cyclopropane)), R 4 is a hydrogen atom,
• Ci-6 alkoxy-carbonyl group e.g., methoxycarbonyl
• Ring C is benzene, naphthalene, pyridine or furan, each of which is optionally further substituted by 1 to 3
• a halogen atom e.g., a fluorine atom, a chlorine atom
• Ci-e alkyl group e.g., methyl, trifluoromethyl
• Ci-6 alkoxy group e.g., methoxy
• W is -CH 2 - or -CH 2 CH 2 0- (wherein the left bond is bonded to the nitrogen atom, and the right bond is bonded to Ring C) .
• G 1 is a carbon atom or a nitrogen atom
• G 2 is a carbon atom or a nitrogen atom
• Ring A is an optionally further substituted pyridine or an optionally further substituted pyrimidine
• G 3 is an oxygen atom, an optionally substituted methylene,
• X is an optionally substituted ethylene
• R 2 and R 3 are each a hydrogen atom or an optionally substituted Ci-6 alkyl group (e.g., methyl), or R 2 and R 3 are joined together to form an optionally substituted cycloalkane (preferably a C3-10 cycloalkane, more preferably a C3-6
• cycloalkane e.g., cyclopropane
• R 4 is a hydrogen atom
• Ring B is an optionally further substituted C 6 -i4 aromatic hydrocarbon ring (preferably a C 6 -io aromatic hydrocarbon ring, more preferably benzene) , an optionally further substituted C 3 _ 10 cycloalkane (preferably a C 3 - 6 cycloalkane, more preferably cyclohexane) or an optionally further substituted 5- to 10- membered aromatic heterocycle (preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine),
• Ring C is a C6-14 aromatic hydrocarbon ring (preferably a Ce-io aromatic hydrocarbon ring, more preferably benzene,
• naphthalene a C 3 _i 0 cycloalkane (preferably a C 3 - 6 cycloalkane, more preferably cyclohexane) or a 5- to 14-membered
• aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine, furan, isoxazole
• aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine, furan, isoxazole
• C 6 _i 0 aromatic hydrocarbon ring preferably benzene, naphthalene
• C 3 -6 cycloalkane preferably cyclohexane
• 5- or 6-membered monocyclic aromatic heterocycle preferably pyridine, furan, isoxazole
• W is a spacer in which the number of atoms in the main chain is 1 to 4.
• G 1 is a carbon atom.
• G 2 is a carbon atom or a nitrogen atom
• Ring A is pyridine or pyrimidine, each of which is
• a halogen atom e.g., a chlorine atom
• Ci-6 alkyl group e.g., methyl
• G 3 is an oxygen atom, NR 1 wherein R 1 is a Ci- 6 alkyl group (e.g., methyl), methylene or a sulfur atom,
• X is ethylene optionally substituted by an oxo group
• R 2 and R 3 are each a hydrogen atom or a C3.-6 alkyl group (e.g., methyl), or R 2 and R 3 are joined together to form a C3-10 cycloalkane (preferably a C 3 - 6 cycloalkane (e.g., cyclopropane)), R 4 is a hydrogen atom,
• aromatic hydrocarbon ring more preferably benzene
• aromatic hydrocarbon ring more preferably benzene
• 1 to 3 preferably one
• Ci-6 alkoxy-carbonyl group e.g., methoxycarbonyl
• a cyano group e.g., a carbamoyl group
• Ci-6 alkoxy group e.g., methoxy
• a 5- to 10-membered aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine
• 1 to 3 preferably one
• Ci-6 alkyl groups e.g., methyl
• Ring C is a C 6 -i4 aromatic hydrocarbon ring (preferably a C6-10 aromatic hydrocarbon ring, more preferably benzene,
• naphthalene a C3-10 cycloalkane (preferably a C3_ 6 cycloalkane, more preferably cyclohexane) or a 5- to 14-membered
• a 5- or 6-membered monocyclic aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine, furan, isoxazole
• a C6-10 aromatic hydrocarbon ring preferably benzene, naphthalene
• a C3-6 cycloalkane preferably cyclohexane
• a 5- or 6-membered monocyclic aromatic heterocycle preferably pyridine, furan, isoxazole
• a halogen atom e.g., a fluorine atom, a chlorine atom
• Ci-6 alkyl group e.g., methyl, trifluoromethyl
• Ci-6 alkoxy group e.g., methoxy
• Ci-4 alkylene group e.g., -CH 2 -, -(CH 2 ) 2 -
• oxo group optionally substituted by an oxo group
• G 1 is a carbon atom
• G 2 is a carbon atom or a nitrogen atom
• a halogen atom e.g., a chlorine atom
• Ci-6 alkyl group e.g., methyl
• a C3-10 cycloalkyl group e.g., cyclopropyl
• G 3 is an oxygen atom, NR. 1 wherein R 1 is a Ci-e alkyl group (e.g., methyl), methylene or a sulfur atom,
• X is ethylene optionally substituted by an oxo group
• R 2 and R 3 are each a hydrogen atom or a Ci- 6 alkyl group (e.g., methyl), or R 2 and R 3 are joined together to form a C3-10 cycloalkane (preferably a C 3 - 6 cycloalkane (e.g., cyclopropane)), R 4 is a hydrogen atom,
• aromatic hydrocarbon ring more preferably benzene
• aromatic hydrocarbon ring more preferably benzene
• 1 to 3 preferably one
• Ci-6 alkoxy-carbonyl group e.g., methoxycarbonyl
• Ci-6 alkoxy group e.g., methoxy
• a 5- to 10-membered aromatic heterocycle preferably a 5- or 6-membered monocyclic aromatic heterocycle, more preferably pyridine
• 1 to 3 preferably one
• Ci-6 alkyl groups e.g., methyl
• Ring C is a C 6 -i 4 aromatic hydrocarbon ring (preferably a
• C6-10 aromatic hydrocarbon ring more preferably benzene, naphthalene
• a C3-10 cycloalkane preferably a C3-6 cycloalkane, more preferably cyclohexane
• a 5- or 6-membered monocyclic aromatic heterocycle more preferably pyridine, furan, isoxazole preferably a C 6 _i 0 aromatic hydrocarbon ring (preferably benzene, naphthalene) , a C3-6 cycloalkane (preferably cyclohexane) or a 5- or 6-membered monocyclic aromatic heterocycle (preferably pyridine, furan, isoxazole)
• a halogen atom e.g., a fluorine atom, a chlorine atom
• Ci-6 alkyl group e.g., methyl, trifluoromethyl
• Ci-6 alkoxy group e.g., methoxy
• Ci-4 alkylene group e.g., -CH 2 -, -(CH 2 ) 2 -
• oxo group optionally substituted by an oxo group
• -(CH 2 )mi-0- optionally substituted by an oxo group
• ml is an integer of 0 to 3 (e.g., -
• G 1 is a carbon atom
• G 2 is a carbon atom or a nitrogen atom
• a halogen atom e.g., a chlorine atom
• a C3-10 cycloalkyl group e.g., cyclopropyl
• G 3 is an oxygen atom, NR 1 wherein R 1 is a Ci_ 6 alkyl group
• X is ethylene optionally substituted by an oxo group
• R 2 is a hydrogen atom or a Ci_ 6 alkyl group (e.g., methyl) and R 3 is a hydrogen atom, or R 2 and R 3 are joined together to form a C3-10 cycloalkane (preferably a C3-6 cycloalkane (e.g., cyclopropane) )
• a C3-10 cycloalkane preferably a C3-6 cycloalkane (e.g., cyclopropane)
• R 4 is a hydrogen atom
• Ci-6 alkoxy-carbonyl group e.g., methoxycarbonyl
• Ci-6 alkoxy group e.g., methoxy
• Ring C is benzene, naphthalene, cyclohexane, pyridine, furan or isoxazole, each of which is optionally further
• a halogen atom e.g., a fluorine atom, a chlorine atom
• an optionally halogenated Ci-6 alkyl group e.g., methyl, trifluoromethyl
• Ci-6 alkoxy group e.g., methoxy
• G 1 is a carbon atom
• G 2 is a carbon atom
• Ring A is pyridine
• G 3 is an oxygen atom
• X is ethylene
• R 2 is a Ci-6 alkyl group (e.g., methyl), and R 3 is a hydrogen atom, or R 2 and R 3 are joined together to form a C3-6 cycloalkane (e.g., cyclopropane),
• R 4 is a hydrogen atom
• Ring B is benzene further substituted by one carboxy group
• Ring C is benzene . -further substituted by 1 or 2
• a halogen atom e.g., a fluorine atom, a chlorine atom
• Ci-6 alkoxy group e.g., methoxy
• W is -CH 2 -.
• G 1 is a carbon atom
• G 2 is a carbon atom
• Ring A is pyridine
• G 3 is an oxygen atom
• X is ethylene
• R 2 is a Ci-6 alkyl group (e.g., methyl), and R 3 is a hydrogen atom, or R 2 and R 3 are joined together to form a C3-6 cycloalkane (e.g., cyclopropane),
• R 4 is a hydrogen atom
• Ring B is benzene further substituted by one carboxy group
• Ring C is benzene further substituted by 1 to 2 halogen atoms (e.g., a fluorine atom, a chlorine atom), and
• W is -CH2-.
• metal salts such as metal salts, an ammonium salt, salts with organic base, salts with inorganic acid, salts with organic acid, salts with basic or acidic amino acid, and the like.
• the metal salt include alkali metal salts such as sodium salt, potassium salt and the like;
• alkaline earth metal salts such as calcium salt, magnesium salt, barium salt and the like; an aluminum salt, and the like.
• the salt with organic base include salts with trimethylamine, triethylamine, pyridine, picoline, 2 , 6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N, N'- dibenzylethylenediamine and the like.
• Preferable examples of the salt with inorganic acid include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
• the salt with the salt with organic base include salts with trimethylamine, triethylamine, pyridine, picoline, 2 , 6-lutidine, ethanolamine, diethanolamine, triethanolamine, cyclohexylamine, dicyclohexylamine, N, N'- dibenzylethylenediamine and the like.
• organic acid include salts with formic acid, acetic acid, trifluoroacetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p- toluenesulfonic acid and the like.
• salt with basic amino acid include salts with arginine, lysine, ornithine and the like.
• salt with acidic amino acid include salts with aspartic acid,, glutamic acid and the like.
• examples thereof include inorganic salts such as alkali metal salts (e.g., sodium salt, potassium salt etc.), alkaline earth metal salts (e.g., calcium salt,
• magnesium salt etc. and the like, ammonium salt etc.
• examples thereof include salts with inorganic acid such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like, and salts with organic acid such as acetic acid, phthalic acid, fumaric acid, oxalic acid, tartaric acid,
• maleic acid citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and the like.
• Compound (I) may be prepared by any process known to be applicable to the preparation of chemically-related compounds. Such processes are provided as one embodiment of the invention, and are illustrated by the following representative process. Necessary starting materials may be obtained by standard
• the starting material and/or the production intermediate for the compound (I), may form a salt. While the salt is not particularly limited as long as the reaction can be performed, examples thereof include those similar to the salts of
• the starting material has an amino group, a carboxyl group, a hydroxy group or a heterocyclic group
• these groups may be protected by a protecting group generally used in peptide chemistry and the like. By removing the protecting group as necessary after the reaction, the objective compound can be obtained.
• the protection and deprotection can be performed according to a method known per se, for example, the method described in "Protective Groups in Organic Synthesis, 3rd Ed", John Wiley and Sons, Inc. (1999) (Theodora W. Greene, Peter G. M. Wuts) .
• the protecting group include a tert-butylcarbamate group, a benzylcarbamate group, a benzyl group, a methyl group, an ethyl group, a tert-butyl and the like.
• the compound obtained in each step can be used directly as the reaction mixture or as a crude product for the next reaction. It can also be isolated from a reaction mixture by a conventional method, and can be easily purified by a

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Immunology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Physical Education & Sports Medicine (AREA)
• Rheumatology (AREA)
• Chemical Kinetics & Catalysis (AREA)
• General Chemical & Material Sciences (AREA)
• Orthopedic Medicine & Surgery (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Engineering & Computer Science (AREA)
• Pharmacology & Pharmacy (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Nitrogen Condensed Heterocyclic Rings (AREA)
• Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Priority Applications (7)

Applications Claiming Priority (2)

Related Child Applications (2)

Publications (1)

Family

ID=56740432

Family Applications (1)

Country Status (7)

Cited By (15)

Families Citing this family (1)

Citations (10)

Family Cites Families (7)

• 2016
  • 2016-07-22 CN CN201680042838.4A patent/CN108368127B/zh not_active Expired - Fee Related
  • 2016-07-22 EP EP16753995.6A patent/EP3325490B1/en active Active
  • 2016-07-22 JP JP2017566161A patent/JP6689297B2/ja not_active Expired - Fee Related
  • 2016-07-22 CA CA2993312A patent/CA2993312A1/en not_active Abandoned
  • 2016-07-22 DK DK16753995.6T patent/DK3325490T3/da active
  • 2016-07-22 WO PCT/JP2016/072244 patent/WO2017014323A1/en not_active Ceased
  • 2016-07-26 US US15/746,828 patent/US10745397B2/en not_active Expired - Fee Related
• 2020
  • 2020-07-06 US US16/921,338 patent/US20200339577A1/en not_active Abandoned

Patent Citations (10)

Non-Patent Citations (35)

Also Published As

Similar Documents

Legal Events