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US 10,308,627 B2Granted
Benzodiazepine derivatives as CCK2/gastrin receptor antagonists
AssigneeTrio Medicines Ltd
InventorsMalcolm James Boyce, Liv Thomsen, Donald Alan Gilbert, David Wood
Life of this patent
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Abstract
The invention relates to benzodiazepine derivatives of formula (A) useful as CCK2/gastrin receptor antagonists, their preparation and their use in the treatment or prevention of disorders associated with CCK2/gastrin receptors, disorders caused by or associated with hypergastrinaemia, and gastric acid-related disorders.
Claims29
A pharmaceutical composition comprising a compound of formula (A):
- or a pharmaceutically acceptable salt thereof,
- wherein, R1 and R2 are each, independently, H or C1-3 aliphatic, halo, or C1-3 haloaliphatic, or wherein R1 and R2 together with the intervening carbon atom to which they are bonded, form a C3-6 carbocyclic moiety;
- L is a bond or C1-3 alkylene;
- R3 is —OR6 or —SR6;
- W and X are, independently, hydrogen, halo, C1-8 alkyl or C1-8 alkoxy;
- and
- R4 and R5 are both, independently, a monocyclic aryl or heteroaryl, optionally substituted with one or more substituents independently selected from halo, hydroxy, amino, nitro, carboxyl, carboxamido, cyano, —SO3H, and optionally substituted C1-8 alkyl, C1-8 alkoxy, C1-8 alkylamino or alkyl)amino;
- R6 is hydrogen, —C(O)R, alkyl, —P(O)(OH)2, —P(O)(O(C1-6)alkyl)2, an alkylcarbonyloxyalkyl, (C1-6)alkoxycarbonylaminomethyl, succinoyl, or a α-aminoalkylcarbonyl;
- R is an optionally substituted aliphatic, heteroaliphatic, aromatic, or heteroaromatic moiety;
- and optionally one or more pharmaceutically acceptable excipient(s).
7 more elements
A compound of formula (C)
- or a pharmaceutically acceptable salt thereof,
- wherein, R1 and R2 are each, independently, H, C1-3 aliphatic, halo, or C1-3 haloaliphatic, or wherein R1 and R2 together with the intervening carbon atom to which they are bonded, form a C3-6 carbocyclic moiety;
- L is a bond or C1-3 alkylene;
- Y is —O— or —S—;
- W and X are, independently, hydrogen, halo, C1-8 alkyl or C1-8 alkoxy;
- R4 and R5 are both, independently, a monocyclic aryl or heteroaryl, optionally substituted with one or more substituents independently selected from halo, hydroxy, amino, nitro, carboxyl, carboxamido, cyano, —SO3H, and optionally substituted C1-8 alkyl, C1-8 alkoxy, C1-8 alkylamino or alkyl)amino;
- and R7 is an optionally substituted aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety.
4 more elements
A process for preparing a compound of formula
- said process comprising the step of coupling a compound of formula (A-i) with a compound of formula (A-ii) to form a compound of formula (A-iii);
- wherein,
- R1 and R2 are each, independently, H or C1-3 aliphatic, halo, or C1-3 haloaliphatic, or wherein R1 and R2 together with the intervening carbon atom to which they are bonded, form a C3-6 carbocyclic moiety;
- L is a bond or C1-3 alkylene;
- W and X are, independently, hydrogen, halo, C1-8 alkyl or C1-8 alkoxy;
- R3 is —OR6, —SR6, —OC(O)R7 or —SC(O)R7;
- R6 is hydrogen or alkyl (preferably methyl);
- R7 is an optionally substituted aliphatic, heteroaliphatic, aromatic or heteroaromatic moiety;
- and
- R4′ and R5′ are, independently, a monocyclic aryl or heteroaryl, optionally substituted with one or more substituents independently selected from halo, hydroxy, amino, nitro, carboxyl, carboxamido, cyano, —SO3H, and optionally substituted C1-8 alkyl, C1-8 alkoxy, C1-8 alkylamino or di(C1-8alkyl)amino;
- or a protected form thereof,
- optionally wherein the process comprises the further step of deprotecting the compound of formula (A-iii) to form a compound of formula (A)
- wherein, R1, R2 L, W, X and R3 are as defined for formula (A-i) and R4 and R5 are both, independently, a monocyclic aryl or heteroaryl, optionally substituted with one or more substituents independently selected from halo, hydroxy, amino, nitro, carboxyl, carboxamido, cyano, —SO3H, and optionally substituted C1-8 alkyl, C1-8 alkoxy, C1-8 alkylamino or di(C1-8 alkyl)amino.
10 more elements
Dependencies are inferred from the claim text.