JPWO2021092322A5

JPWO2021092322A5 -

Info

Publication number: JPWO2021092322A5
Application number: JP2022526226A
Authority: JP
Publication date: 2023-11-14

Claims

Compound of formula (0):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof (wherein
R ¹ is substituted or unsubstituted C _1-12 alkyl or substituted or unsubstituted C _1-12 heteroalkyl;
R ² is hydrogen, substituted or unsubstituted C _1-12 alkyl, substituted or unsubstituted C _1-12 heteroalkyl, substituted or unsubstituted 3-13 membered heterocyclyl-C _1-12 -alkyl, substituted or unsubstituted 3-12 13-membered carbocyclyl-C _1-12 -alkyl, or a nitrogen protecting group,
When R ² is unsubstituted methyl, R ¹ is not unsubstituted ethyl,
R ³ is hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, -OR ^a , -COOR ^a , -COR ^a , -N(R ^a ) ₂ , -CN, or -(C=O)N( R ^a ) ₂ ,
Each instance of R ^a is independently hydrogen, substituted or unsubstituted C _1-6 alkyl, an oxygen protecting group if attached to an oxygen atom, or a nitrogen protecting group if attached to a nitrogen atom. can be,
Each instance of R ⁴ independently represents hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, -OR ^a , -COOR ^a , -COR ^a , -N(R ^a ) ₂ , -CN, or - (C=O)N(R ^a ) ₂ ,
Each instance of R ⁵ independently represents hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, -OR ^a , -COOR ^a , -COR ^a , -N(R ^a ) ₂ , -CN, or - (C=O)N(R ^a ) ₂ ,
R ⁶ is hydrogen, substituted or unsubstituted C _1-6 alkyl, or a nitrogen protecting group;
Each instance of R ⁸ is independently hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl;
Each instance of R ⁹ independently represents hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, -OR ^a , -COOR ^a , -COR ^a , -N(R ^a ) ₂ , -CN, or - (C=O)N(R ^a ) ₂ , or two instances of R ⁹ are linked to form a 3- to 13-membered heterocyclyl, a 3- to 13-membered heterocyclyl, a 6- to 12-membered aryl ring, or a 5- to 14-membered aryl ring. forming a heteroaryl ring,
n is an integer from 0 to 4 (including both extreme values),
m is an integer from 0 to 3 (including both extreme values),
p is an integer from 0 to 3 (including both extreme values),
q is an integer selected from 0 and 1, provided that the compound has the formula:
).

(a) The compound has the formula (0a):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
(b) The compound has the formula (0b):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof; or (c ) The compound has the formula (0c):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
A compound according to claim 1.

(a) q is 0; or (b) q is 1.
A compound according to claim 1 or 2.

A compound according to any one of claims 1 to 3, wherein the two instances of R ⁹ are linked to form a 5-membered heteroaryl ring or a 5-membered heterocyclyl ring.

Compound of formula (I):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof (wherein
R ¹ is substituted or unsubstituted C _1-12 alkyl or substituted or unsubstituted C _1-12 heteroalkyl;
R ² is hydrogen, substituted or unsubstituted C _1-12 alkyl, substituted or unsubstituted C _1-12 heteroalkyl, substituted or unsubstituted 3-13 membered heterocyclyl-C _1-12 -alkyl, substituted or unsubstituted 3-12 13-membered carbocyclyl-C _1-12 -alkyl, or a nitrogen protecting group,
When R ² is unsubstituted methyl, R ¹ is not unsubstituted ethyl,
R ³ is hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, -OR ^a , -COOR ^a , -COR ^a , -N(R ^a ) ₂ , -CN, or -(C=O)N( R ^a ) ₂ ,
Each instance of R ^a is independently hydrogen, substituted or unsubstituted C _1-6 alkyl, an oxygen protecting group if attached to an oxygen atom, or a nitrogen protecting group if attached to a nitrogen atom. can be,
Each instance of R ⁴ independently represents hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, -OR ^a , -COOR ^a , -COR ^a , -N(R ^a ) ₂ , -CN, or - (C=O)N(R ^a ) ₂ ,
Each instance of R ⁵ independently represents hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, -OR ^a , -COOR ^a , -COR ^a , -N(R ^a ) ₂ , -CN, or - (C=O)N(R ^a ) ₂ ,
R ⁶ is hydrogen, substituted or unsubstituted C _1-6 alkyl, or a nitrogen protecting group;
Each instance of R ⁸ is independently hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl;
Each instance of R ⁹ independently represents hydrogen, halogen, substituted or unsubstituted C _1-6 alkyl, -OR ^a , -COOR ^a , -COR ^a , -N(R ^a ) ₂ , -CN, or - (C=O)N(R ^a ) ₂ ,
n is an integer from 0 to 4 (including both extreme values),
m is an integer from 0 to 3 (including both extreme values),
p is an integer from 0 to 3 (inclusive), provided that the compound has the formula:
).

(a) The compound has the formula (Iz):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
(b) The compound has formula (Ia):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
(c) The compound has formula (Ib):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof; or (d ) The compound has the formula (Ic):
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof. 5. The compound according to any one of 5.

(a) Is n 0?
(b) n is 1; or (c) n is 2.
A compound according to any one of claims 1 to 6.

Each R ⁹ is
(a) independently hydrogen, substituted or unsubstituted methyl, chloro, fluoro, methoxy, or _-NH2 ;
(b) is independently substituted or unsubstituted methyl, chloro, fluoro, methoxy, or _-NH2 ; or (c) is methyl;
A compound according to any one of claims 1 to 7.

(a) Is R ³ hydrogen, substituted or unsubstituted methyl, fluoro, chloro, -CN, or -COOR ^a ;
(b) R ³ is hydrogen, substituted or unsubstituted methyl, chloro, bromo, iodo, -CN, or -COOR ^a ;
(c) R ³ is hydrogen, substituted or unsubstituted methyl, -CN, or -COOR ^a ; or (d) R ³ is methyl or chloro.
A compound according to any one of claims 1 to 8.

(a) Is R ¹ substituted or unsubstituted C _1-3 alkyl;
A compound according to any one of claims 1 to 9, wherein (b) R ¹ is substituted or unsubstituted C _1-3 heteroalkyl; or (c) R ¹ is methyl or ethyl.

(a) R ² is substituted or unsubstituted C _1-6 alkyl or substituted or unsubstituted C _1-6 heteroalkyl;
(b) R ² is substituted or unsubstituted 3-6 membered heterocyclyl-C _1-6 -alkyl, or substituted or unsubstituted 3-6 membered carbocyclyl-C _1-6 -alkyl;
(c) is R ² substituted or unsubstituted propyl, substituted or unsubstituted isopropyl, substituted or unsubstituted butyl, or substituted or unsubstituted isobutyl;
(d) R ² is substituted or unsubstituted 3-6 membered heterocyclyl-C ₁ -alkyl, or substituted or unsubstituted 3-6 membered carbocyclyl-C ₁ -alkyl;
(e) R ² is substituted or unsubstituted 3-6 membered carbocyclyl-C _1-6 -alkyl or substituted or unsubstituted C _1-6 alkyl; or (f) R ² is unsubstituted 3-6 membered carbocyclyl-C 1-6 -alkyl; member carbocyclyl-C _1-2 -alkyl or substituted C _1-6 alkyl,
A compound according to any one of claims 1 to 10.

R ¹ and R ² are
(a) contains a total number of 4 or more carbon atoms; or (b) contains a total number of 4 or more non-hydrogen atoms;
A compound according to any one of claims 1 to 11.

The compound is
(a)
or a pharmaceutically acceptable salt, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
(b) I-466, I-467, I-468, I-482, I-483, I-484, I-485, I-486, I-487, I-488, I-489, I-491 , I-492, I-495, I-497, I-499, I-500, I-501, I-502, I-503, I-510, I-512, I-517, I-593, I -594, I-595, I-596, I-599, I-600, I-601, I-602, I-603, I-604, I-605, I-606, I-608, I-609 , I-610, I-611, I-619, I-620, I-626, I-629, I-631, I-639, I-652, I-658, I-662, I-663, I -677, I-685, I-689, I-690, I-T2106, I-T2107, I-T2120, I-696, I-T2162, I-T2163, I-697, I-T2165, I-T2166 , IT2167, IT2168, IT2169, IT2170, IT2171, IT2172, IT2174, IT2175, IT2176, IT2177, IT2178, IT2179, I -T2180, IT2181, IT2182, IT2183, IT2184, IT2185, IT2186, IT2187, IT2188, IT2206, IT2211, IT2212, IT2213 , IT2217, IT2218, IT2219, IT2223, IT2224, IT2225, IT2241, IT2242, IT2243, IT2244, IT2245, IT2246, I -T2247, IT2248, IT2249, IT2250, IT2251, IT2252, IT2253, IT2254, IT2255, IT2256, IT2257, and IT2258, or selected from the group consisting of pharmaceutically acceptable salts, hydrates, polymorphs, cocrystals, tautomers, stereoisomers, isotopically labeled derivatives, or prodrugs;
(c) I-674, I-676, I-679, I-681, I-683, I-684, I-687, I-T2101, I-T2102, I-T2109, I-T2135, I-T2136 , I-693, I-T2157, I-T2158, I-T2159, I-T2160, I-T2173, I-T2189, I-T2190, I-T2191, I-T2192, I-T2193, I-T2194, I -T2195, IT2196, IT2197, IT2198, IT2199, IT2200, IT2208, IT2209, IT2210, IT2214, IT2215, IT2216, IT2220 , I-T2221, I-T2222, I-T2226, I-T2227, I-T2228, I-698, I-T2230, I-T2231, I-T2232, I-T2233, I-T2234, IT2235, I -T2236, IT2237, IT2238, IT2239, and IT2240, or pharmaceutically acceptable salts, hydrates, polymorphs, cocrystals, tautomers, stereoisomers, isotopes thereof selected from the group consisting of body-labeled derivatives or prodrugs; or (d)
or a pharmaceutically acceptable salt, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
A compound according to any one of claims 1 to 12.

A compound,
(a)
selected from the group consisting of pharmaceutically acceptable salts, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, or prodrugs thereof;
(b)
or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
(c) I-481, I-597, I-624, I-630, and I-675, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, or tautomer thereof; is selected from the group consisting of isotope-labeled derivatives, stereoisomers, isotopically labeled derivatives, or prodrugs;
(d) I-331, I-496, I-511, I-450, and I-527, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, or tautomer thereof; or (e)
or a pharmaceutically acceptable salt, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug thereof;
Said compound.

A pharmaceutical composition comprising:
The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative or prodrug; and optionally a pharmaceutically acceptable excipient;
optionally further comprising an additional pharmaceutical agent, optionally said additional pharmaceutical agent being a chemotherapeutic agent or a differentiation agent;
The pharmaceutical composition.

A pharmaceutical composition for use in treating a disease or disorder in a subject, the composition comprising:
The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15;
Optionally, the disease or disorder is heart failure, dilated cardiomyopathy, pain, inflammation, acute distress syndrome, ventilator-induced lung injury, graft versus host disease (GCDH), pneumonia, pneumonitis, severe acute distress. Syndrome, arthritis, acute lung injury, colitis, inflammatory bowel disease (IBD), diabetes, obesity, axonal degeneration, impaired tissue repair, asthma, chronic obstructive pulmonary disease (COPD), osteoarthritis, osteoporosis, fibrosis Associated with sexual diseases, skin diseases, psoriasis, atopic dermatitis, UV-induced skin damage, autoimmune diseases, Alzheimer's disease, stroke, atherosclerosis, restenosis, glomerulonephritis, cachexia, and infectious diseases Inflammation, vascular inflammation, atherothrombotic disease, acquired immune deficiency syndrome (AIDS), adult respiratory distress syndrome, ataxia telangiectasia, atherogenic inflammatory disease, cardiovascular disorder, cerebrovascular disorder, acute coronary syndrome , polycystic ovary syndrome, preeclampsia, sepsis, septic shock, intrauterine infection, Crohn's disease (CD), ulcerative colitis (UC), neurodegenerative disorders, COVID-19, pulmonary inflammation, coronavirus an infectious disease, or a tumor; and/or optionally, said disease or disorder is
(a) inhibiting NAMPT in the subject;
(b) inhibiting the NAMPT pathway in the subject;
(c) reducing NAMPT signaling in the subject;
(d) inhibiting the production of nicotinamide mononucleotide in the subject;
(e) inhibiting the production of nicotinamide adenine dinucleotide in the subject;
(f) reducing inflammatory activity in the subject;
(g) reducing inflammatory cell infiltration in the subject;
(h) reducing cell proliferation in the subject; or (i) being treated by reducing cellular metabolic activity or condition in the subject;
The pharmaceutical composition.

further comprising an additional pharmaceutical agent, said additional pharmaceutical agent comprising said compound, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, stereoisomer thereof. 17. A pharmaceutical composition according to claim 16, which is used for administration before, simultaneously with, or after said composition.

A pharmaceutical composition for use in the treatment of cancer in a subject in need thereof, comprising:
The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15;
Optionally, the cancer comprises cancer stem cells; and/or Optionally, the cancer comprises:
(a) gastric cancer, gastrointestinal stromal tumor, ovarian cancer, lung cancer, breast cancer, pancreatic cancer, or prostate cancer;
(b) gastric cancer; optionally, said gastric cancer is gastric cancer subtype GS or gastric cancer subtype CIN;
(c) colorectal cancer; optionally said colorectal cancer is colorectal cancer subtype CMS2 or colorectal cancer subtype CMS4;
(d) testicular cancer;
(e) Liver cancer;
(f) endometrial cancer; optionally, said cancer is uterine cancer;
(g) small cell lung cancer;
(h) lymphoma; optionally, said lymphoma:
(1) Non-Hodgkin lymphoma;
(2) B-cell lymphoma;
(3) Large B-cell lymphoma;
(4) Burkitt lymphoma;
(5) Burkitt B cell lymphoma; or (6) large cell immunoblastic lymphoma;
(i) leukemia; optionally, said leukemia:
(1) acute myeloid leukemia; optionally, said acute myeloid leukemia:
(I) Undifferentiated acute myeloblastic leukemia (M0);
(II) acute myeloblastic leukemia with minimal maturation (M1);
(III) acute myeloblastic leukemia with maturation (M2);
(IV) acute promyelocytic leukemia (APL) (M3);
(V) Acute myelomonocytic leukemia (M4);
(VI) acute myelomonocytic leukemia with eosinophilia (M4 eos);
(VII) acute monocytic leukemia (M5);
(VIII) acute erythroleukemia (M6); or
(I) acute megakaryoblastic leukemia (M7);
(2) Acute monocytic leukemia;
(3) acute lymphocytic leukemia;
(4) B-cell acute lymphocytic leukemia;
(5) chronic myeloid leukemia (CML) or chronic lymphocytic leukemia;
(6) acute lymphoblastic leukemia, B-cell acute lymphoblastic leukemia, or T-cell acute lymphoblastic leukemia; or (j) multiple myeloma; optionally, said multiple myeloma. The tumor is B-cell myeloma;
Optionally, the subject has or is undergoing one or more additional cancer therapies, and/or the subject is in need of regenerative medicine.
The pharmaceutical composition.

A cell, tissue, or biological sample is administered to an effective amount of a compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, or copolymer thereof. 16. A method comprising contacting with a crystal, tautomer, stereoisomer, isotopically labeled derivative, or prodrug, or a pharmaceutical composition according to claim 15,
said contacting is in vitro or ex vivo;
Optionally, said cells are
(a) characterized by one or more embryonic, pluripotent, or adult stem cell properties; and/or (b) cancer stem cells, embryonic stem cells, induced pluripotent stem cells, neural stem cells, differentiated cancer cells; or adult stem cells; and/or optionally, said contacting comprises:
(i) reducing one or more embryonic or adult stem cell properties of said cells;
(ii) reducing cell viability and/or preventing cell proliferation;
(iii) killing said cells;
(iv) inhibiting tumor growth;
(v) prevent metastasis;
(vi) differentiating one or more cells; and/or (vii) regenerating one or more cells;
Said method.

An effective amount of the compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, or steric thereof, is administered to cells. 16. A method comprising killing with an isomer, isotopically labeled derivative, or prodrug, or a pharmaceutical composition according to claim 15,
said killing is in vitro or ex vivo;
Optionally, said cells are
(a) characterized by one or more embryonic or adult stem cell properties; and/or (b) cancer stem cells, embryonic stem cells, induced pluripotent stem cells, neural stem cells, adult stem cells, or differentiated cancer cells. And;
Optionally, said killing reduces one or more embryonic or adult stem cell properties of said cells.
Said method.

The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15;
(a) inhibiting NAMPT in the subject;
(b) inhibiting the NAMPT pathway in the subject;
(c) reducing NAMPT signaling in the subject;
(d) inhibiting the production of nicotinamide mononucleotide in the subject;
(e) inhibiting the production of nicotinamide adenine dinucleotide in the subject;
(f) reducing inflammatory activity in the subject;
(g) reducing inflammatory cell infiltration in the subject;
(h) reducing cell proliferation in a subject; or (i) a pharmaceutical composition for use in reducing cellular metabolic activity or condition in a subject.

(a) inhibiting NAMPT in a cell, tissue, or biological sample;
(b) inhibiting the NAMPT pathway in a cell, tissue, or biological sample;
(c) reducing NAMPT signaling in a cell, tissue, or biological sample;
(d) inhibiting the production of nicotinamide adenine dinucleotide in a cell, tissue, or biological sample;
(e) inhibiting the production of nicotinamide mononucleotide in a cell, tissue, or biological sample;
(f) reduce inflammatory activity in cells, tissues, or biological samples;
(g) reduce inflammatory cell infiltration in cells, tissues, or biological samples;
(h) reducing cellular metabolic activity or condition in a cell, tissue, or biological sample; or (i) a method of reducing cell proliferation in a cell, tissue, or biological sample, comprising: , or a biological sample as a compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, or tautomer thereof. , a stereoisomer, an isotopically labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15, wherein said contacting is performed in vitro or ex vivo.

The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative or prodrug; or a pharmaceutical composition according to claim 15; and said compound, a pharmaceutically acceptable salt, solvate, hydrate, polymorph, co-crystal, tautomer, steric A kit comprising instructions for using the isomer, isotopically labeled derivative, prodrug, or pharmaceutical composition.

A pharmaceutical composition for use in treating a disease or disorder in a subject, the composition comprising:
The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15;
Optionally, the disease or disorder is heart failure, dilated cardiomyopathy, pain, inflammation, acute distress syndrome, ventilator-induced lung injury, graft versus host disease (GCDH), pneumonia, pneumonitis, severe acute distress. Syndrome, arthritis, acute lung injury, colitis, inflammatory bowel disease (IBD), diabetes, obesity, axonal degeneration, impaired tissue repair, asthma, chronic obstructive pulmonary disease (COPD), osteoarthritis, osteoporosis, fibrosis Associated with sexual diseases, skin diseases, psoriasis, atopic dermatitis, UV-induced skin damage, autoimmune diseases, Alzheimer's disease, stroke, atherosclerosis, restenosis, glomerulonephritis, cachexia, and infectious diseases Inflammation, vascular inflammation, atherothrombotic disease, acquired immune deficiency syndrome (AIDS), adult respiratory distress syndrome, ataxia telangiectasia, atherogenic inflammatory disease, cardiovascular disorder, cerebrovascular disorder, acute coronary syndrome , polycystic ovary syndrome, preeclampsia, sepsis, septic shock, intrauterine infection, Crohn's disease (CD), ulcerative colitis (UC), neurodegenerative disorders, COVID-19, pulmonary inflammation, coronavirus an infectious disease, or a tumor; and/or optionally, said disease or disorder is
(a) modulating NAMPT in a subject;
(b) modulating the NAMPT pathway in the subject;
(c) modulating NAMPT signaling in the subject;
(d) modulating the production of nicotinamide mononucleotide in the subject;
(e) modulating the production of nicotinamide adenine dinucleotide in the subject;
(f) modulating inflammatory activity in the subject; or (g) being treated by modulating cellular metabolic activity or condition in the subject;
The pharmaceutical composition.

The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15;
(a) modulate NAMPT in the subject;
(b) modulating the NAMPT pathway in the subject;
(c) modulating NAMPT signaling in the subject;
(d) modulating the production of nicotinamide mononucleotide in the subject;
(e) modulating the production of nicotinamide adenine dinucleotide in the subject;
(f) modulating inflammatory activity in a subject; or (g) a pharmaceutical composition for use in modulating cellular metabolic activity or condition in a subject.

A pharmaceutical composition for use in contacting a cell, tissue, or biological sample, the composition comprising:
The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15;
Optionally, said cells are
(a) characterized by one or more embryonic, pluripotent, or adult stem cell properties; and/or (b) cancer stem cells, embryonic stem cells, induced pluripotent stem cells, neural stem cells, differentiated cancer cells; or adult stem cells; and/or optionally, said contacting comprises:
(i) reducing one or more embryonic or adult stem cell properties of said cells;
(ii) reducing cell viability and/or preventing cell proliferation;
(iii) killing said cells;
(iv) inhibiting tumor growth;
(v) prevent metastasis;
(vi) differentiating one or more cells; and/or (vii) regenerating one or more cells;
The pharmaceutical composition.

A pharmaceutical composition for use in killing cells, the composition comprising:
The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15;
Optionally, said cells are
(a) characterized by one or more embryonic or adult stem cell properties; and/or (b) cancer stem cells, embryonic stem cells, induced pluripotent stem cells, neural stem cells, adult stem cells, or differentiated cancer cells. And;
Optionally, said killing reduces one or more embryonic or adult stem cell properties of said cells.
The pharmaceutical composition.

The compound according to any one of claims 1 to 14, or a pharmaceutically acceptable salt, solvate, hydrate, polymorph, cocrystal, tautomer, stereoisomer, isotope thereof a labeled derivative, or a prodrug, or a pharmaceutical composition according to claim 15;
(a) inhibiting NAMPT in a cell, tissue, or biological sample;
(b) inhibiting the NAMPT pathway in a cell, tissue, or biological sample;
(c) reducing NAMPT signaling in a cell, tissue, or biological sample;
(d) inhibiting the production of nicotinamide adenine dinucleotide in a cell, tissue, or biological sample;
(e) inhibiting the production of nicotinamide mononucleotide in a cell, tissue, or biological sample;
(f) reduce inflammatory activity in cells, tissues, or biological samples;
(g) reduce inflammatory cell infiltration in cells, tissues, or biological samples;
(h) reduce cellular metabolic activity or condition in a cell, tissue, or biological sample; or (i) a pharmaceutical composition for use in reducing cell proliferation in a cell, tissue, or biological sample. thing.