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1. (WO2019008506) N-(3-(2-(4-CHLOROPHENOXY)ACETAMIDO)BICYCLO[1.1.1]PENTAN-1-YL)-2-CYCLOBUTANE-1-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ATF4 INHIBITORS FOR TREATING CANCER AND OTHER DISEASES
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Pub. No.: WO/2019/008506 International Application No.: PCT/IB2018/054912
Publication Date: 10.01.2019 International Filing Date: 02.07.2018
IPC:
C07C 233/74 (2006.01) ,C07D 211/38 (2006.01) ,C07D 211/40 (2006.01) ,C07D 207/16 (2006.01) ,A61K 31/165 (2006.01) ,A61P 35/00 (2006.01) ,A61P 25/28 (2006.01) ,A61P 25/16 (2006.01) ,A61P 3/10 (2006.01)
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
C
ACYCLIC OR CARBOCYCLIC COMPOUNDS
233
Carboxylic acid amides
64
having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
67
having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
74
with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a ring other than a six-membered aromatic ring
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
211
Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
04
with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
06
having no double bonds between ring members or between ring members and non-ring members
36
with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
38
Halogen atoms or nitro radicals
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
211
Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
04
with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
06
having no double bonds between ring members or between ring members and non-ring members
36
with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
40
Oxygen atoms
C CHEMISTRY; METALLURGY
07
ORGANIC CHEMISTRY
D
HETEROCYCLIC COMPOUNDS
207
Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
02
with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
04
having no double bonds between ring members or between ring members and non-ring members
10
with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
16
Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
K
PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
31
Medicinal preparations containing organic active ingredients
16
Amides, e.g. hydroxamic acids
165
having aromatic rings, e.g. colchicine, atenolol, progabide
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
35
Antineoplastic agents
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
25
Drugs for disorders of the nervous system
28
for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
25
Drugs for disorders of the nervous system
14
for treating abnormal movements, e.g. chorea, dyskinesia
16
Anti-Parkinson drugs
A HUMAN NECESSITIES
61
MEDICAL OR VETERINARY SCIENCE; HYGIENE
P
SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
3
Drugs for disorders of the metabolism
08
for glucose homeostasis
10
for hyperglycaemia, e.g. antidiabetics
Applicants:
GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED [GB/GB]; 980 Great West Road Brentford, Middlesex TW8 9GS, GB
Inventors:
CHEUNG, Mui; US
DEMARTINO, Michael P.; US
KALITA, Biswajit; IN
Priority Data:
20171102330903.07.2017IN
Title (EN) N-(3-(2-(4-CHLOROPHENOXY)ACETAMIDO)BICYCLO[1.1.1]PENTAN-1-YL)-2-CYCLOBUTANE-1-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ATF4 INHIBITORS FOR TREATING CANCER AND OTHER DISEASES
(FR) DÉRIVÉS DE N-(3-(2-(4-CHLOROPHÉNOXY)ACÉTAMIDO)BICYCLO[1.1.1]PENTAN-1-YL)-2-CYCLOBUTANE-1-CARBOXAMIDE ET COMPOSÉS APPARENTÉS EN TANT QU'INHIBITEURS ATF4 POUR LE TRAITEMENT DU CANCER ET D'AUTRES MALADIES
Abstract:
(EN) The invention is directed to substituted bridged cycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein X, a, b, C, D, L2, L3, Y1, Y2, R2, R4, R5, R6, z2, z4, z5, and z6 are as defined herein, and salts thereof. The invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to compounds for use in methods of inhibiting the ATF4 (activating transcription factor 4) pathway and treatment of disorders associated therewith, such as e.g. cancer, neurodegenerative diseases and many other diseases, using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. Preferred compounds of the invention are N-(3-(2-(4-chlorophenoxy) acetamido)bicyclo[1.1.1]pentan-l-yl)-2-cyclobutane-l-carboxamide derivatives and related compounds.
(FR) L'invention concerne des dérivés de cycloalcanes pontés substitués. L'invention concerne particulièrement des composés de formule (II), dans laquelle X, a, b, C, D, L2, L3, Y1, Y2, R2, R4, R5, R6, z2, z4, z5 et z6 sont tels que définis dans la description; l'invention concerne également des sels de ces composés. L'invention concerne en outre des compositions pharmaceutiques comprenant un composé selon l'invention. L'invention concerne en outre des composés destinés à être utilisés dans des procédés d'inhibition de la voie ATF4 (facteur 4 d'activation de la transcription) et dans le traitement de troubles associés à celle-ci, comme par exemple le cancer, des maladies neurodégénératives et d'autres maladies, à l'aide d'un composé de l'invention ou d'une composition pharmaceutique comprenant un composé de l'invention. Les composés préférés selon l'invention sont des dérivés de N-(3-(2-(4-chlorophénoxy)acétamido)bicyclo [1.1.1]pentan-l-yl)-2-cyclobutane-l-carboxamide et des composés apparentés.
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Designated States: AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW
African Regional Intellectual Property Organization (ARIPO) (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Office (AM, AZ, BY, KG, KZ, RU, TJ, TM)
European Patent Office (EPO) (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, KM, ML, MR, NE, SN, TD, TG)
Publication Language: English (EN)
Filing Language: English (EN)