Dipeptidyl peptidase IV inhibitors; processes for their preparation and compositions thereof
AssigneeGlenmark Pharmaceuticals S.A.
InventorsAbraham Thomas, Balasubramanian Gopalan, V. S. Prasada Rao Lingam, Daisy Manish Shah
Life of this patent
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Abstract
The present invention relates to novel dipeptidyl peptidase IV (DPP-IV) inhibitors their analogs, isomers, pharmaceutical compositions, therapeutic uses and methods of making the same.
Claims29
A compound of general Formula (I)
- wherein:
- Y is —CH2—, CHF, or —CF2;
- X is NR3, O or S(O)m;
- m is 0, 1 or 2;
- the dotted line [----] in the carbocyclic ring represents an optional double bond;
- R1is a substituted or unsubstituted 6-membered heteroaryl ring having at least one nitrogen atom or a substituted or unsubstituted 6-membered heterocyclic ring having at least one nitrogen atom;
- R2 is hydrogen, nitrile (—CN), COOH, SO3H, B(OH)2, PO3R4R5, SO2NR4R5, a tetrazole, an amide, an ester or an acid anhydride;
- R3 is hydrogen, hydroxy, acetyl, substituted or unsubstituted alkyl, and substituted or unsubstituted alkoxy;
- and
- R4 and R5 may be same or different and are independently hydrogen, nitro, hydroxy, cyano, formyl, acetyl, halogen, substituted or unsubstituted amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkylakyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclic ring, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted heteroalkyl,
- or a tautomeric form, regioisomer, stereoisomer, enantiomer, diastereomer, solvate, N-oxide, or pharmaceutically acceptable salt thereof.
A compound selected from cis-(±)-6-(3-[2-(1-Pyrrolidinyl)-2-oxoethylamino]cyclopentylmethylamino)nicotinonitrile;
- 6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylamino)nicotinonitrile;
- 6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylamino)nicotinonitrile dihydrochioride;
- 6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylamino)nicotinonitrile maleate;
- 6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylamino)nicotinonitrile fumarate;
- 6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylamino)nicotinonitrile citrate;
- 6-((1S,3R)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethyl amino}cyclopentyl methylamino)nicotinonitrile;
- 6-((1S,3R)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl methylamino)nicotinonitrile dihydrochioride;
- 6-((1R,3S)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethyl amino}cyclopentyl methyl-amino)nicotinonitrile;
- 6-((1R,3S)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethyl amino}cyclopentyl methyl-amino)nicotinonitrile dihydrochioride;
- 6-((4SR,1RS)-4-{2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethyl amino}-2-cyclopentenyl-methylamino)nicotinonitrile;
- 6-((1RS,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethyl amino}cyclopentyl-methylamino)nicotinonitrile;
- 6-((1SR,3RS)-3-{2-[(2S,4S)-2-Cyano-4-fluoropyrrolidin-1-yl]-2-oxoethylamino}cyclopentylmethylamino)nicotinonitrile;
- 6-((1S,3R)-3-{2-[(2S, 4S)-2-Cyano-4-fluoropyrrolidin-1-yl]-2-oxoethylamino }cyclopentylmethylamino)nicotinonitrile;
- (2S)-1-{2-[(4S,1R)-4-(2-Pyridylsulfanylmethyl)cyclopent-2-ene amino]acetyl}-pyrrolidine-2carbonitrile;
- (2S)-1-{2-[(1S,3R)-3-(2-Pyridylsulfanylmethyl)cyclopentylamino]acetyl}-pyrrolidine-2carbonitrile;
- (2S)-1-{2-[(1S,3R)-3-(2-Pyridylsulfonylmethyl)cyclopentylamino]acetyl}-pyrrolidine-2-carbonitrile;
- 6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylsulfanyl)nicotinonitrile;
- 6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylsulfanyl)nictinonitrile maleate;
- 6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl)-2-oxoethylamino}cyclopentyl-methylsulfonyl)nicotinonitrile;
- (2S)-1-{2-[(3S,1R)-3-(2-Pyrimidinylsulfanylmethyl)cyclopentylamino]acetyl}-pyrrolidine-2-carbonitrile;
- (2S)-1-{2-[(3SR,1RS)-3-(2-Pyrimidinylaminomethyl)cyclopentylamino)acetyl}-pyrrolidine-2-carbonitrile;
- (2S)-1-{2-[(3SR,1RS)-3-(2-Pyrimidinylaminomethyl)cyclopentylamino)acetyl}-pyrrolidine-2-carbonitrile dihydrochloride;
- (2S)-1-{2-[(3S,1R)-3-(2-Pyrimidinylaminomethyl)cyclopentylamino)acetyl}-pyrrolidine-2-carbonitrile;
- (2S)-1-{2-[(3R,1S)-3-(2-Pyrimidinylaminomethyl)cyclopentylamino]acetyl}-pyrrolidine-2-carbonitrile;
- or a pharmaceutically acceptable salt thereof.
6-((1SR,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylamino)nicotinonitrile or a pharmaceutically acceptable salt thereof.
6-((1S,3R)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino}methylamino)nicotinonitrile or a pharmaceutically acceptable salt thereof.
6-((4SR,1RS)-4-{2-[(2S)-2-cyanopyrrolidin-1-yl]-2-oxoethylamino}cyclopentenyl-methylamino)nicotinonitrile or a pharmaceutically acceptable salt thereof.
6-((1RS,3RS)-3-{2-[(2S)-2-Cyanopyrrolidin-1-yl]-2-oxoethylamino }cyclopentyl-methylamino)nicotinonitrile or a pharmaceutically acceptable salt thereof.
6-((1S,3R)-3-{2-[(2S,4S)-2-Cyano-4-fluoropyrrolidin-1-yl]-2-oxoethylamino}cyclopentyl-methylamino)nicotinonitrile or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.