4-{[1-(1-Benzyl-2-oxo-ethylcarbamoyl)-3-methyl-butylcarbamoyl]-[3-(1-carboxy-2-phenyl-ethyl)-ureido]-methyl}-tetrahydro-pyrimidin-2-ylidene-ammonium (chymostatin)

ID: ALA247767

Cas Number: 9076-44-2

PubChem CID: 443119

Max Phase: Preclinical

Molecular Formula: C31H41N7O6

Molecular Weight: 607.71

Molecule Type: Small molecule

Names and Identifiers

Synonyms: Chymostatin | Chymostatin|CHEMBL247767|9076-44-2|C11308|AC1L9E22|DB01683|SCHEMBL8259564|BDBM87059|CHEBI:510447|BDBM222139|BDBM50288847|(2S)-2-[[(1S)-1-(2-amino-1,4,5,6-tetrahydropyrimidin-6-yl)-2-[[(1S)-1-[[(1S)-1-benzyl-2-oxo-ethyl]carbamoyl]-3-methyl-butyl]amino]-2-oxo-ethyl]carbamoylamino]-3-phenyl-propanoic acid|(2S)-2-[[(1S)-2-[[(1S)-1-[[(1S)-1-benzyl-2-oxo-ethyl]carbamoyl]-3-methyl-butyl]amino]-1-(2-iminohexahydropyrimidin-4-yl)-2-oxo-ethyl]carbamoylamino]-3-phenyl-propanoic acid|[(S)-1-CaShow More⌵

Canonical SMILES:  CC(C)C[C@H](NC(=O)[C@@H](NC(=O)N[C@@H](Cc1ccccc1)C(=O)O)C1CCNC(=N)N1)C(=O)N[C@H](C=O)Cc1ccccc1

Standard InChI:  InChI=1S/C31H41N7O6/c1-19(2)15-24(27(40)34-22(18-39)16-20-9-5-3-6-10-20)35-28(41)26(23-13-14-33-30(32)36-23)38-31(44)37-25(29(42)43)17-21-11-7-4-8-12-21/h3-12,18-19,22-26H,13-17H2,1-2H3,(H,34,40)(H,35,41)(H,42,43)(H3,32,33,36)(H2,37,38,44)/t22-,23?,24-,25-,26-/m0/s1

Standard InChI Key:  MRXDGVXSWIXTQL-HYHFHBMOSA-N

Molfile:  

     RDKit          2D

 44 46  0  0  0  0  0  0  0  0999 V2000
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    2.9917   -8.2917    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
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    0.8500   -8.7042    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    2.9917   -5.8250    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7042   -8.7042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5833   -8.7042    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2958   -8.2917    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0083   -8.7042    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.1375   -8.7042    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.5667   -5.8250    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
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    0.8542   -6.2292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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   -2.0083   -7.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5667   -7.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.4042  -10.2250    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.0083   -6.2292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7208   -7.4667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    7.2792   -7.4667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    5.3417   -9.9667    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
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    7.9917   -7.0542    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.2750   -5.8167    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.9917   -6.2292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.4333   -6.2292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  2  1  1  0
  3  4  1  0
  4  8  1  0
  5  9  1  0
  6 11  1  0
  7  2  1  0
  1  8  1  1
  9  1  1  0
 10  3  2  0
 11  7  1  0
 12  5  1  0
 13 12  1  0
 14 13  1  0
 15  6  1  0
 16 27  1  0
 17  2  2  0
 18  5  2  0
 19  6  2  0
 13 20  1  6
 21 14  2  0
 11 22  1  6
 23 15  1  0
 24 26  2  0
 25  8  1  0
 26 23  1  0
 27 25  1  0
 28 14  1  0
 23 29  1  1
 30 20  1  0
 31 29  1  0
 32 22  1  0
 33 30  2  0
 34 30  1  0
 35 31  1  0
 36 31  2  0
 37 32  1  0
 38 32  1  0
 39 34  2  0
 40 33  1  0
 41 36  1  0
 42 35  2  0
 43 41  2  0
 44 39  1  0
  3 16  1  0
 40 44  2  0
 42 43  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA247767

   CHYMOSTATIN

Molecule Features

Natural Product: Yes

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 607.71

Molecular Weight (Monoisotopic): 607.3118

AlogP: 0.69

#Rotatable Bonds: 15

Polar Surface Area: 201.61

Molecular Species: ZWITTERION

HBA: 6

HBD: 8

#RO5 Violations: 2

HBA (Lipinski): 13

HBD (Lipinski): 8

#RO5 Violations (Lipinski): 3

CX Acidic pKa: 3.76

CX Basic pKa: 10.99

CX LogP: -0.39

CX LogD: -0.39

Aromatic Rings: 2

Heavy Atoms: 44

QED Weighted: 0.14

Np Likeness Score: 0.40

References

1. Akahoshi F, Ashimori A, Sakashita H, Yoshimura T, Imada T, Nakajima M, Mitsutomi N, Kuwahara S, Ohtsuka T, Fukaya C, Miyazaki M, Nakamura N..  (2001)  Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic alpha-keto heterocycles as novel inhibitors of human chymase.,  44  (8): [PMID:11312927] [10.1021/jm000496v]

2. Akahoshi F, Ashimori A, Sakashita H, Yoshimura T, Eda M, Imada T, Nakajima M, Mitsutomi N, Kuwahara S, Ohtsuka T, Fukaya C, Miyazaki M, Nakamura N..  (2001)  Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic difluoromethylene ketones as novel inhibitors of human chymase.,  44  (8): [PMID:11312928] [10.1021/jm000497n]

3. Shuttleworth SJ, Nasturica D, Gervais C, Siddiqui MA, Rando RF, Lee N..  (2000)  Parallel synthesis of isatin-based serine protease inhibitors.,  10  (22): [PMID:11086715] [10.1016/s0960-894x(00)00523-0]

4. Tanaka T, Muto T, Maruoka H, Imajo S, Fukami H, Tomimori Y, Fukuda Y, Nakatsuka T..  (2007)  Identification of 6-substituted 4-arylsulfonyl-1,4-diazepane-2,5-diones as a novel scaffold for human chymase inhibitors.,  17  (12): [PMID:17419055] [10.1016/j.bmcl.2007.03.038]

5. Mabkhot YN, Barakat A, Yousuf S, Choudhary MI, Frey W, Ben Hadda T, Mubarak MS..  (2014)  Substituted thieno[2,3-b]thiophenes and related congeners: Synthesis, β-glucuronidase inhibition activity, crystal structure, and POM analyses.,  22  (23): [PMID:25245672] [10.1016/j.bmc.2014.08.014]

6. Al-Awadhi FH, Gao B, Rezaei MA, Kwan JC, Li C, Ye T, Paul VJ, Luesch H..  (2018)  Discovery, Synthesis, Pharmacological Profiling, and Biological Characterization of Brintonamides A-E, Novel Dual Protease and GPCR Modulators from a Marine Cyanobacterium.,  61  (14): [PMID:30015488] [10.1021/acs.jmedchem.8b00885]

7. Chen QY, Luo D, Seabra GM, Luesch H..  (2020)  Ahp-Cyclodepsipeptides as tunable inhibitors of human neutrophil elastase and kallikrein 7: Total synthesis of tutuilamide A, serine protease selectivity profile and comparison with lyngbyastatin 7.,  28  (23.0): [PMID:33002682] [10.1016/j.bmc.2020.115756]

Source

Source(1):

• Scientific Literature