# US 2014/0155433 A1 · Biaryl derivatives as nachr modulators

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- Number: US 2014/0155433 A1
- Document ID: US20140155433A1
- Status: Published application
- Kind: A1
- Application number: 14/130,815
- Filed: 2012-07-02
- Published: 2014-06-05
- Earliest claimed: 2011-07-05
- Assignees: Lupin Limited
- Inventors: Neelima Sinha; Navnath Popat Karche; Girish Dhanraj Hatnapure; Anil Kashiram Hajare; Venkata P. Palle; Rajender Kumar Kamboj
- Web page: https://patentgrep.com/patent/US20140155433A1

## CPC

- C07D 277/56: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- A61K 31/381: having five-membered rings
- A61K 31/40: having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K 31/401: Proline; Derivatives thereof, e.g. captopril
- A61K 31/4025: not condensed and containing further heterocyclic rings, e.g. cromakalim
- A61K 31/4164: 1,3-Diazoles
- A61K 31/426: 1,3-Thiazoles
- A61K 31/427: not condensed and containing further heterocyclic rings
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- C07D 207/335: Radicals substituted by nitrogen atoms not forming part of a nitro radical
- C07D 277/28: Radicals substituted by nitrogen atoms
- C07D 277/30: Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 333/22: Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
- C07D 417/12: linked by a chain containing hetero atoms as chain links
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)

## Abstract

Disclosed is a compound of formula (I): wherein ‘D’, ‘E’, ‘m’, ‘n’ and R1-R4 are as described herein, as a modulator of nicotinic acetylcholine receptors particularly the α7 subtype, in a subject in need thereof, as well as analogues, prodrugs, isotopically substituted analogs, metabolites, pharmaceutically acceptable salts, polymorphs, solvates, isomers, clathrates, and co-crystal thereof, for use either alone or in combinations with suitable other medicaments, and pharmaceutical compositions containing such compounds and analogues. Also disclosed are a process of preparation of the compounds and the intended uses thereof in therapy, particularly in the prophylaxis and therapy of disorders such as Alzheimer's disease, mild cognitive impairment, senile dementia, and the like.

## Claims

### Claim 1

A compound of formula (I), its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers,
wherein,
‘D’ is selected from N and CR5;
‘E’ is selected from S and NR6;
with a proviso that when ‘E’ is NR6, ‘D’ is not selected as N;
R1 is selected from hydrogen or substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, halogen, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, cyano, nitro, (R7)(R8)N—, R7cC(═O)N(R8)—, (R7a)(R8)NC(=A1)N(R9)—, R7bOC(═O)NR8a—, R7bSO2N(R8a)—, R7A1-, (R7a)(R8)NC(═O)—, and R7bS(O)p—, wherein ‘p’ is an integer ranging from 1 to 2;
R2 is selected from substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7)(R8)N—, (R7)N(OR7c)—, and R7A1-;
R3 is selected independently at each occurrence from halogen, cyano, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7a)(R8a)NC(═O)—, R7aA1-, (R7b)C(═O)N(R8a)—, (R7a)(R8a)N—, (R7a)(R8a)NC(=A1)N(R9)—, (R7a)(R8a)NC(═O)O—, R7bOC(═O)N(R8a)—, R7bS(O)p—, wherein ‘p’ is an integer ranging from 1 to 2, and two R3s and the carbon atoms to which they are attached can combine to form an substituted- or unsubstituted-5 to 8 member cyclic system which may contain 1 to 3 heteroatoms/groups selected from —NH—, —S—, —O—, —C(═O)—, and —C(═S)—;
‘n’ is selected from 0, 1, 2 and 3;
R4 is selected independently at each occurrence from halogen, cyano, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7a)(R8a)NC(═O)—, R7aA1-, (R7b)C(═O)N(R8a)—, (R7a)(R8a)N—, and two R4s and the carbon atoms to which they are attached can combine to form a substituted- or unsubstituted-5 to 8 membered cyclic system which may contain 1 to 3 heteroatoms/groups such as —NH—, —S—, —O—, —C(═O)—, and —C(═S)—;
‘m’ is selected from 0, 1, 2 and 3;
R5 is selected from hydrogen, halogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7)(R8)N—, and R7cC(═O)—;
R6 is selected from hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, and R7cC(═O)—;
R7 and R8 are independently selected from hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl;
R7a, R8a, and R9 are independently selected from hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
R7b is selected from substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
R7c is selected from substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl;
the substituents on ‘alkyl’ and ‘alkenyl’ are selected from the group consisting of oxo, halogen, nitro, cyano, perhaloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, R10bA1-, R10aSO2—, R10aOC(═O)—, R10aC(═O)O—, R10N(H)C(═O)—, R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10N(H)—, R10N(alkyl)-, R10N(H)C(=A1)N(H)—, and R10N(alkyl)C(=A1)N(H)—;
the substituents on ‘cycloalkyl’ and ‘cycloalkenyl’ are selected from the group consisting of oxo, halogen, nitro, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, perhaloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, R10bA1-, R10aSO2—, R10aC(═O)—, R10aOC(═O)—, R10aC(═O)O—, R10(H)NC(═O)—, R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10(H)N—, R10(alkyl)N—, R10(H)NC(=A1)N(H)—, and R10(alkyl)NC(=A1)N(H)—;
the substituents on ‘aryl’ are selected from the group consisting of halogen, nitro, cyano, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, perhaloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted- or unsubstituted-heterocycle, alkyl-O—, perhaloalkyl-O—, alkyl(alkyl)N—, alkyl(H)N—, H2N—, alkyl-SO2—, perhaloalkyl-SO2—, alkyl-C(═O)N(alkyl)-, alkyl-C(═O)N(H)—, alkyl(alkyl)NC(═O)—, alkyl(H)NC(═O)—, H2NC(═O)—, alkyl(alkyl)NSO2—, alkyl(H)NSO2—, and H2NSO2—;
the substituents on ‘heteroaryl’ are selected from the group consisting of halogen, nitro, cyano, hydroxy, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-heterocycle, alkyl-O—, perhaloalkyl-O—, alkyl(alkyl)N—, alkyl(H)N—, H2N—, alkyl-SO2—, perhaloalkyl-SO2—, alkyl-C(═O)N(alkyl)-, alkyl-C(═O)N(H)—, alkyl(alkyl)NC(═O)—, alkyl(H)NC(═O)—, H2NC(═O)—, alkyl(alkyl)NSO2—, alkyl(H)NSO2—, and H2NSO2—;
the substituents on ring carbon of ‘heterocycle’ is selected from the group consisting of halogen, nitro, cyano, oxo, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-heterocyclyl, substituted- or unsubstituted-alkyl, R10bA1-, —R10aOC(═O)—, R10aC(═O)O—, R10(H)NC(O═)—, R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10(H)N—, R10(alkyl)N—, R10(H)NC(=A1)N(H)—, and R10(alkyl)NC(=A1)N(H)—;
the substituents on ring nitrogen of ‘heterocycle’ is selected from the group consisting of substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, R10aSO2—, R10aC(═O)—, R10aOC(═O)—, R10(H)NC(═O)—, and R10N(alkyl)C(═O)—;
the “5 to 8 membered cyclic system” is substituted with 1 to 3 substituents selected from the group consisting of halogen, nitro, cyano, aryl, heteroaryl, alkyl, alkenyl, alkynyl, R10aC(═O)—, R10aSO2—, R10bA1-, R10aOC(═O)—, R10aC(═O)O—, (R10)(H)NC(═O)—, (R10)(alkyl)NC(═O)—, R10aC(═O)N(H)—, (R10)(H)N—, (R10)(alkyl)N—, (R10)(H)NC(=A1)N(H)—, and (R10)(alkyl)NC(=A1)N(H)—;
R10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
R10a is selected from the group consisting of alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
R10b is selected from the group consisting of hydrogen, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
A1 is selected from S and O.

### Claim 2 (depends on 1)

The compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, as claimed in claim 1, wherein D is selected from the group consisting of —CH═, —C(alkyl)=, and N═.

### Claim 3 (depends on 1)

The compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, as claimed in claim 1, wherein E is selected from —S— and —N(alkyl)-.

### Claim 4 (depends on 1)

The compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, as claimed in claim 1, wherein R1 is selected as substituted- or unsubstituted-alkyl.

### Claim 5 (depends on 1)

The compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, as claimed in claim 1, wherein R2 is selected from substituted- or unsubstituted-alkyl and substituted- or unsubstituted-heterocyclyl.

### Claim 6 (depends on 1)

The compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, as claimed in claim 1, wherein R3 is selected from halogen, R7aA-, and (R7a)(R8a)N—; and p is preferably selected from 0 and 1.

### Claim 7 (depends on 1)

The compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, as claimed in claim 1, wherein m is selected as 0.

### Claim 8 (depends on 1)

The compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, as claimed in claim 1, wherein D is selected from —CH═, —C(alkyl)=, and —N═;
E is selected from —S— and —N(alkyl)-;
R1 is selected as substituted- or unsubstituted-alkyl;
R2 is selected from substituted- or unsubstituted-alkyl and substituted- or unsubstituted-heterocyclyl;
R3 is selected from halogen, R7aA-, and (R7a)(R8a)N—;
p is selected from 0 and 1; and m is selected as 0.

### Claim 9 (depends on 1)

The compound of formula (I), its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, as claimed in claim 1, wherein the compound is selected from—
2′-Methoxy-5′-(3-methyl-5-propionylthiophen-2-yl)-[1,1′-biphenyl]-4-sulfonamide;
2′-chloro-5′-(3-methyl-5-propionylthiophen-2-yl)-[1,1′-biphenyl]-4-sulfonamide;
3′-(3-methyl-5-propionylthiophen-2-yl)-[1,1′-biphenyl]-4-sulfonamide;
2′-(dimethylamino)-5′-(3-methyl-5-propionylthiophen-2-yl)-[1,1′-biphenyl]-4-sulfonamide;
2′-methoxy-5′-(4-methyl-2-(piperidine-1-carbonyl)thiazol-5-yl)-[1,1′-biphenyl]-4-sulfonamide;
2′-methoxy-5′-(4-methyl-2-(pyrrolidine-1-carbonyl)thiazol-5-yl)-[1,1′-biphenyl]-4-sulfonamide;
2′-chloro-5′-(4-methyl-2-(pyrrolidine-1-carbonyl)thiazol-5-yl)-[1,1′-biphenyl]-4-sulfonamide;
2′-methoxy-5′-(4-methyl-2-propionylthiazol-5-yl)-[1,1′-biphenyl]-4-sulfonamide;
5′-(3,4-dimethyl-5-propionylthiophen-2-yl)-2′-methoxy-[1,1′-biphenyl]-4-sulfonamide;
5′-(1,3-dimethyl-5-propionyl-1H-pyrrol-2-yl)-2′-methoxy-[1,1′-biphenyl]-4-sulfonamide (Compound 10).

### Claim 10 (depends on 1)

A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

### Claim 11 (depends on 1)

A method of preventing or treating a disease or its symptoms or a disorder mediated partially or completely by nicotinic acetylcholine receptors, said method comprising administering to a subject having or susceptible to said disease or its symptoms or disorder with a therapeutically effective amount of a compound of claim 1.

### Claim 12

A method of treating a disease or disorder or condition mediated partially or completely by nicotinic acetylcholine receptors in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers,
wherein,
‘D’ is selected from N and CR5;
‘E’ is selected from S and NR6;
with a proviso that when ‘E’ is NR6, ‘D’ is not selected as N;
R1 is selected from hydrogen or substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, halogen, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, cyano, nitro, (R7)(R8)N—, R7cC(═O)N(R8)—, (R7a)(R8)NC(=A1)N(R9)—, R7bOC(═O)NR8a—, R7bSO2N(R8a)—, R7A1-, (R7a)(R8)NC(═O)—, and R7bS(O)p—, wherein ‘p’ is an integer ranging from 1 to 2;
R2 is selected from substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7)(R8)N—, (R7)N(OR7c)—, and R7A1-;
R3 is selected independently at each occurrence from halogen, cyano, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7a)(R8a)NC(═O)—, R7aA1-, (R7b)C(═O)N(R8a)—, (R7a)(R8a)N—, (R7a)(R8a)NC(=A1)N(R9)—, (R7a)(R8a)NC(═O)O—, R7bOC(═O)N(R8a)—, R7bS(O)p—, wherein ‘p’ is an integer ranging from 1 to 2, and two R3s and the carbon atoms to which they are attached can combine to form an substituted- or unsubstituted-5 to 8 member cyclic system which may contain 1 to 3 heteroatoms/groups selected from —NH—, —S—, —O—, —C(═O)—, and —C(═S)—;
‘n’ is selected from 0, 1, 2 and 3;
R4 is selected independently at each occurrence from halogen, cyano, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7a)(R8a)NC(═O)—, R7aA1-, (R7b)C(═O)N(R8a)—, (R7a)(R8a)N—, and two R4s and the carbon atoms to which they are attached can combine to form a substituted- or unsubstituted-5 to 8 membered cyclic system which may contain 1 to 3 heteroatoms/groups such as —NH—, —S—, —O—, —C(═O)—, and —C(═S)—;
‘m’ is selected from 0, 1, 2 and 3;
R5 is selected from hydrogen, halogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7)(R8)N—, and R7cC(═O)—;
R6 is selected from hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, and R7cC(═O)—;
R7 and R8 are independently selected from hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl;
R7a, R8a, and R9 are independently selected from hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
R7b is selected from substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
R7c is selected from substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl;
the substituents on ‘alkyl’ and ‘alkenyl’ are selected from the group consisting of oxo, halogen, nitro, cyano, perhaloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, R10bA1-, R10aSO2—, R10aOC(═O)—, R10aC(═O)O—, R10N(H)C(═O)—, R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10N(H)—, R10N(alkyl)-, R10N(H)C(=A1)N(H)—, and R10N(alkyl)C(=A1)N(H)—;
the substituents on ‘cycloalkyl’ and ‘cycloalkenyl’ are selected from the group consisting of oxo, halogen, nitro, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, perhaloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, R10bA1-, R10aSO2—, R10aC(═O)—, R10aOC(═O)—, R10aC(═O)O—, R10(H)NC(═O)—, R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10(H)N—, R10(alkyl)N—, R10(H)NC(=A1)N(H)—, and R10(alkyl)NC(=A1)N(H)—;
the substituents on ‘aryl’ are selected from the group consisting of halogen, nitro, cyano, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, perhaloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted- or unsubstituted-heterocycle, alkyl-O—, perhaloalkyl-O—, alkyl(alkyl)N—, alkyl(H)N—, H2N—, alkyl-SO2—, perhaloalkyl-SO2—, alkyl-C(═O)N(alkyl)-, alkyl-C(═O)N(H)—, alkyl(alkyl)NC(═O)—, alkyl(H)NC(═O)—, H2NC(═O)—, alkyl(alkyl)NSO2—, alkyl(H)NSO2—, and H2NSO2—;
the substituents on ‘heteroaryl’ are selected from the group consisting of halogen, nitro, cyano, hydroxy, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-heterocycle, alkyl-O—, perhaloalkyl-O—, alkyl(alkyl)N—, alkyl(H)N—, H2N—, alkyl-SO2—, perhaloalkyl-SO2—, alkyl-C(═O)N(alkyl)-, alkyl-C(═O)N(H)—, alkyl(alkyl)NC(═O)—, alkyl(H)NC(═O)—, H2NC(═O)—, alkyl(alkyl)NSO2—, alkyl(H)NSO2—, and H2NSO2—;
the substituents on ring carbon of ‘heterocycle’ is selected from the group consisting of halogen, nitro, cyano, oxo, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-heterocyclyl, substituted- or unsubstituted-alkyl, R10bA1-, —R10aOC(═O)—, R10aC(═O)O—, R10(H)NC(═O)—, R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10(H)N—, R10(alkyl)N—, R10(H)NC(=A1)N(H)—, and R10(alkyl)NC(=A1)N(H)—;
the substituents on ring nitrogen of ‘heterocycle’ is selected from the group consisting of substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, R10aSO2—, R10aC(═O)—, R10aOC(═O)—, R10(H)NC(═O)—, and R10N(alkyl)C(═O)—;
the “5 to 8 membered cyclic system” is substituted with 1 to 3 substituents selected from the group consisting of halogen, nitro, cyano, aryl, heteroaryl, alkyl, alkenyl, alkynyl, R10aC(═O)—, R10aSO2—, R10bA1-, R10aOC(═O)—, R10aC(═O)O—, (R10)(H)NC(═O)—, (R10)(alkyl)NC(═O)—, R10aC(═O)N(H)—, (R10)(H)N—, (R10)(alkyl)N—, (R10)(H)NC(=A1)N(H)—, and (R10)(alkyl)NC(=A1)N(H)—;
R10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
R10a is selected from the group consisting of alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
R10b is selected from the group consisting of hydrogen, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
A1 is selected from S and O.

### Claim 13 (depends on 12)

The method of claim 12, wherein the disorder or condition or disease is selected from the group consisting of Alzheimer's disease, mild cognitive impairment, senile dementia, vascular dementia, dementia of Parkinson's disease, attention deficit disorder, attention deficit hyperactivity disorder, dementia associated with Lewy bodies, AIDS dementia complex, Pick's disease, dementia associated with Down's syndrome, Huntington's disease, cognitive deficits associated with traumatic brain injury, cognitive decline associated with stroke, poststroke neuroprotection, cognitive and sensorimotor gating deficits associated with schizophrenia, cognitive deficits associated with bipolar disorder, cognitive impairments associated with depression, acute pain, post-surgical or post-operative pain, chronic pain, inflammation, inflammatory pain, neuropathic pain, smoking cessation, need for new blood vessel growth associated with wound healing, need for new blood vessel growth associated with vascularization of skin grafts, and lack of circulation, arthritis, rheumatoid arthritis, psoriasis, Crohn's disease, ulcerative colitis, pouchitis, inflammatory bowel disease, celiac disease, periodontitis, sarcoidosis, pancreatitis, organ transplant rejection, acute immune disease associated with organ transplantation, chronic immune disease associated with organ transplantation, septic shock, toxic shock syndrome, sepsis syndrome, depression, and rheumatoid spondylitis.

### Claim 14 (depends on 12)

The method of claim 12, wherein the disease or disorder or condition is selected from the group classified or diagnosed as major or minor neurocognitive disorders, or disorders arising due to neurodegeneration.

### Claim 15 (depends on 12)

The method of claim 12, comprising administering a compound of formula I in combination with or as adjunct to medications utilized in the treatment of attention deficit hyperactivity disorders, schizophrenia, cognitive disorders such as Alzheimer's disease, Parkinson's dementia, vascular dementia or dementia associated with Lewy bodies, or traumatic brain injury.

### Claim 16 (depends on 12)

The method of claim 12, further comprising administering a compound of formula I in combination with or as an adjunct to acetylcholinesterase inhibitors, disease modifying drugs or biologics for neurodegenerative disorders, dopaminergic drugs, antidepressants, or a typical or an atypical antipsychotic.

### Claim 17 (depends on 1)

Use of a compound of claim 1 for preventing or treating a disease or its symptoms or a disorder mediated partially or completely by nicotinic acetylcholine receptors.

### Claim 18

Use of a compound of formula I, its tautomeric forms, its stereoisomers, its sulfoxides, its N-oxides, its pharmaceutically acceptable salts, its polymorphs, its solvates, its optical isomers, for treating a disease or disorder or condition,
wherein,
‘D’ is selected from N and CR5;
‘E’ is selected from S and NR6;
with a proviso that when ‘E’ is NR6, ‘D’ is not selected as N;
R1 is selected from hydrogen or substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, halogen, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, cyano, nitro, (R7)(R8)N—, R7cC(═O)N(R8)—, (R7a)(R8)NC(=A1)N(R9)—, R7bOC(═O)NR8a—, R7bSO2N(R8a)—, R7A1-, (R7a)(R8)NC(═O)—, and R7bS(O)p—, wherein ‘p’ is an integer ranging from 1 to 2;
R2 is selected from substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7)(R8)N—, (R7)N(OR7c)—, and R7A1-;
R3 is selected independently at each occurrence from halogen, cyano, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7a)(R8a)NC(═O)—, R7aA1-, (R7b)C(═O)N(R8a)—, (R7a)(R8a)N—, (R7a)(R8a)NC(=A1)N(R9)—, (R7a)(R8a)NC(═O)O—, R7bOC(═O)N(R8a)—, R7bS(O)p—, wherein ‘p’ is an integer ranging from 1 to 2, and two R3s and the carbon atoms to which they are attached can combine to form an substituted- or unsubstituted-5 to 8 member cyclic system which may contain 1 to 3 heteroatoms/groups selected from —NH—, —S—, —O—, —C(═O)—, and —C(═S)—;
‘n’ is selected from 0, 1, 2 and 3;
R4 is selected independently at each occurrence from halogen, cyano, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7a)(R8a)NC(═O)—, R7aA1-, (R7b)C(═O)N(R8a)—, (R7a)(R8a)N—, and two R4s and the carbon atoms to which they are attached can combine to form a substituted- or unsubstituted-5 to 8 membered cyclic system which may contain 1 to 3 heteroatoms/groups such as —NH—, —S—, —O—, —C(═O)—, and —C(═S)—;
‘m’ is selected from 0, 1, 2 and 3;
R5 is selected from hydrogen, halogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-heterocyclyl, (R7)(R8)N—, and R7cC(═O)—;
R6 is selected from hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, and R7cC(═O)—;
R7 and R8 are independently selected from hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl;
R7a, R8a, and R9 are independently selected from hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
R7b is selected from substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl;
R7c is selected from substituted- or unsubstituted-alkyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl;
the substituents on ‘alkyl’ and ‘alkenyl’ are selected from the group consisting of oxo, halogen, nitro, cyano, perhaloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, R10bA1-, R10aSO2—, R10aOC(═O)—, R10aC(═O)O—, R10N(H)C(═O)—,
R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10N(H)—, R10N(alkyl)-, R10N(H)C(=A1)N(H)—, and R10N(alkyl)C(=A1)N(H)—;
the substituents on ‘cycloalkyl’ and ‘cycloalkenyl’ are selected from the group consisting of oxo, halogen, nitro, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, perhaloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocyclyl, R10bA1-, R10aSO2—, R10aC(═O)—, R10aOC(═O)—, R10aC(═O)O—, R10(H)NC(═O)—, R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10(H)N—, R10(alkyl)N—, R10(H)NC(=A1)N(H)—, and R10(alkyl)NC(=A1)N(H)—;
the substituents on ‘aryl’ are selected from the group consisting of halogen, nitro, cyano, hydroxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, perhaloalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted- or unsubstituted-heterocycle, alkyl-O—, perhaloalkyl-O—, alkyl(alkyl)N—, alkyl(H)N—, H2N—, alkyl-SO2—, perhaloalkyl-SO2—, alkyl-C(═O)N(alkyl)-, alkyl-C(═O)N(H)—, alkyl(alkyl)NC(═O)—, alkyl(H)NC(═O)—, H2NC(═O)—, alkyl(alkyl)NSO2—, alkyl(H)NSO2—, and H2NSO2—;
the substituents on ‘heteroaryl’ are selected from the group consisting of halogen, nitro, cyano, hydroxy, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-heterocycle, alkyl-O—, perhaloalkyl-O—, alkyl(alkyl)N—, alkyl(H)N—, H2N—, alkyl-SO2—, perhaloalkyl-SO2—, alkyl-C(═O)N(alkyl)-, alkyl-C(═O)N(H)—, alkyl(alkyl)NC(═O)—, alkyl(H)NC(═O)—, H2NC(═O)—, alkyl(alkyl)NSO2—, alkyl(H)NSO2—, and H2NSO2—;
the substituents on ring carbon of ‘heterocycle’ is selected from the group consisting of halogen, nitro, cyano, oxo, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, perhaloalkyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, substituted- or unsubstituted-heterocyclyl, substituted- or unsubstituted-alkyl, R10bA1-, —R10aOC(═O)—, R10aC(═O)O—, R10(H)NC(═O)—, R10N(alkyl)C(═O)—, R10aC(═O)N(H)—, R10(H)N—, R10(alkyl)N—, R10(H)NC(=A1)N(H)—, and R10(alkyl)NC(=A1)N(H)—;
the substituents on ring nitrogen of ‘heterocycle’ is selected from the group consisting of substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-cycloalkyl, substituted- or unsubstituted-cycloalkenyl, substituted- or unsubstituted-aryl, substituted- or unsubstituted-heteroaryl, R10aSO2—, R10aC(═O)—, R10aOC(═O)—, R10(H)NC(═O)—, and R10N(alkyl)C(═O)—;
the “5 to 8 membered cyclic system” is substituted with 1 to 3 substituents selected from the group consisting of halogen, nitro, cyano, aryl, heteroaryl, alkyl, alkenyl, alkynyl, R10aC(═O)—, R10aSO2—, R10bA1-, R10aOC(═O)—, R10aC(═O)O—, (R10)(H)NC(═O)—, (R10)(alkyl)NC(═O)—, R10aC(═O)N(H)—, (R10)(H)N—, (R10)(alkyl)N—, (R10)(H)NC(=A1)N(H)—, and (R10)(alkyl)NC(=A1)N(H)—;
R10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
R10a is selected from the group consisting of alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
R10b is selected from the group consisting of hydrogen, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl;
A1 is selected from S and O.

### Claim 19 (depends on 18)

The use as claimed in claim 18, wherein the disease or disorder or condition is selected from the group classified or diagnosed as major or minor neurocognitive disorders, or disorders arising due to neurodegeneration.

### Claim 20 (depends on 18)

The use as claimed in claim 18, which is in combination with or as adjunct to medications utilized in the treatment of attention deficit hyperactivity disorders, schizophrenia, cognitive disorders, Alzheimer's disease, Parkinson's dementia, vascular dementia or dementia associated with Lewy bodies, and traumatic brain injury.

### Claim 21

(canceled)