http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-116020-A1
Outgoing Links
| Predicate | Object |
|---|---|
| assignee | http://rdf.ncbi.nlm.nih.gov/pubchem/patentassignee/MD5_c7ad58d3c0b071069a8ee0cb8c8ba2e8 |
| classificationCPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/A61P31-12 http://rdf.ncbi.nlm.nih.gov/pubchem/patentcpc/C07D471-10 |
| classificationIPCInventive | http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61P35-00 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/A61K31-438 http://rdf.ncbi.nlm.nih.gov/pubchem/patentipc/C07D471-10 |
| filingDate | 2019-08-27-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| inventor | http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_3dc006dce726322974f7b5d48c7e28d6 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_cb5f91cd7b1ccac4e63fe048abfacb7c http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_d1e17d681a584d0d0e93e80cfbd7ce8e http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_6fa3348e9770ea4376d3ecef15587fcb http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_cd1c3b4f743e571d6ef17bfec07012a6 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_5c7114b4e744c58d097829a697f8d275 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_adcd8e3cc45d2cf06d9e17a9d5eac8e4 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_dc31e88bec172b7db6bf6498445ef7fe http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_f2eef3137852ea2ac540a94b4e1c5de6 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_b5e8807f9173763edf42e0597c93f6d5 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_fcfa99729871bd4f8c4dc29b369db2a3 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_0f2d0585d299509b98d3320ef54de894 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_b2190adda7d9cd712c78347902088350 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_f9f5e793896044c1e9af9fc9e77da63c http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_03d75709428a45415678750759c8ed5e http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_694d89a00ac80dcf3337ff997c0a8292 http://rdf.ncbi.nlm.nih.gov/pubchem/patentinventor/MD5_0f5295c71f8cc960b74076bab11cfe68 |
| publicationDate | 2021-03-25-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| publicationNumber | AR-116020-A1 |
| titleOfInvention | 3,9-DIAZAESPIRO [5.5] UNDECANO COMPOUNDS AS GGTase I INHIBITORS AND THEIR USE FOR THE TREATMENT OF HYPERPROLIFERATIVE DISEASES |
| abstract | Compounds derived from 3,9-diazaspiro [5.5] undecane, pharmaceutical compositions comprising them, intermediates for their preparation and their use in the treatment of hyperproliferative disorders, in particular cancer. Claim 1: A compound of the general formula (1), characterized in that: R¹ represents a group selected from phenyl and naphthyl, said phenyl and naphthyl group is optionally substituted, one, two, three or four times, each substituent is independently selected from a halogen atom or a group selected from C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, C₃₋₆-cycloalkyl, (C₃₋₆-cycloalkyl) - (C₁₋₃-alkyl) -, (C₃₋₆-cycloalkyloxy) - (C₁₋₃-alkyl) -, C₁₋₆-hydroxyalkyl, (C₁₋₂-alkoxy) - (C₁₋₆-alkyl) -, C₁₋₆-haloalkyl, C₁₋₆-alkoxy, (C₃₋₆-cycloalkyl) - (C₁₋₃-alkoxy) -, C₂₋₆-hydroxyalkoxy, (C₁₋₂-alkoxy) - (C₂₋₆-alkoxy) -, (C₁₋₂-alkoxy) - (alkyl -C₁₋₂) -CH (OH) - (C₁₋₂-alkoxy) -, (C₁₋₆-alkyl) -S- (C₁₋₆-alkoxy) -, C₁₋₆-haloalkoxy, (C₁₋-haloalkoxy ₂) - (C₁₋₆-alkyl) -, C₃₋₆-cycloalkyloxy, C₁₋₆-cyanoalkoxy, phenyl, 5- or 6-membered heteroaryl, (5- or 6-membered heteroaryl) oxy-, (5- or 6-membered heteroaryl members) - (C₁₋₃-alkyl) -, (5- or 6-membered heteroaryl) - (C₁₋₃-alkoxy) -, phenyl- (al chyl-C₁₋₃) -, phenyl- (alkoxy-C₁₋₃) -, phenoxy, phenoxy- (alkyl-C₁₋₃) -, phenoxy- (alkoxy-C₂₋₃) -, -SH, -S- ( C₁₋₆-alkyl), -S (= O) - (C₁₋₆-alkyl), -S (= O) ₂- (C₁₋₆-alkyl), -S- (C₃₋₆-cycloalkyl), - S (= O) - (C₃₋₆-cycloalkyl), -S (= O) ₂- (C₃₋₆-cycloalkyl), -S- (C₁₋₆-haloalkyl), -S (= O) - (haloalkyl -C₁₋₆), -S (= O) ₂- (haloalkyl-C₁₋₆), -S-phenyl, -S (= O) -phenyl, -S (= O) ₂-phenyl, cyano, hydroxy, -N (R⁵) (R⁶), - (C₁₋₄-alkyl) -N (R⁵) (R⁶), (R⁵) (R⁶) N- (C₂₋₃-alkoxy) -, 4- to 7-membered heterocycloalkyl, (4- to 7-membered heterocycloalkyl) oxy-, - (C₁₋₄-alkyl) - (4- to 7-membered heterocycloalkyl), (4- to 7-membered heterocycloalkyl) - (C₁₋₃-alkoxy) -, -C ( = O) N (R⁵) (R⁶), - (C₁₋₃-alkyl) -C (= O) N (R⁵) (R⁶), (R⁵) (R⁶) NC (= O) - (C₁₋-alkoxy ₃) -, -C (= O) OR⁷, - (C₁₋₃-alkyl) -C (= O) OR⁷, R⁷OC (= O) - (C₁₋₃-alkoxy) -, -C (= O) R⁷ , - (C₁₋₃-alkyl) -C (= O) R⁷ and (C₁₋₂-alkoxy) - (C₂₋₃-alkoxy) ₙ-, or two substituents of said phenyl group, when they are attached to ring atoms adjacent units are optionally joined together in such a way that together amente form a group selected from - (CH₂) ₃-, - (CH₂) ₄-, -O- (CH₂) ₂-, - (CH₂) ₂-O-, -CH₂-O-CH₂-, -O- ( CH₂) ₃-, - (CH₂) ₃-O-, -CH₂-O- (CH₂) ₂-, - (CH₂) ₂-O-CH₂-, -O-CH₂-O-, -O- (CH₂) ₂-O-, -N (R⁷) - (CH₂) ₂-, - (CH₂) ₂-N (R⁷) -, -CH₂-N (R⁷) -CH₂-, -N (R⁷) - (CH₂) ₃ -, - (CH₂) ₃-N (R⁷) -, -CH₂-N (R⁷) - (CH₂) ₂-, - (CH₂) ₂-N (R⁷) -CH₂-, -N (R⁷) - (CH₂ ) ₂-N (R⁷) -, -N (R⁷) - (CH₂) ₂-O- and -O- (CH₂) ₂-N (R⁷) -, where n represents an integer of 2, 3, 4 or 5, wherein said 4- to 7-membered heterocycloalkyl group and (4- to 7-membered heterocycloalkyl) part of said (4- to 7-membered heterocycloalkyl) oxy group, - (C₁₋₄-alkyl) - (4-membered heterocycloalkyl) group a 7-membered) and group (4- to 7-membered heterocycloalkyl) - (C alco-alkoxy) - is connected to the rest of the molecule by a carbon atom of the 4- to 7-membered heterocycloalkyl group, and wherein said heterocycloalkyl group from 4 to 7 and the (4- to 7-membered heterocycloalkyl) part of said group (4- to 7-membered heterocycloalkyl) oxy-, group - (C₁₋₄-alkyl) - ( 4-7 membered heterocycloalkyl) and the group (4-7 membered heterocycloalkyl) - (C₁₋₃-alkoxy) - is optionally substituted, once or twice, each substituent is independently selected from a halogen atom or a selected group C₁₋₂-alkyl, C₁₋₂-haloalkyl, C₁₋₂-hydroxyalkyl, cyano, hydroxy, C₁₋₂-alkoxy, C₃₋₄-cycloalkyl, -N (R⁵) (R⁶), -C (= O) OR⁸ and oxo, and wherein said phenyl and phenoxy group, and the phenyl part of said phenyl- (C₁₋₃-alkyl) -, phenyl- (C₁₋₃-alkoxy) -, phenoxy- (C₁₋-alkyl) group ₃) -, phenoxy- (C₂₋₃-alkoxy) -, -S-phenyl, -S (= O) -phenyl and -S (= O) ₂-phenyl, and said 5- or 6-membered heteroaryl group, and the (5- or 6-membered heteroaryl) part of said group (5- or 6-membered heteroaryl) oxy-, (5- or 6-membered heteroaryl) - (C₁₋₃-alkyl) - and (5- or 6-membered heteroaryl) - (C₁₋₃-alkoxy) is optionally substituted, once or twice, each substituent is independently selected from a halogen atom or a group selected from C₁₋₂-alkyl, haloal chyl-C₁₋₂, cyano, hydroxy, alkoxy-C₁₋₂, cycloalkyl-C₃₋₄ and -N (R⁵) (R⁶); R² represents a group selected from 5 or 6 membered phenyl, naphthyl and heteroaryl, whose 5 or 6 membered phenyl, naphthyl and heteroaryl group is optionally substituted one, two, three or four times, each substituent is independently selected from one atom halogen or a group selected from C₁₋₆-alkyl, C₂₋₆-alkenyl, C₂₋₆-alkynyl, C₃₋₆-cycloalkyl, C₄₋₇-cycloalkenyl, C₄₋₇-hydroxycycloalkenyl, (C₁₋₂-alkoxy) - (C₃₋₆-alkenyl) -, C₁₋₆-hydroxyalkyl, C₁₋₆-haloalkyl, C₁₋₆-alkoxy, C₁₋₆-haloalkoxy, C₃₋₆-cycloalkyloxy, -SH, -S- (C₁-alkyl ₋₆), -S (= O) - (C₁₋₆-alkyl), -S (= O) ₂- (C₁₋₆-alkyl), -S- (C₁₋₆-haloalkyl), -S (= O) - (C₁₋₆-haloalkyl), -S (= O) ₂- (C₁₋₆-haloalkyl), -S- (C₃₋₆-cycloalkyl), -S (= O) - (C₃₋-cycloalkyl ₆), -S (= O) ₂- (C₃₋₆-cycloalkyl), cyano, hydroxy, -N (R⁵) (R⁶), -C (= O) N (R⁵) (R⁶), -C (= O) OR⁷, 4- to 7-membered heterocycloalkyl, 5-7-membered heterocycloalkenyl, phenyl and 5-6-membered heteroaryl, or two substituents of said phenyl group, when or are attached to adjacent ring atoms are optionally attached to each other such that together they form a group selected from - (CH₂) ₃-, - (CH₂) ₄-, -O- (CH₂) ₂-, - (CH₂) ₂-O-, -CH₂-O-CH₂-, -O- (CH₂) ₃-, - (CH₂) ₃-O-, -CH₂-O- (CH₂) ₂-, - (CH₂) ₂-O- CH₂-, -O-CH₂-O- and -O- (CH₂) ₂-O-, wherein said 4- to 7-membered heterocycloalkyl group and the 5- to 7-membered heterocycloalkenyl group is connected to the rest of the molecule by a carbon atom of said 4 to 7 membered heterocycloalkyl group and 5 to 7 membered heterocycloalkenyl group, and wherein said 4 to 7 membered heterocycloalkyl group and 5 to 7 membered heterocycloalkenyl group is optionally substituted one or two times, each substituent is independently selected from a halogen atom or a group selected from C₁₋₂-alkyl, C₁₋₂-haloalkyl, cyano, hydroxy, C₁₋₂-alkoxy, C₃₋₄-cycloalkyl, -N (R⁵) (R⁶) and oxo, and wherein said phenyl group and the 5- to 6-membered heteroaryl group are optional Onally substituted once or twice, each substituent is independently selected from a halogen atom or a group selected from C₁₋₂-alkyl, C₁₋₂-haloalkyl, cyano, hydroxy, C₁₋₂-alkoxy, C₃₋₄-cycloalkyl, and -N (R⁵) (R⁶); R³ represents a hydrogen atom, a halogen atom, or a group selected from C₁₋₄-alkyl, C₂₋₄-alkenyl, C₂₋₄-alkynyl, C₃₋₆-cycloalkyl, C₁₋₄-hydroxyalkyl, C₁-haloalkyl ₋₄, C₁₋₄-alkoxy, C₂₋₆-hydroxyalkoxy, (C₁₋₂-alkoxy) - (C₂₋₆-alkoxy) -, C₁₋₄-haloalkoxy, C₃₋₆-cycloalkyloxy, phenyl, phenoxy, phenyl- ( C₁₋₂-alkyl) -, phenyl- (C₁₋₂-alkoxy) -, (5- or 6-membered heteroaryl) oxy, (5- or 6-membered heteroaryl) - (C₁₋₃-alkoxy), hydroxy, cyano, -N (R⁵) (R⁶), - (C₁₋₂-alkyl) -N (R⁵) (R⁶), (R⁵) (R⁶) N- (C₂₋₃-alkoxy) -, C₄₋₇-heterocycloalkyl, - (C₁₋₂-alkyl) - (C₄₋₇-heterocycloalkyl), (4- to 7-membered heterocycloalkyl) - (C₁₋₃-alkoxy) -, (C₁₋₂-haloalkoxy) - (C₁₋₂-alkyl) - , (C₁₋₂-alkoxy) - (C₁₋₂-alkyl) -, (C₃₋₄-cycloalkyloxy) - (C₁₋₂-alkyl) -, -C (= O) N (R⁵) (R⁶) and - C (= O) OR⁷, wherein said 4- to 7-membered heterocycloalkyl group and the (4- to 7-membered heterocycloalkyl) part of said group - (C₁₋₂-alkyl) - (4- to 7-membered heterocycloalkyl) and group (4- to 7-membered heterocycloalkyl) - (a lkoxy-C₁₋₃) - is connected to the rest of the molecule by a carbon atom of the 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group and the (4- to 7-membered heterocycloalkyl) part of said group - (C₁₋₂-alkyl) - (4- to 7-membered heterocycloalkyl) and the group (4- to 7-membered heterocycloalkyl) - (C₁₋₃-alkoxy) - is optionally substituted, once or twice, each substituent is independently selected from a halogen atom or a group selected from C₁₋₂-alkyl, C₁₋₂-haloalkyl, cyano, hydroxy, C₁₋₂-alkoxy, C₃₋₄-cycloalkyl, -N (R⁵) (R⁶) and oxo, and wherein said cycloalkyl group and said phenyl group, and the phenyl part of said phenoxy group, phenyl- (C₁₋₂-alkyl) - and phenyl- (C₁₋₂-alkoxy) -, and the (heteroaryl of 5 or 6 membered) part of said group (5- or 6-membered heteroaryl) oxy- and group (5- or 6-membered heteroaryl) - (C₁₋₃-alkoxy) - is optionally substituted, once or twice, each substituent is selected Independent from a halogen atom or a group selected from C₁₋₂-alkyl, C₁₋₂-haloalkyl, cyano, hydroxy, C₁₋₂-alkoxy, and -N (R⁵) (R⁶); R⁴ represents a hydrogen atom, a halogen atom, or a group selected from C₁₋₄-alkyl, C₂₋₄-alkenyl, C₂₋₄-alkynyl, C₃₋₆-cycloalkyl, C₁₋₄-hydroxyalkyl, C₁-haloalkyl ₋₄, phenyl, phenyl- (C₁₋₂-alkyl) -, - (C₁₋₂-alkyl -) - N (R⁵) (R⁶), C₄₋₇-heterocycloalkyl, - (C₁₋₂-alkyl) - ( heterocycloalkyl-C₄₋₇), (haloalkoxy-C₁₋₂) - (alkyl-C₁₋₂) -, (alkoxy-C₁₋₂) - (alkyl-C₁₋₂) - and (cycloalkyloxy-C₃₋₄) - ( alkyl-C₁₋₂) - wherein said 4- to 7-membered heterocycloalkyl group and the (4- to 7-membered heterocycloalkyl) part of said group - (C alqu-alkyl) - (4- to 7-membered heterocycloalkyl) is connected to the rest of the molecule by a carbon atom of the 4- to 7-membered heterocycloalkyl group, and wherein said 4- to 7-membered heterocycloalkyl group and the (4- to 7-membered heterocycloalkyl) part of said group - (C₁₋-alkyl ₂) - (4- to 7-membered heterocycloalkyl) is optionally substituted once or twice, each substituent independently selected from a halogen atom or a group selected from C₁₋₂-alkyl, C₁₋₂-haloalkyl, cyano, hydroxy, C₁₋₂-alkoxy, C₃₋₄-cycloalkyl, -N (R⁵) (R⁶) and oxo, and wherein said cycloalkyl group and said phenyl group, and the phenyl part of said phenyl- (C₁₋₃-alkyl) group is optionally substituted, once or twice, each substituent independently selected from a halogen atom or a group selected from alkyl- C₁₋₂, haloalkyl-C₁₋₂, cyano, hydroxy, alkoxy-C₁₋₂ and -N (R⁵) (R⁶), or R³ and R⁴ together with the carbon atom to which they are attached represent a cycloalkyl group of 3 to 8-membered, wherein said cycloalkyl group is optionally substituted, once or twice, each substituent is independently selected from a halogen atom or a group selected from C₁₋₂-alkyl, C₁₋₂-haloalkyl, C₁₋₂-alkoxy, cyano, hydroxy, and oxo; R⁵ and R⁶ represent, independently of each occurrence, a hydrogen atom or a group selected from alkyl-C₁₋₄, cycloalkyl-C₃₋₄, haloalkyl-C₂₋₄, hydroxyalkyl-C₂₋₄, (alkoxy-C₁₋₂) - (C₂₋₃-alkyl-), -C (= O) - (C₁₋₃-alkyl) and -C (= O) - (C₁₋₃-haloalkyl), or R⁵ and R⁶ together with the nitrogen to which are attached represent a nitrogen containing a 4- to 7-membered heterocycloalkyl group, wherein said 4- to 7-membered nitrogen-containing heterocycloalkyl group is optionally substituted, once or twice, each substituent is independently selected from a halogen atom or a group selected from C₁₋₄-alkyl, C₃₋₄-cycloalkyl, C₁₋₄-haloalkyl, C₁₋₄-hydroxyalkyl, (C₁₋₂-alkoxy) - (C₁₋₃-alkyl) - and oxo; R⁷ represents a hydrogen atom or a C₁₋₄-alkyl group; and R⁸ represents a C₁₋₄-alkyl group; or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, or a salt thereof, or a mixture thereof. Claim 19: Use of a compound of the general formula (2), characterized in that R¹ is as defined for the compound of the general formula (1) according to any of claims 1, 2 or 8, and wherein Rᵈ represents a group protective, for the preparation of a compound of the general formula (1) according to any of claims 1, 2 or 8. Claim 20: Use of a compound of the general formula (3) characterized in that R², R³ and R⁴ are as define for the compound of the general formula (1) according to any of claims 1, 2 or 8, for the preparation of a compound of the general formula (1) according to any of claims 1, 2 or 8. |
| priorityDate | 2018-09-03-04:00^^<http://www.w3.org/2001/XMLSchema#date> |
| type | http://data.epo.org/linked-data/def/patent/Publication |
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Total number of triples: 44.