Heteroaryl inhibitors of pad4 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2017147102 A1 2017-08-31 [WO2017147102] / 2017-08-31
申请号/申请日
2017WO-US18790 / 2017-02-22
发明人
DEVRAJ RAJESH;KUMARAVEL GNANASAMBANDAM;ATTON HOLLY;BEAUMONT EDWARD;GADOULEAU ELISE;GLEAVE LAURA;KERRY PHILIP STEPHEN;LECCI CRISTINA;MENICONI MIRCO;MONCK NAT;PALFREY JORDAN;PAPADOPOULOS KOSTAS;TYE HEATHER;WOODS PHILIP A;
申请人
PADLOCK THERAPEUTICS;
主分类号
IPC分类号
A61K-031/4184A61P-035/00C07D-401/14C07D-417/14C07D-471/04
摘要
(WO2017147102) The present invention provides compounds useful as inhibitors of PAD4, compositions thereof, and methods of treating PAD4-related disorders.
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
地址
代理人
代理机构
;
优先权号
2016US-62298726 2016-02-23
主权利要求
(WO2017147102)  CLAIMS  We claim: 1.  A compound of formula I':     I'   or a pharmaceutically acceptable salt thereof, wherein:   Rin A is    4 groups selected from fluorine, -CN, -OR, or C1-6 aliphatic optionally substituted with 1-3 fluorine atoms;   Ring B is a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur;   R1 is hydrogen, -Cy, or C1-6 aliphatic optionally substituted withEN DASHCy and optionally further substituted with 1-4 groups selected from fluorine, -CN, or -OR;   each -Cy is independently a 6-membered aryl ring containing 0-2 nitrogen atoms, or a 4-7 membered saturated monocyclic ring having 0-2 heteroatoms independently selected from    nitrogen, oxygen, or sulphur, whereinEN DASHCy is optionally substituted with 1-4 groups selected from fluorine, -CN, or -OR;   R2 is hydrogen, -CN, -OR, -Cy, or C1-10 aliphatic optionally substituted withEN DASHCy and optionally further substituted with 1-5 groups selected from fluorine,EN DASHCN, orEN DASHOR; or:    two R2 groups on the same carbon are optionally taken together to form =O;   n is 1, 2, or 3;   X1 is N or C(R3);   R3 isEN DASHR, halogen, orEN DASHOR;   each R is independently hydrogen or C1-6 aliphatic optionally substituted with 1-3 fluorine atoms;   L is selected from a covalent bond or a C1-6 membered straight or branched, saturated or unsaturated hydrocarbon chain wherein one methylene unit of L is optionally replaced byEN DASH S(O)2EN DASH orEN DASHC(O)N(Ry)-, wherein Ry is R orEN DASHCH2phenyl; and   R4 is halogen, R, phenyl, or a 5-6-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulphur, wherein R4 is optionally substituted with 1-4 groups independently selected from halogen, -CN, -OR, -C(O)OH, or C1-6 aliphatic optionally substituted with 1-3 fluorine atoms. 2.  The compound according to claim 1, wherein said compound is of formula I'-a:     I'-a   or a pharmaceutically acceptable salt thereof. 3.  The compound according to claim 1, wherein said compound is of formula I'-b:     I'-b   or a pharmaceutically acceptable salt thereof.   4. The compound according to any of claims 1 through 3, wherein Ring A is   ,    6.  The compound according to any of claims 1 through 5, wherein Ring B is a 6-membered heteroaryl ring having 1-2 nitrogens. 7.  The compound according to any of claims 1 through 5, wherein Ring B is a 5-membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. 8.  The compound according to claim 6, wherein Ring B is pyridyl. 9.  The compound according to claim 7, wherein Ring B is imidazolyl, pyrazolyl, pyrrolyl, or thiazolyl.    10. The compound according to claim 9, wherein Ring B is pyrrolyl. 11.  The compound according to any of claims 1 through 10, wherein R4 is phenyl or pyridyl. 12.  The compound according to claim 1, wherein said compound is selected from those depicted in Table 1. 13.  A pharmaceutically acceptable composition comprising the compound according to any of claims 1 through 12, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. 14.  The composition according to claim 13, in combination with an additional therapeutic agent. 15.  A method of inhibiting PAD4 in a subject or in a biological sample comprising the step of contacting the PAD4 with a compound according to any of claims 1 through 12. 16.  A method of treating a PAD4-mediated disease, disorder, or condition in a subject in need thereof comprising the step of administering to said subject the composition according to claim 13. 17.  The method according to claim 16, wherein said subject is a human subject. 18.  The method according to claim 16, wherein said subject is a veterinary subject. 19.  The method according to claim 16, wherein the PAD4-mediated disease, disorder, or condition is selected from the group consisting of acid-induced lung injury, acne (PAPA), acute lymphocytic leukemia, acute, respiratory distress syndrome, Addison's disease, adrenal hyperplasia, adrenocortical insufficiency, ageing, AIDS, alcoholic hepatitis, alcoholic hepatitis, alcoholic liver disease, allergen induced asthma, allergic bronchopulmonary, aspergillosis, allergic conjunctivitis, alopecia, Alzheimer's disease, amyloidosis, amyotropic lateral sclerosis,    and weight loss, angina pectoris, angioedema, anhidrotic ecodermal dysplasia-ID, ankylosing spondylitis, anterior segment, inflammation, antiphospholipid syndrome, aphthous stomatitis, appendicitis, arthritis, asthma, atherosclerosis, atopic dermatitis, autoimmune diseases, autoimmune hepatitis, bee sting-induced inflammation, behcet's disease, Behcet's syndrome, Bells Palsey, berylliosis, Blau syndrome, bone pain, bronchiolitis, burns, bursitis, cancer, cardiac hypertrophy, carpal tunnel syndrome, catabolic disorders, cataracts, cerebral aneurysm, chemical irritant-induced inflammation, chorioretinitis, chronic heart failure, chronic lung disease of prematurity, chronic lymphocytic leukemia, chronic obstructive pulmonary disease, colitis, complex regional pain syndrome, connective tissue disease, corneal ulcer, crohn's disease, cryopyrin-associated periodic syndromes, cyrptococcosis, cystic fibrosis, deficiency of the interleukin-1EN DASHreceptor antagonist (DIRA), dermatitis, dermatitis endotoxemia, dermatomyositis, diffuse intrinsic pontine glioma, endometriosis, endotoxemia, epicondylitis, erythroblastopenia, familial amyloidotic polyneuropathy, familial cold urticarial, familial mediterranean fever, fetal growth retardation, glaucoma, glomerular disease, glomerular nephritis, gout, gouty arthritis, graft-versus-host disease, gut diseases, head injury, headache, hearing loss, heart disease, hemolytic anemia, Henoch-Scholein purpura, hepatitis, hereditary periodic fever syndrome, herpes zoster and simplex, HIV-1, Hodgkin's disease, Huntington's disease, hyaline membrane disease, hyperammonemia, hypercalcemia, hypercholesterolemia, hyperimmunoglobulinemia D with recurrent fever (HIDS), hypoplastic and other anemias, hypoplastic anemia, idiopathic thrombocytopenic purpura, incontinentia pigmenti, infectious mononucleosis, inflammatory bowel disease, inflammatory lung disease, inflammatory neuropathy, inflammatory pain, insect bite-induced inflammation, iritis, irritant-induced inflammation, ischemia/reperfusion, juvenile rheumatoid arthritis, keratitis, kidney disease, kidney injury caused by parasitic infections, kidney injury caused by parasitic infections, kidney transplant rejection prophylaxis, leptospiriosis, leukemia, Loeffler's syndrome, lung injury, lung injury, lupus, lupus, lupus nephritis, lymphoma, meningitis, mesothelioma, mixed connective tissue disease, Muckle-Wells syndrome (urticaria deafness amyloidosis), multiple sclerosis, muscle wasting, muscular dystrophy, myasthenia gravis, myocarditis, mycosis fungiodes, mycosis fungoides, myelodysplastic syndrome, myositis, nasal sinusitis, necrotizing enterocolitis, neonatal onset multisystem inflammatory disease (NOMID), nephrotic syndrome, neuritis, neuropathological diseases, non-allergen induced asthma, obesity, ocular allergy, optic neuritis, organ transplant,    osterarthritis, otitis media, paget's disease, pain, pancreatitis, Parkinson's disease, pemphigus, pericarditis, periodic fever, periodontitis, peritoneal endometriosis, pertussis, pharyngitis and adenitis (PFAPA syndrome), plant irritant-induced inflammation, pneumonia, pneumonitis, pneumosysts infection, poison ivy/ urushiol oil-induced inflammation, polyarteritis nodosa, polychondritis, polycystic kidney disease, polymyositis, psoriasis, psoriasis, psoriasis, psoriasis, psychosocial stress diseases, pulmonary disease, pulmonary hypertension, pulmonayr fibrosis, pyoderma gangrenosum, pyogenic sterile arthritis, renal disease, retinal disease, rheumatic carditis, rheumatic disease, rheumatoid arthritis, sarcoidosis, seborrhea, sepsis, severe pain, sickle cell, sickle cell anemia, silica-induced disease, Sjogren's syndrome, skin diseases, sleep apnea, solid tumors, spinal cord injury, Stevens-Johnson syndrome, stroke, subarachnoid hemorrhage, sunburn, temporal arteritis, tenosynovitis, thrombocytopenia, thyroiditis, tissue transplant, TNF receptor associated periodic syndrome (TRAPS), toxoplasmosis, transplant, traumatic brain injury, tuberculosis, type 1 diabetes, type 2 diabetes, ulcerative colitis, urticarial, uveitis, and Wegener's granulomatosis. 20.  The method according to claim 16, wherein the PAD4-mediated disease, disorder, or condition is selected from rheumatoid arthritis, vasculitis, systemic lupus erythematosus, ulcerative colitis, cancer, cystic fibrosis, asthma, cutaneous lupus erythematosis, and psoriasis.
法律状态
(WO2017147102) LEGAL DETAILS FOR WO2017147102  Actual or expected expiration date=2019-08-23    Legal state=ALIVE    Status=PENDING     Event publication date=2017-02-22  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2017018790  Application date=2017-02-22  Standardized application number=2017WO-US18790     Event publication date=2017-08-31  Event code=WO/A1  Event type=Examination events  Published application with search report  Publication country=WO  Publication number=WO2017147102  Publication stage Code=A1  Publication date=2017-08-31  Standardized publication number=WO2017147102
专利类型码
A1
国别省市代码
若您需要申请原文,请登录。

最新评论

暂无评论。

登录后可以发表评论

意见反馈
返回顶部